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Sample records for olanzapine long-acting injection

  1. Long-acting injectable antipsychotics: focus on olanzapine pamoate

    Directory of Open Access Journals (Sweden)

    JP Lindenmayer

    2010-05-01

    Full Text Available JP LindenmayerDepartment of Psychiatry, New York University School of Medicine, New York NY, USAAbstract: Medication non-adherence in patients with schizophrenia continues to be a significant problem and threatens successful treatment outcomes. Medication non-adherence is often associated with negative consequences, including symptom exacerbation, more frequent emergency room visits, re-hospitalizations and relapse. Long-acting injectable (LAI forms of antipsychotics allow for rapid identification of non-adherence, obviate the need for the patient to take the medication on a daily basis and increase adherence to some significant degree. Eli Lilly has developed a long-acting depot formulation of olanzapine, olanzapine pamoate, which has recently been approved by the FDA for the US market, and which will be reviewed here. Olanzapine LAI appears to be an effective antipsychotic at dosages of 210 mg every 2 weeks, 300 mg every 2 weeks and 405 mg every 4 weeks in patients with acute schizophrenia, and at 150 mg every 2 weeks, 300 mg every 2 weeks and at 405 mg every 4 weeks for the maintenance treatment of stable patients. Oral supplementation appears not to be needed, particularly not at the onset of treatment with the LAI as is necessary with risperidone LAI. Its efficacy is in general comparable to the efficacy seen with oral olanzapine at a corresponding dose. The side effect profile is also comparable to the side effects observed with oral olanzapine, including lower rates of extrapyramidal symptoms, prolactin elevation and cardiovascular side effects, but significant metabolic effects. The latter include significant weight gain, lipid abnormalities and glucose dysregulation. While the injection site adverse events are overall mild, the most significant serious adverse event is the post-injection delirium sedation syndrome (PDSS. While rare, this syndrome results from inadvertent intravascular injection of olanzapine LAI and can cause a range of

  2. Long-term functional improvements in the 2-year treatment of schizophrenia outpatients with olanzapine long-acting injection

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    Ascher-Svanum H

    2014-06-01

    Full Text Available Haya Ascher-Svanum,1 Diego Novick,2,3 Josep Maria Haro,4 Jordan Bertsch,4 David McDonnell,1 Holland Detke11Eli Lilly and Company, Indianapolis, IN, USA; 2Eli Lilly and Company, Windlesham, Surrey, UK; 3Departament de Psiquiatria, Universitat Autonoma de Barcelona, Spain; 4Parc Sanitari Sant Joan de Déu, Centro de Investigación Biomédica en Red en el Área de Salud Mental, Universitat de Barcelona, Barcelona, SpainBackground: Little is known about the long-term changes in the functioning of schizophrenia patients receiving maintenance therapy with olanzapine long-acting injection (LAI, and whether observed changes differ from those seen with oral olanzapine.Methods: This study describes changes in the levels of functioning among outpatients with schizophrenia treated with olanzapine-LAI compared with oral olanzapine over 2 years. This was a secondary analysis of data from a multicenter, randomized, open-label, 2-year study comparing the long-term treatment effectiveness of monthly olanzapine-LAI (405 mg/4 weeks; n=264 with daily oral olanzapine (10 mg/day; n=260. Levels of functioning were assessed with the Heinrichs–Carpenter Quality of Life Scale. Functional status was also classified as “good”, “moderate”, or “poor”, using a previous data-driven approach. Changes in functional levels were assessed with McNemar’s test and comparisons between olanzapine-LAI and oral olanzapine employed the Student’s t-test. Results: Over the 2-year study, the patients treated with olanzapine-LAI improved their level of functioning (per Quality of Life total score from 64.0–70.8 (P<0.001. Patients on oral ­olanzapine also increased their level of functioning from 62.1–70.1 (P<0.001. At baseline, 19.2% of the olanzapine-LAI-treated patients had a “good” level of functioning, which increased to 27.5% (P<0.05. The figures for oral olanzapine were 14.2% and 24.5%, respectively (P<0.001. Results did not significantly differ between

  3. Schizophrenia symptoms and functioning in patients receiving long-term treatment with olanzapine long-acting injection formulation

    DEFF Research Database (Denmark)

    Peuskens, Joseph; Porsdal, Vibeke; Pecenak, Jan;

    2012-01-01

    ABSTRACT: BACKGROUND: This analysis of pooled data evaluates maintenance treatment outcomes of patients with schizophrenia receiving maintenance treatment with olanzapine long-acting injection (OLAI) by means of a categorical approach addressing the symptomatic and functional status of patients...... at different times. METHODS: Patients were grouped into 5 categories at baseline, 6 months, and 12 months. Shifts between categories were assessed for individual patients and factors associated with improvement were analyzed. 1182 patients from 3 clinical trials were included in the current analysis. RESULTS......: At baseline, 434 (36.8%) patients had minimal Positive and Negative Syndrome Scale (PANSS) symptoms but seriously impaired Heinrich Carpenter's Quality of Life Scale (QLS) functioning; 303 (25.6%) had moderate to severe symptoms and seriously impaired function; 208 (17.6%) had mild to moderate symptoms...

  4. Cost-effectiveness of olanzapine long-acting injection in the treatment of patients with schizophrenia in the United States: a micro-simulation economic decision model.

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    Furiak, Nicolas M; Ascher-Svanum, Haya; Klein, Robert W; Smolen, Lee J; Lawson, Anthony H; Montgomery, William; Conley, Robert R

    2011-04-01

    To compare, from the perspective of third-party payers in the United States health care system, the cost-effectiveness of olanzapine long-acting injection (LAI, depot) with alternative antipsychotic agents including risperidone-LAI, paliperidone-LAI, haloperidol-LAI, and oral olanzapine, in the treatment of patients with schizophrenia who have been non-adherent or partially adherent with oral antipsychotics. A 1-year micro-simulation economic decision model was developed to simulate the dynamics of usual care of patients with schizophrenia who continue, discontinue, switch, or restart their medication. The model uses a range of clinical and cost parameters including adherence levels, relapse with and without hospitalization, quality-adjusted life years (QALYs), treatment discontinuation rates by reason, treatment-emergent adverse events, suicide, health care resource utilization, and direct health care costs. Published medical literature and a clinical expert panel were used to develop baseline model assumptions. Key model outputs include annual total direct cost (US$) per treatment and incremental cost-effectiveness values per additional QALY gained. Model results found that the olanzapine-LAI treatment strategy was more effective (greater QALYs) and less costly than risperidone-LAI, paliperidone-LAI, and haloperidol-LAI. In addition, olanzapine-LAI was both more effective and more costly, with an estimated incremental cost/QALY of $26,824 compared to oral olanzapine. The base-case and multiple sensitivity analyses found olanzapine-LAI to remain within acceptable cost-effective ranges (micro-simulation model finds the olanzapine-LAI treatment strategy to result in better effectiveness and to be a cost-effective alternative compared to oral olanzapine and the LAI formulations of risperidone, paliperidone, and haloperidol in the treatment of non-adherent and partially adherent patients with schizophrenia in the United States. A key limitation is the assumption how

  5. Clinical outcomes with olanzapine long-acting injection: impact of the 3-hour observation period on patient satisfaction and well-being

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    Anand E

    2016-10-01

    Full Text Available Ernie Anand,1 Lovisa Berggren,2 John Landry,3 Ágoston Tóth,4 Holland C Detke5 1Neuroscience Medical Affairs, Eli Lilly & Company Ltd, Windlesham, UK; 2Global Statistical Sciences, Lilly Deutschland GmbH, Bad Homburg, Germany; 3Global Statistical Sciences, Eli Lilly Canada Inc., Toronto, ON, Canada; 4Neuroscience, Lilly Hungary, Budapest, Hungary; 5Psychiatry and Pain Disorders, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA Background: The objective of the present analysis is to determine the impact of the 3-hour observation period for olanzapine long-acting injection (LAI on patient satisfaction and well-being by comparing data collected before and after its implementation. Methods: This is a post hoc analysis of patients treated with olanzapine LAI in 1 a 6-month fixed-dose randomized controlled trial and/or 2 a 6-year open-label safety study. This analysis was limited to patients with schizophrenia who were treated with olanzapine LAI consistent with the approved indication and dosing recommendations of the European Union Summary of Product Characteristics (N=966. Of the 966 patients, the analysis further focused only on those patients who received both 1 at least one injection before the implementation of the 3-hour observation period and 2 at least one injection after implementation of the 3-hour observation period (N=487. Patient satisfaction was assessed with the three-item Patient Satisfaction with Medication Questionnaire-Modified. Responses were averaged across all postbaseline visits occurring before (ie, without the implementation of the 3-hour observation period and across all postbaseline visits occurring after (ie, with the implementation of the 3-hour observation period. In addition, the rate of postinjection delirium/sedation syndrome events was calculated. Results: There was no meaningful change after implementation of the 3-hour observation period in satisfaction (before: mean [SD] =4.0 [1.02] and

  6. Cost effectiveness of paliperidone palmitate versus risperidone long-acting injectable and olanzapine pamoate for the treatment of patients with schizophrenia in Sweden.

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    Mehnert, Angelika; Nicholl, Deborah; Pudas, Hanna; Martin, Monique; McGuire, Alistair

    2012-01-01

    To model the cost effectiveness of paliperidone palmitate (paliperidone long-acting injectable; PLAI), a new once-monthly long-acting antipsychotic therapy, compared with risperidone long-acting injectable (RLAI) and olanzapine pamoate (OLAI), in multi-episode patients (two or more relapses) with schizophrenia in Sweden. A Markov decision analytic model was developed to simulate the history of a cohort of multi-episode patients transitioning through different health states on a monthly basis over a 5-year time horizon from the perspective of the Swedish healthcare system. Therapeutic strategies consisted of starting treatment with RLAI (mean dose 37.5 mg every 2 weeks), PLAI (mean dose 75 mg equivalent (eq.) every month) or OLAI (150 mg every 2 weeks or 300 mg every 4 weeks). Probability of relapse, level of adherence, side-effects (extrapyramidal symptoms, tardive dyskinesia, weight gain and diabetes) and treatment discontinuation (switch) were derived from long-term observational data when feasible. Incremental cost-effectiveness outcomes, discounted at 3% annually, included cost per quality-adjusted life-year (QALY) and cost per relapse avoided (expressed in 2009 Swedish Krona SEK). Relative to RLAI and OLAI, PLAI is economically dominant: more effective (additional QALYs, less relapses) and less costly treatment option over a 5-year time horizon. The results were robust when tested in sensitivity analysis. The impact of once-monthly treatment on adherence levels is not yet known, and not all variables that could impact on real-world outcomes and costs were included in this model. PLAI was cost saving from a Swedish payer perspective compared with RLAI and OLAI in the long-term treatment of multi-episode (two or more relapses) schizophrenia patients.

  7. Schizophrenia symptoms and functioning in patients receiving long-term treatment with olanzapine long-acting injection formulation: a pooled analysis

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    Peuskens Joseph

    2012-08-01

    Full Text Available Abstract Background This analysis of pooled data evaluates treatment outcomes of patients with schizophrenia receiving maintenance treatment with olanzapine long-acting injection (OLAI by means of a categorical approach addressing the symptomatic and functional status of patients at different times. Methods Patients were grouped into 5 categories at baseline, 6 months, and 12 months. Shifts between categories were assessed for individual patients and factors associated with improvement were analyzed. 1182 patients from 3 clinical trials were included in the current analysis. Results At baseline, 434 (36.8% patients had minimal Positive and Negative Syndrome Scale (PANSS symptoms but seriously impaired Heinrich Carpenter’s Quality of Life Scale (QLS functioning; 303 (25.6% had moderate to severe symptoms and seriously impaired function; 208 (17.6% had mild to moderate symptoms but good functioning, and 162 (13.7% had minimal symptoms and good functioning. Baseline category was significantly associated with Clinical Global Impression – Severity (CGI-S, extrapyramidal symptoms, working status, age, and number of previous episodes. The majority of all patients starting OLAI treatment maintained or improved (62% at 6 months and 52% at 12 months their symptom and functioning levels on OLAI maintenance treatment. Less than 8% of the patients showed worsening of symptoms or functioning. An improvement in category was associated with high PANSS positive and low CGI-S scores at baseline. Conclusions We present evidence that a composite assessment of schizophrenic patients including symptom severity and functioning is helpful in the evaluation of maintenance treatment outcomes. This approach could also be useful for the assessment of treatment options in clinical practice. The trials from which data are reported here were registered on clinicaltrials.gov as NCT00088491, NCT00088465, and NCT00320489.

  8. Postinjection Delirium/Sedation Syndrome with Olanzapine Depot Injection

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    Sarangula, Sadhvi Mythili; Mythri, Starlin Vijay; Sanjay, Y.; Reddy, M. S.

    2016-01-01

    After 1 year of introduction of olanzapine long-acting injectable (LAI) in India, many psychiatrists believe that it is a very affordable, well-tolerated, and effective second generation long-acting antipsychotic depot compared to not well tolerated but cheap first generation antipsychotic depots and to other second generation depots which are costly. However, reports of its possible adverse events in clinical settings are not yet published. We report what probably might be the first case of postinjection delirium/sedation syndrome (PDSS) in India. Although the occurrence is uncommon, incorrect understanding of this event may hinder the future use of the potentially useful olanzapine LAI. We review the available literature on the proposed diagnostic guidelines, mechanism of this event, precautions, and management of PDSS. PMID:27570354

  9. Long-Acting Injectable Antipsychotics in Children and Adolescents.

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    Lytle, Sarah; McVoy, Molly; Sajatovic, Martha

    2017-02-01

    While a number of articles have reviewed the use of long-acting injectable antipsychotics (LAIs) in first-episode psychosis, there has been extremely limited focus on LAIs in children and adolescents. This review of the literature evaluated use of LAIs in children and youth under the age of 18. We conducted a comprehensive search of the PubMed, PsychINFO, CINAHL, and EMBASE databases using keywords related to LAIs, children, and psychiatric conditions, including schizophrenia, bipolar disorder, and schizoaffective disorder. Reports were included if they were in English, conducted between 1971 and 2015, and reported on use of LAIs in individuals less than the age of 18. The search identified seven reports including one open-label trial, three case reports, and three case series. No controlled trials were found. Sample sizes ranged from 1 to 19 with a total of 36 individuals in all cases combined. Mean sample age was 12.1 ± 2.2 in the open-label trial and calculated to be 14.9 ± 1.5 in the remainder of the reports. Most patients (80.6%) were boys. Primary diagnoses included bipolar I disorder (n = 18; 50%), schizophrenia (n = 7; 19.4%), and bipolar spectrum disorders (n = 6; 16.6%). The LAIs used were risperidone long-acting injection (n = 24; 66.7%), paliperidone palmitate (n = 8; 22.2%), fluphenazine decanoate (n = 1; 2.8%), aripiprazole extended-release injectable (n = 1; 2.8%), zuclopenthixol decanoate (n = 1; 2.8%), and olanzapine extended release (n = 1; 2.8%). Most cases reported clinical improvement and the majority of individuals (n = 14; 82.4%) were reported to tolerate the medication well. The most common side effects were weight gain (mean 5.7 ± 4.1 kg in the open-label trial), tremor (n = 2; 5.6%), and oculogyric crisis (n = 2; 5.6%). This literature review suggests that LAI use in youth with serious mental illness may improve clinical outcomes and adherence. Side effects of LAIs among

  10. Deltoid injections of risperidone long-acting injectable in patients with schizophrenia.

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    Quiroz, Jorge A; Rusch, Sarah; Thyssen, An; Palumbo, Joseph M; Kushner, Stuart

    2011-06-01

    Risperidone long-acting injectable was previously approved for treatment of schizophrenia as biweekly injections in the gluteal muscle only. We present data on local injection-site tolerability and safety of risperidone long-acting injectable and comparability of systemic exposure of deltoid versus gluteal injections. Risperidone long-acting injectable was administered in an open-label, single-dose, two-way crossover study, with patients randomized to receive either 25mg gluteal/37.5mg deltoid crossover in two treatment periods or 50mg gluteal/50mg deltoid injections crossover; each treatment period was separated by an 85-day observation period (Study 1) and an open-label, multiple-dose study (4 sequential 37.5mg or 50mg deltoid injections every 2 weeks) (Study 2). The pharmacokinetic results from both the studies have already been published. In Study 1 (n=170), the majority of patients had no local injection-site findings, based on investigator and patient-rated evaluations. In Study 2 (n=53), seven of the 51 patients who received at least two deltoid injections discontinued (primary endpoint). However, none of the discontinuations were due to injection-site related reasons. The 90-percent upper confidence limit of the true proportion of injection-site issue withdrawals was 5.7 percent. No moderate or severe injection-site reactions were reported. Intramuscular injections via the deltoid and gluteal sites are equivalent routes of administration of risperidone long-acting injectable with respect to local injection-site tolerability. The overall safety and tolerability profile of risperidone long-acting injectable was comparable when administered as an intramuscular injection in the deltoid (37.5mg and 50mg) and gluteal (25mg and 50mg) sites.

  11. Efficacy of Long-Acting Injectable Antipsychotics in Adolescents.

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    Pope, Stephanie; Zaraa, Solomon G

    2016-05-01

    The number of long-acting injectable antipsychotics (LAIA) has increased in recent years. The safety and efficacy of that treatment are not established in children. This study aims to address this gap of information by studying such treatments in a case series. This retrospective chart review of patients identified by the investigators at an academic acute inpatient psychiatric unit included all patients from the past 24 months who required new initial treatment with LAIA. This study included a case series of the nine patients along with Clinical Global Impression-Severity (CGI-S) scores from admission and discharge and Clinical Global Impression-Improvement (CGI-I) scores. Other observations included the presentation of primary psychiatric diagnosis, psychiatric and medical comorbidities, age, sex, previous and LAIA psychiatric medications, reasoning for LAIA treatment, adverse events, CGI-S and CGI-I scores, and outpatient resources utilized to continue treatment. The case series included two females and seven males within the ages of 14-17 years. Of those patients, five were treated with paliperidone palmitate, one treated with risperidone, one treated with fluphenazine, and one treated with aripiprazole. Primary psychiatric diagnosis of the patients in the case series included five with schizophrenia, one with schizoaffective disorder, one with bipolar affective disorder-type I, one with bipolar affective disorder-not otherwise specified, and one with mood disorder-not otherwise specified. In all nine cases, noncompliance was a consideration in treatment with LAIA. Frequent running away and severity of illness were also considerations in one case each. All of the patients required community resources with injectable services. This study describes initiation of treatment with LAIA in 14-17-year olds in an acute inpatient psychiatric unit with serious mental illness. This study also demonstrates the need for outpatient community resources with the ability to

  12. Risperidone Long-Acting Injections: Successful Alternative Deltoid Muscle Injections for Refractory Schizophrenia

    OpenAIRE

    Saxena, Arjun; Grace, Jeffery; Olympia, Josie L.; Trigoboff, Eileen; Watson, Thomas; Cushman, Sharon; Newcomer, David

    2008-01-01

    Treatment-resistant paranoid schizophrenia is often addressed with long-term intramuscular preparations of conventional antipsychotics (haloperidol and fluphenazine), which can be associated with the development of painful, lumpy nodules at the injection site. In this article, we present a case example of a 58-year-old male patient with paranoid schizophrenia who was treated with risperidone long-acting injection given into the deltoid muscle instead of the US Food and Drug Administration (FD...

  13. Second-generation long-acting injectable antipsychotics in schizophrenia: patient functioning and quality of life

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    Montemagni C

    2016-04-01

    Full Text Available Cristiana Montemagni,1,2 Tiziana Frieri,1,2 Paola Rocca1,2 1Department of Neuroscience, Unit of Psychiatry, University of Turin, 2Department of Mental Health, Azienda Sanitaria Locale (ASL Torino 1 (TO1, Azienda Ospedaliero-Universitaria (AOU Città della Salute e della Scienza di Torino, Turin, Italy Abstract: Long-acting injectable antipsychotics (LAIs were developed to make treatment easier, improve adherence, and/or signal the clinician when nonadherence occurs. Second-generation antipsychotic LAIs (SGA-LAIs combine the advantages of SGA with a long-acting formulation. The purpose of this review is to evaluate the available literature concerning the impact of SGA-LAIs on patient functioning and quality of life (QOL. Although several studies regarding schizophrenia patients’ functioning and QOL have been performed, the quantity of available data still varies greatly depending on the SGA-LAI under investigation. After reviewing the literature, it seems that SGA-LAIs are effective in ameliorating patient functioning and/or QOL of patients with schizophrenia, as compared with placebo. However, while methodological design controversy exists regarding the superiority of risperidone LAI versus oral antipsychotics, the significant amount of evidence in recently published research demonstrates the beneficial influence of risperidone LAI on patient functioning and QOL in stable patients and no benefit over oral treatment in unstable patients. However, the status of the research on SGA-LAIs is lacking in several aspects that may help physicians in choosing the correct drug therapy. Meaningful differences have been observed between SGA-LAIs in the onset of their clinical efficacy and in the relationships between symptoms and functioning scores. Moreover, head-to-head studies comparing the effects of SGA-LAIs on classical measures of psychopathology and functioning are available mainly on risperidone LAI, while those comparing olanzapine LAI with other

  14. Long-Acting Diclofenac Ester Prodrugs for Joint Injection

    DEFF Research Database (Denmark)

    Mertz, Nina; Larsen, Susan Weng; Kristensen, Jesper

    2016-01-01

    A prodrug approach for local and sustained diclofenac action after injection into joints based on ester prodrugs having a pH-dependent solubility is presented. Inherent ester prodrug properties influencing the duration of action include their pH-dependent solubility and charge state, as well...... as susceptibility to undergo esterase facilitated hydrolysis. In this study, physicochemical properties and pH rate profiles of 3 diclofenac ester prodrugs differing with respect to the spacer carbon chain length between the drug and the imidazole-based promoiety were determined and a rate equation for prodrug...... degradation in aqueous solution in the pH range 1-10 was derived. In the pH range 6-10, the prodrugs were subject to parallel degradation to yield diclofenac and an indolinone derivative. The prodrug degradation was found to be about 6-fold faster in 80% (vol/vol) human plasma as compared to 80% (vol...

  15. Long-acting injectable antipsychotics: evidence of effectiveness and use.

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    Manchanda, Rahul; Chue, Pierre; Malla, Ashok; Tibbo, Phil; Roy, Marc-André; Williams, Richard; Iyer, Srividya; Lutgens, Danyael; Banks, Nicola

    2013-05-01

    Objectif : Examiner les données probantes sur le rôle des antipsychotiques (AP) injectables à action prolongée (IAP), spécialement ceux de la deuxième génération (APDG) IAP, dans le traitement de la schizophrénie et discuter des taux d’utilisation des IAP au Canada. Méthode : Une recherche des bases de données médicales a été menée dans la littérature publiée (1995–2012) sur les effets des IAP sur les domaines de la rémission, l’observance, la rechute, et l’hospitalisation. Les résultats obtenus des essais randomisés contrôlés (ERC), des revues systématiques, des méta-analyses, et des études d’observation à grande échelle ont été inclus. Les données de consensus des experts ont aussi été sollicitées en ce qui concerne l’utilisation des IAP dans un contexte canadien. Résultats : Bien que l’efficacité des IAP, comparativement aux placebos, soit bien établie, les données probantes des ERC sont équivoques quant à un avantage spécifique des APDG IAP, comparativement aux médicaments oraux, ce qui est probablement attribuable aux difficultés de mener de tels ERC. Les données probantes d’études moins rigoureuses sur le plan méthodologique et de la pratique clinique suggèrent certains avantages pour atteindre et maintenir la rémission, le risque de rechute, et l’hospitalisation. Le taux d’utilisation des IAP (AP de première génération et APDG), tiré des études publiées sur les patients externes, est faible à 6,3 % au Canada, comparativement à 15 % à 80 % dans le monde. Cependant, le taux d’utilisation est relativement élevé dans des programmes spécifiques de psychose précoce et conjointement avec les ordonnances de traitement en milieu communautaire au Canada. Conclusions : Les IAP sont au moins aussi efficaces que les AP par voie orale dans le traitement des troubles psychotiques. Les IAP peuvent présenter des avantages spécifiques pour les patients qui démontrent une non-observance secr

  16. Comparison of SGA Oral Medications and a Long-Acting Injectable SGA : The PROACTIVE Study

    NARCIS (Netherlands)

    Buckley, Peter F.; Schooler, Nina R.; Goff, Donald C.; Hsiao, John; Kopelowicz, Alexander; Lauriello, John; Manschreck, Theo; Mendelowitz, Alan J.; Miller, Del D.; Severe, Joanne B.; Wilson, Daniel R.; Ames, Donna; Bustillo, Juan; Mintz, Jim; Kane, John M.; de Jong, Corina

    2015-01-01

    Until relatively recently, long-acting injectable (LAI) formulations were only available for first-generation antipsychotics and their utilization decreased as use of oral second-generation antipsychotics (SGA) increased. Although registry-based naturalistic studies show LAIs reduce rehospitalizatio

  17. Olanzapine

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    ... bipolar disorder (manic depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods) in ... Olanzapine may cause side effects. Tell your doctor if any of these ... difficulty walking constipation weight gain dry mouth pain in arms, legs, ...

  18. Hospitalizations and economic analysis in psychotic patients with paliperidone palmitate long-acting injection.

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    Mesones-Peral, Jesús E; Gurillo-Muñoz, Pedro; Sánchez-Sicilia, Mari Paz; Miller, Adam; Griñant-Fernández, Alejandra

    Prevent hospitalizations in psychotic disorders is an important aim, so long-acting antipsychotic is a good option that can control better the correct adherence. Moreover, in the current economic context pharmacoeconomic studies are necessary. We estimate the effect in prevention of paliperidone palmitate long-acting injection (PP-LAI) and calculate the economic cost in the 12 months preceding the start of treatment with PP-LAI and 12 months later. Mirror image study of 71 outpatients diagnosed with psychotic disorders and treated with PP-LAI. In a first analysis, we measured along one year: number of hospitalizations/year, number of hospitalization in days, number of emergency assists/year and if there is antipsychotics associated to long-acting treatment. After this phase, we applied Fees Act of Valencia for economic analysis and estimate of the cost per hospitalization (€ 5,640.41) and hospital emergency (€ 187.61). After one year of treatment with PP-LAI (mean dose=130.65mg/month), we obtained greater numbers in assistance variables: total hospitalizations decrease, 78.8% (P=.009); shortening in hospitalization days, 89.4% (P=.009); abridgement of number of emergency assists, 79.1% (P=.002); decrease of rate of antipsychotics associated to long-acting treatment, 21% (P<.0001); increase in monotherapy, 53.8% (P<.0001). Therefore, after 12 months of treatment with PP-LAI we obtained a reduction in inpatient spending (savings of € 175,766.54) and increased spending on antipsychotics 32% (equivalent to € 151,126.92). PP-LAI can be an effective therapy for the treatment of patients with severe psychotic disorders: improves symptomatic stability and can prevent hospitalizations with cost-effective symptom control. Copyright © 2016 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Risperidone long-acting injection: a review of its long term safety and efficacy

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    Michael K Rainer

    2008-08-01

    Full Text Available Michael K RainerMemory-Clinic and Psychiatric Department, Donauspital, Vienna, AustriaAbstract: A long-acting form of the second-generation antipsychotic drug risperidone is now broadly available for the treatment of schizophrenia and closely related psychiatric conditions. It combines the advantage of previously available depot formulations for first-generation drugs with the favorable characteristics of the modern “atypical” antipsychotics, namely higher efficacy in the treatment of the negative symptoms of schizophrenia and reduced motor disturbances. Published clinical studies show an objective clinical efficacy (as per psychiatric symptom scores and relapse data that exceeds that of oral atypical antipsychotics when patients are switched to the long-acting injectable form, a low incidence of treatment-emergent extrapyramidal side effects, and very good acceptance by patients. Available data for maintenance treatment of bipolar disorder show equivalence with the oral form instead of superiority, but are still limited. As it seems likely that efficacy benefits are mostly due to the fact that the injectable form reduces the demand for patient compliance to one physician visit every 2 weeks instead of self-administration on a daily or twice-daily basis, additional potential could exist in other psychiatric disorders where atypical antipsychotic drugs are of benefit but where patient adherence to treatment schedules is typically low.Keywords: risperidone, schizophrenia, psychotic disorders, patient compliance; delayed-action preparations, injections, intramuscular

  20. The Pharmacokinetics of Second-Generation Long-Acting Injectable Antipsychotics: Limitations of Monograph Values.

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    Lee, Lik Hang N; Choi, Charles; Collier, Abby C; Barr, Alasdair M; Honer, William G; Procyshyn, Ric M

    2015-12-01

    Product monographs (also known by terms such as Summary of Product Characteristics and Highlights of Prescribing Information, depending on the jurisdiction) provide essential information to ensure the safe and effective use of a drug. Medical practitioners often rely on these monographs for guidance on matters related to pharmacokinetics as well as indications, contraindications, clinical pharmacology, and adverse reactions. The clinical and scientific information found within these documents, forming the basis for decision making, are presumed to be derived from well-designed studies. The objective of this review is to examine the source and validity of the pharmacokinetic data used in establishing the half-lives and times to steady-state reported in the product monographs of second-generation long-acting injectable antipsychotics. Thus, we have critically evaluated the clinical trials from which the pharmacokinetic parameters listed in the product monographs were determined. In many cases, the pharmacokinetic information presented in product monographs is of limited use to clinicians wishing to optimize the effectiveness and tolerability of second-generation long-acting injectable antipsychotics. Under such circumstances, off-label prescribing practices may actually produce better clinical outcomes than if decisions were made based on the product monographs alone.

  1. Emerging treatments in the management of bipolar disorder – focus on risperidone long acting injection

    Directory of Open Access Journals (Sweden)

    Wissam El-Hage

    2010-07-01

    Full Text Available Wissam El-Hage1, Simon A Surguladze21Inserm U930 ERL CNRS 3106, Université François Rabelais and Clinique Psychiatrique Universitaire, CHRU de Tours, Tours, France; 2Institute of Psychiatry, King’s College London, UKAbstract: Bipolar disorder is a life-long psychiatric illness characterized by a high frequency of relapses and substantial societal costs. Almost half of the patients are prescribed second generation antipsychotics for treatment of manic states, or as the maintenance therapy. ­Risperidone long acting injection (RLAI as a monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of bipolar I disorder was approved by Food and Drug Administration (FDA in United States in May 2009. In this review we will consider the aspects of pharmacology, pharmacokinetics, metabolism, safety and tolerability, and clinical trials focusing on the efficacy of RLAI in bipolar disorder. The patients’ perspective and attitudes to long-acting injections will also be discussed.Keywords: second generation, antipsychotics, patient attitudes, lithium, valproate, monotherapy

  2. A critical appraisal of paliperidone long-acting injection in the treatment of schizoaffective disorder

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    Chue P

    2016-01-01

    Full Text Available Pierre Chue,1 James Chue2 1Department of Psychiatry, University of Alberta, 2Clinical Trials and Research Program, Edmonton, AB, Canada Abstract: Schizoaffective disorder (SCA is a chronic and disabling mental illness that presents with mixed symptoms of schizophrenia and affective disorders. SCA is recognized as a discrete disorder, but with greater heterogeneity and symptom overlap, leading to difficulty and delay in diagnosis. Although the overall prognosis is intermediate between schizophrenia and mood disorders, SCA is associated with higher rates of suicide and hospitalization than schizophrenia. No treatment guidelines exist for SCA, and treatment is frequently complex, involving off-label use and polypharmacy (typically combinations of antipsychotics, mood stabilizers, and antidepressants. Oral paliperidone extended-release was the first agent to be approved for the treatment of SCA. As in schizophrenia and bipolar disorder, adherence to oral medications is poor, further contributing to suboptimal outcomes. The use of an antipsychotic in a long-acting injection (LAI addresses adherence issues, thus potentially reducing relapse. Paliperidone palmitate represents the LAI formulation of paliperidone. In a long-term, double-blind, randomized, controlled trial of adult patients (n=334; intent-to-treat [ITT] with SCA, paliperidone long-acting injection (PLAI significantly delayed risk of relapse compared to placebo (hazard ratio 2.49, 95% confidence interval, 1.55–3.99; P<0.001. This study demonstrated the efficacy and safety of PLAI when used as either monotherapy or adjunctive therapy for the maintenance treatment of SCA. The results are consistent with a similarly designed study conducted in patients with schizophrenia, which suggests a benefit in the long-term control of not only psychotic but also affective symptoms. No new safety signals were observed. When used in monotherapy, PLAI simplifies treatment by reducing complex

  3. A critical appraisal of paliperidone long-acting injection in the treatment of schizoaffective disorder.

    Science.gov (United States)

    Chue, Pierre; Chue, James

    2016-01-01

    Schizoaffective disorder (SCA) is a chronic and disabling mental illness that presents with mixed symptoms of schizophrenia and affective disorders. SCA is recognized as a discrete disorder, but with greater heterogeneity and symptom overlap, leading to difficulty and delay in diagnosis. Although the overall prognosis is intermediate between schizophrenia and mood disorders, SCA is associated with higher rates of suicide and hospitalization than schizophrenia. No treatment guidelines exist for SCA, and treatment is frequently complex, involving off-label use and polypharmacy (typically combinations of antipsychotics, mood stabilizers, and antidepressants). Oral paliperidone extended-release was the first agent to be approved for the treatment of SCA. As in schizophrenia and bipolar disorder, adherence to oral medications is poor, further contributing to suboptimal outcomes. The use of an antipsychotic in a long-acting injection (LAI) addresses adherence issues, thus potentially reducing relapse. Paliperidone palmitate represents the LAI formulation of paliperidone. In a long-term, double-blind, randomized, controlled trial of adult patients (n=334; intent-to-treat [ITT]) with SCA, paliperidone long-acting injection (PLAI) significantly delayed risk of relapse compared to placebo (hazard ratio 2.49, 95% confidence interval, 1.55-3.99; PPLAI when used as either monotherapy or adjunctive therapy for the maintenance treatment of SCA. The results are consistent with a similarly designed study conducted in patients with schizophrenia, which suggests a benefit in the long-term control of not only psychotic but also affective symptoms. No new safety signals were observed. When used in monotherapy, PLAI simplifies treatment by reducing complex pharmacotherapy and obviating the necessity for daily oral medications. PLAI is the second agent, and the first LAI, to be approved for the treatment of SCA; as an LAI formulation, there is the advantage of improved adherence and

  4. Physician and patient benefit–risk preferences from two randomized long-acting injectable antipsychotic trials

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    Katz EG

    2016-10-01

    Full Text Available Eva G Katz,1 Brett Hauber,2 Srihari Gopal,3 Angie Fairchild,2 Amy Pugh,4 Rachel B Weinstein,3 Bennett S Levitan3 1Janssen Research & Development, LLC, Raritan, NJ, 2RTI Health Solutions, Research Triangle Park, NC, 3Janssen Research & Development, LLC, Titusville, NJ, 4The University of California, San Francisco (UCSF, CA, USA Purpose: To quantify clinical trial participants’ and investigators’ judgments with respect to the relative importance of efficacy and safety attributes of antipsychotic treatments for schizophrenia, and to assess the impact of formulation and adherence.Methods: Discrete-choice experiment surveys were completed by patients with schizophrenia and physician investigators participating in two phase-3 clinical trials of paliperidone palmitate 3-month long-acting injectable (LAI antipsychotic. Respondents were asked to choose between hypothetical antipsychotic profiles defined by efficacy, safety, and mode of administration. Data were analyzed using random-parameters logit and probit models.Results: Patients (N=214 and physicians (N=438 preferred complete improvement in positive symptoms (severe to none as the most important attribute, compared with improvement in any other attribute studied. Both respondents preferred 3-month and 1-month injectables to oral formulation (P<0.05, irrespective of prior adherence to oral antipsychotic treatment, with physicians showing greater preference for a 3-month over a 1-month LAI for nonadherent patients. Physicians were willing to accept treatments with reduced efficacy for patients with prior poor adherence. The maximum decrease in efficacy (95% confidence interval [CI] that physicians would accept for switching a patient from daily oral to 3-month injectable was as follows: adherent: 9.8% (95% CI: 7.2–12.4, 20% nonadherent: 25.4% (95% CI: 21.0–29.9, and 50% nonadherent: >30%. For patients, adherent: 10.1% (95% CI: 6.1–14.1, nonadherent: the change in efficacy studied was

  5. Risperidone long-acting injectable monotherapy in the maintenance treatment of bipolar I disorder.

    Science.gov (United States)

    Quiroz, Jorge A; Yatham, Lakshmi N; Palumbo, Joseph M; Karcher, Keith; Kushner, Stuart; Kusumakar, Vivek

    2010-07-15

    Treatment adherence is a significant problem in patients with bipolar disorder. This study was designed to determine the efficacy of risperidone long-acting injectable (LAI) in the maintenance treatment of bipolar I disorder. Eligible patients with current or recent manic or mixed episodes (n = 559, aged 18-65 years) were treated with open-label oral risperidone for 3 weeks (period II) and open-label risperidone LAI for 26 weeks (n = 501; period III). Patients who maintained response (n = 303) were randomly allocated 1:1 to placebo injections (n = 149) or to continue risperidone LAI (n = 154) for up to 24 months (period IV). Most (77%) patients on risperidone LAI received a dose of 25 mg every 2 weeks during period IV. Time to recurrence for any mood episode (primary outcome variable) was significantly longer in the risperidone LAI group versus placebo (p or = 7% (compared with the period's baseline) occurred in 15% of patients in period III; in 12% of patients on risperidone LAI and 3% of patients on placebo in period IV. Risperidone LAI monotherapy significantly delayed the time to recurrence of mood episodes, versus placebo, in this controlled, randomized study in patients with bipolar I disorder. Risperidone LAI was tolerable and no new safety concerns emerged compared with previous studies of risperidone LAI. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  6. Physician and patient benefit–risk preferences from two randomized long-acting injectable antipsychotic trials

    Science.gov (United States)

    Katz, Eva G; Hauber, Brett; Gopal, Srihari; Fairchild, Angie; Pugh, Amy; Weinstein, Rachel B; Levitan, Bennett S

    2016-01-01

    Purpose To quantify clinical trial participants’ and investigators’ judgments with respect to the relative importance of efficacy and safety attributes of antipsychotic treatments for schizophrenia, and to assess the impact of formulation and adherence. Methods Discrete-choice experiment surveys were completed by patients with schizophrenia and physician investigators participating in two phase-3 clinical trials of paliperidone palmitate 3-month long-acting injectable (LAI) antipsychotic. Respondents were asked to choose between hypothetical antipsychotic profiles defined by efficacy, safety, and mode of administration. Data were analyzed using random-parameters logit and probit models. Results Patients (N=214) and physicians (N=438) preferred complete improvement in positive symptoms (severe to none) as the most important attribute, compared with improvement in any other attribute studied. Both respondents preferred 3-month and 1-month injectables to oral formulation (P30%. For patients, adherent: 10.1% (95% CI: 6.1–14.1), nonadherent: the change in efficacy studied was regarded as unimportant. Conclusion Improvement in positive symptoms was the most important attribute. Patients and physicians preferred LAIs over oral antipsychotics, with physicians showing a greater preference for 3-month over 1-month LAI. Physicians and patients were willing to accept reduced efficacy in exchange for switching a patient from an oral formulation to a LAI.

  7. Pharmacokinetics of an injectable long-acting formulation of doxycycline hyclate in dogs

    Directory of Open Access Journals (Sweden)

    Gutiérrez Lilia

    2012-06-01

    Full Text Available Abstract Based on its PK/PD ratios, doxycycline hyclate (DOX-h, a time-dependant antibacterial, is ideally expected to achieve both sustained plasma drug concentrations at or slightly above the MIC level for as long as possible between dosing intervals. Pursuing this end, a poloxamer-based matrix was used to produce a long-acting injectable preparation (DOX-h-LA and its serum concentrations vs. time profile investigated after its SC injection to dogs (≤ 0.3 mL per injection site, and results compared with the oral (PO and IV pharmacokinetics of DOX-h, prepared as tablet or as freshly made solution. A crossover (4 x 4 x 4 study design was employed with 12 Mongrel dogs, with washout periods of 21 days, and at dose of 10 mg/kg in all cases. DOX-h-LA showed the greatest values for bioavailability (199.48%; maximum serum concentration (Cmax value was 2.8 ± 0.3 with a time to reach Cmax (Tmax of 2.11 ± 0.12 h and an elimination half-life of 133.61 ± 6.32 h. Considering minimum effective serum concentration of 0.5 μg/mL, a dose-interval of at least 1 week h can be achieved for DOX-h-LA, and only 48 h and 24 h after the IV or PO administration of DOX-h as a solution or as tablets, respectively. A non-painful small bulge, apparently non-inflammatory could be distinguished at injection sites. These lumps dissipated completely in 30 days in all cases.

  8. Combination treatment with risperidone long-acting injection and psychoeducational approaches for preventing relapse in schizophrenia

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2013-10-01

    Full Text Available Yueren Zhao,1–3 Taro Kishi,1 Nakao Iwata,1 Manabu Ikeda3,4 1Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; 2Department of Psychiatry, Okehazama Hospital Fujita Kokoro Care Center, Toyoake, Aichi, Japan; 3Department of Neuropsychiatry, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan; 4Department of Neuropsychiatry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan Abstract: A recent meta-analysis showed that long-acting injectable (LAI antipsychotics were not superior to oral antipsychotics for preventing relapse in patients with schizophrenia. We therefore designed a treatment strategy combining risperidone LAI and COMPASS (COMprehensive Psycho-educational Approach and Scheme Set, an original psychoeducational program supporting treatment with risperidone LAI and evaluating subjective treatment satisfaction, transition of symptoms, and effectiveness in preventing symptomatic relapse. The aim of this study was to examine whether addition of COMPASS to risperidone LAI was more effective in preventing relapse in schizophrenia patients than risperidone LAI alone, with the latter group consisting of patients enrolled in a Phase III trial of risperidone LAI in Japan. Patients were followed up for 6 months, with COMPASS continuously implemented from the transition to the observation phase. The primary efficacy measurements were relapse rate (rates of rehospitalization and discontinuation due to inefficacy. Secondary efficacy measurements were the Brief Psychiatric Rating Scale (BPRS and Global Assessment of Functioning (GAF scores. Of the 96 patients originally enrolled, 19 (19.8% were discontinued from all causes. During the 6-month study period, ten of the 96 patients (10.4% relapsed, compared with a 12.2% relapse rate in patients enrolled in a Phase III trial of risperidone LAI in Japan. Patients showed significant improvements in BPRS total

  9. [A history of antipsychotic long-acting injections in the treatment of schizophrenia].

    Science.gov (United States)

    Crocq, M-A

    2015-02-01

    From a historical perspective, this article describes the use of antipsychotic long-acting injections (LAI) in the treatment of schizophrenia, a disorder that was defined in the final years of the 19th century. An efficient treatment for schizophrenia was discovered only in 1952 with the introduction of chlorpromazine, a phenothiazine derivative. Fairly soon, antipsychotics became available as LAI. The first compounds were fluphenazine enanthate (1966) and decanoate (1968) whose development is attributed to G.R. Daniel, a medical director at Squibb & Sons. Other first-generation antipsychotics long-acting injections (FGA-LAIs) were introduced in a rapid succession in the 1960s and 1970s. FGA-LAIs made a key contribution to the development of community psychiatry. As neuroleptics emptied psychiatric hospitals, it was important to ensure that patients could be taken care of in outpatient facilities. FGA-LAIs prevented covert non-compliance. Compliance was further reinforced by the social and psychological support of patients. The introduction of second-generation antipsychotics (SGA) led to a loss of interest in FGA-LAIs. This is evidenced by a drop in the number of papers published on this topic. The interest in LAI was revived with the introduction of the first SGA-LAI in 2003. Four different preparations have been approved in the decade between 2003 and 2013. SGA-LAIs differ from FGA-LAIs in the technology that is used to produce the depot effect, and also in the treatment objectives. The rationale for using SGA-LAIs is not only to prevent relapses due to treatment interruption, but also to achieve more constant plasma levels in order to reduce side effects due to excessive plasma levels and loss of efficacy due to insufficient plasma levels. Also, treatment objectives are no longer limited to controlling acute symptoms. Treatment objectives now include the alleviation of negative symptoms and cognitive deficits that are key prognostic factors. Copyright © 2014

  10. Pharmacokinetics of an injectable long-acting parenteral formulation of doxycycline hyclate in pigs.

    Science.gov (United States)

    Gutiérrez, L; Ocampo, L; Espinosa, F; Sumano, H

    2014-02-01

    Based on its ideal PK/PD ratios, doxycycline hyclate (DOX-h), a time-dependant antibacterial, is ideally expected to achieve sustained plasma drug concentrations at or slightly above the MIC level for as long as possible between dosing intervals. Pursuing this end, a poloxamer-based matrix was used to produce a 10% long-acting injectable preparation (DOX-h-LA) and its serum concentrations vs. time profile investigated after its injection to pigs in the pericaudal s.c. by parallel design. Results were compared with the forced oral bolus dose and i.v. pharmacokinetics of DOX-h. For this study, 12 recently weaned pigs per group were included in this trial, and a dose of 20 mg/kg was injected in all cases. DOX-h-LA showed the greatest values for bioavailability (115.38%); maximum serum concentration (Cmax) value was 1.5 ± 0.2 with a time to reach Cmax of 3.41 ± 0.04 h and an elimination rate constant of 70.93 ± 0.87( ) h. Considering minimum effective serum concentration of 0.5 μg/mL, a dose interval of at least 5 days can be achieved for DOX-h-LA, whereas p.o. and i.v. dosing of DOX-h may only last 11 and 15 h, respectively. Pigs were slaughtered on day 30 after this trial, and no visible remnants of the preparation were detected neither fibrosis was observed after a thorough macroscopic and histopathological analysis.

  11. Clinical Decision-Making in the Treatment of Schizophrenia: Focus on Long-Acting Injectable Antipsychotics.

    Science.gov (United States)

    Samalin, Ludovic; Garnier, Marion; Auclair, Candy; Llorca, Pierre-Michel

    2016-11-19

    The purpose of this study was to identify clinician characteristics associated with higher prescription rates of long-acting injectable (LAI) antipsychotics, as well as the sources that influence medical decision-making regarding the treatment of schizophrenia. We surveyed 202 psychiatrists during six regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, and Strasbourg). Data on the characteristics of practice, prescription rates of antipsychotic, and information sources about their clinical decisions were collected. Most psychiatrists used second-generation antipsychotics (SGAs), and preferentially an oral formulation, in the treatment of schizophrenia. LAI SGAs were prescribed to 30.4% of schizophrenic patients. The duration and type of practice did not influence the class or formulation of antipsychotics used. The clinicians following the higher percentage of schizophrenic patients were associated with a higher use of LAI antipsychotics and a lower use of oral SGAs. Personal experience, government regulatory approval, and guidelines for the treatment of schizophrenia were the three main contributing factors guiding clinicians' decision-making regarding the treatment of schizophrenia. The more clinicians follow schizophrenic patients, the more they use LAI antipsychotics. The development of specialized programs with top specialists should lead to better use of LAI antipsychotics in the treatment of schizophrenia.

  12. Clinical Decision-Making in the Treatment of Schizophrenia: Focus on Long-Acting Injectable Antipsychotics

    Directory of Open Access Journals (Sweden)

    Ludovic Samalin

    2016-11-01

    Full Text Available The purpose of this study was to identify clinician characteristics associated with higher prescription rates of long-acting injectable (LAI antipsychotics, as well as the sources that influence medical decision-making regarding the treatment of schizophrenia. We surveyed 202 psychiatrists during six regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, and Strasbourg. Data on the characteristics of practice, prescription rates of antipsychotic, and information sources about their clinical decisions were collected. Most psychiatrists used second-generation antipsychotics (SGAs, and preferentially an oral formulation, in the treatment of schizophrenia. LAI SGAs were prescribed to 30.4% of schizophrenic patients. The duration and type of practice did not influence the class or formulation of antipsychotics used. The clinicians following the higher percentage of schizophrenic patients were associated with a higher use of LAI antipsychotics and a lower use of oral SGAs. Personal experience, government regulatory approval, and guidelines for the treatment of schizophrenia were the three main contributing factors guiding clinicians’ decision-making regarding the treatment of schizophrenia. The more clinicians follow schizophrenic patients, the more they use LAI antipsychotics. The development of specialized programs with top specialists should lead to better use of LAI antipsychotics in the treatment of schizophrenia.

  13. Long Acting Single Injection Caudal Anesthesia—1,208 Obstetrical Deliveries with Mepivacaine

    Science.gov (United States)

    Gunther, Ronald E.; Harer, W. Benson

    1966-01-01

    Long acting, single injection caudal anesthesia with mepivacaine was studied in 1,208 obstetrical cases. A 1 per cent solution was used in 671 patients and compared with a 1.5 per cent concentration in 537. No remarkable differences were found between the two groups. The 1 per cent solution provided relief of labor discomfort for from 60 to 180 minutes with an average of 110 minutes. In contrast, the 1.5 per cent solution provided an average of 115 minutes with a range of 80 to 210 minutes. A total volume of 30 ml of anesthetic agent yielded anesthesia to a level of the tenth thoracic vertebra or higher in 91 per cent of patients. Significant alterations in blood pressure were uncommon. About 1 per cent of patients required a vasopressor because of a drop in systolic blood pressure below 80 mm of mercury. Another 8 per cent had a drop of over 20 points in systolic pressure but from high enough levels that they did not require a vasopressor. Toxic effects similar to those of lidocaine were found in slightly more than 1 per cent of cases. This anesthesia requires a higher incidence of operative intervention for delivery. PMID:5980717

  14. Effectiveness, Adverse Effects and Drug Compliance of Long-Acting Injectable Risperidone in Children and Adolescents.

    Science.gov (United States)

    Ceylan, Mehmet Fatih; Erdogan, Betül; Tural Hesapcioglu, Selma; Cop, Esra

    2017-07-19

    Although the use of oral risperidone in children and adolescents has been well studied, there is little information on the intramuscular use of long-acting injectable risperidone (LAIR). The aims of this study were to investigate the effectiveness and adverse effects of LAIR in children and adolescents with conduct disorder, bipolar disorder, and schizophrenia. In total, 42 patients (age range 12-17 years) who were non-adherent to oral antipsychotic drugs, received 25 mg/day of LAIR intramuscularly every 2 weeks. The drug was administered at least four times and up to 66 times (median drug use: 9.50 times). The effectiveness and adverse effects of the treatment were examined. There was an improvement in 13 (92.8%) of the 14 patients diagnosed with bipolar disorder, in 25 (78.1%) of 32 patients diagnosed with conduct disorder and in one (50%) of two patients diagnosed with schizophrenia. Six patients had comorbid conduct disorder and bipolar disorder. Totally, 81% of the patients improved with LAIR. Weight-gain, daytime somnolence, muscle stiffness and spasms, impaired concentration, and fatigue were the most common side effects through the whole sample. Menstrual problems were common in girls. In the study, 57.1% of the patients continued to receive their injections regularly until the end of the treatment, under physician control. A total of 16.7% discontinued the treatment due to non-adherence. The LAIR treatment was terminated in 26.2% of the patients, due to weight-gain, dystonia, and galactorrhea. In children and adolescents with conduct disorder, bipolar disorder and schizophrenia who show noncompliance with oral drugs, LAIR may improve treatment compliance. LAIR is a reliable treatment in terms of its effectiveness. Weight-gain, dystonia, and galactorrhea were the adverse effects that were responsible for LAIR treatment cessation.

  15. Combination treatment with risperidone long-acting injection and psychoeducational approaches for preventing relapse in schizophrenia

    Science.gov (United States)

    Zhao, Yueren; Kishi, Taro; Iwata, Nakao; Ikeda, Manabu

    2013-01-01

    A recent meta-analysis showed that long-acting injectable (LAI) antipsychotics were not superior to oral antipsychotics for preventing relapse in patients with schizophrenia. We therefore designed a treatment strategy combining risperidone LAI and COMPASS (COMprehensive Psycho-educational Approach and Scheme Set), an original psychoeducational program supporting treatment with risperidone LAI and evaluating subjective treatment satisfaction, transition of symptoms, and effectiveness in preventing symptomatic relapse. The aim of this study was to examine whether addition of COMPASS to risperidone LAI was more effective in preventing relapse in schizophrenia patients than risperidone LAI alone, with the latter group consisting of patients enrolled in a Phase III trial of risperidone LAI in Japan. Patients were followed up for 6 months, with COMPASS continuously implemented from the transition to the observation phase. The primary efficacy measurements were relapse rate (rates of rehospitalization and discontinuation due to inefficacy). Secondary efficacy measurements were the Brief Psychiatric Rating Scale (BPRS) and Global Assessment of Functioning (GAF) scores. Of the 96 patients originally enrolled, 19 (19.8%) were discontinued from all causes. During the 6-month study period, ten of the 96 patients (10.4%) relapsed, compared with a 12.2% relapse rate in patients enrolled in a Phase III trial of risperidone LAI in Japan. Patients showed significant improvements in BPRS total scores (P = 0.0031), BPRS positive (P = 0.0451), BRPS negative (P < 0.0001), and general subscale scores (P = 0.0031), and GAF (P < 0.0001) from baseline to 6 months. In conclusion, the lower relapse rate observed in patients treated with COMPASS plus risperidone LAI than in patients treated with risperidone LAI alone suggests that COMPASS may have benefits in the treatment of schizophrenia, indicating a need for randomized, controlled trials in larger numbers of patients. PMID:24194642

  16. Modeling the budget impact of long-acting injectable paliperidone palmitate in the treatment of schizophrenia in Japan

    Directory of Open Access Journals (Sweden)

    Mahlich J

    2015-05-01

    Full Text Available Jörg Mahlich,1,2 Masamichi Nishi,3 Yoshimichi Saito11Health Economics, Janssen Pharmaceutical KK, Tokyo, Japan; 2Düsseldorf Institute for Competition Economics, University of Düsseldorf, Düsseldorf, Germany; 3Pricing, Janssen Pharmaceutical KK, Tokyo, JapanBackground: The cost of schizophrenia in Japan is high and new long-acting injectable (LAI antipsychotics might be able to reduce costs by causing a reduction of hospital stays. We aim to estimate budget effects of the introduction of a new 1-month LAI, paliperidone palmitate, in Japan.Methods: A budget impact analysis was conducted from a payer perspective. The model took direct costs of illness into account (ie, costs for inpatient and outpatient services, as well as drug costs. The robustness of the model was checked using a sensitivity analysis.Results: According to our calculations, direct total costs of schizophrenia reach 710,500 million yen a year (US$6 billion. These costs decrease to 691,000 million yen (US$5.9 billion 3 years after the introduction of paliperidone palmitate.Conclusion: From a payer point of view, the introduction of a new treatment for schizophrenia in Japan helps to save resources and is not associated with a higher financial burden.Keywords: budget impact, schizophrenia, long-acting injectables, paliperidone, Japan

  17. Impact of long-acting injectable antipsychotics on medication adherence and clinical, functional, and economic outcomes of schizophrenia

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    Kaplan G

    2013-11-01

    Full Text Available Gabriel Kaplan,1,2 Julio Casoy,3 Jacqueline Zummo3 1Behavioral Health Services, Bergen Regional Medical Center, Paramus, NJ, USA; 2Department of Psychiatry, Rutgers New Jersey Medical School, Newark, NJ, USA; 3Medical Affairs, Alkermes, Inc., Waltham, MA, USA Abstract: Schizophrenia is a debilitating chronic disease that requires lifelong medical care and supervision. Even with treatment, the majority of patients relapse within 5 years, and suicide may occur in up to 10% of patients. Poor adherence to oral antipsychotics is the most common cause of relapse. The discontinuation rate for oral antipsychotics in schizophrenia ranges from 26% to 44%, and as many as two-thirds of patients are at least partially nonadherent, resulting in increased risk of hospitalization. A very helpful approach to improve adherence in schizophrenia is the use of long-acting injectable (LAI antipsychotics, although only a minority of patients receive these. Reasons for underutilization may include negative attitudes, perceptions, and beliefs of both patients and health care professionals. Research shows, however, significant improvements in adherence with LAIs compared with oral drugs, and this is accompanied by lower rates of discontinuation, relapse, and hospitalization. In addition, LAIs are associated with better functioning, quality of life, and patient satisfaction. A need exists to encourage broader LAI use, especially among patients with a history of nonadherence with oral antipsychotics. This paper reviews the impact of nonadherence with antipsychotic drug therapy overall, as well as specific outcomes of the schizophrenia patient, and highlights the potential benefits of LAIs. Keywords: adherence, long-acting injectable, antipsychotics, schizophrenia, discontinuation, relapse

  18. A Muhicentered Clinical Trial of the Long-acting Injectable Contraceptive Depo Provera in Chinese Women

    Institute of Scientific and Technical Information of China (English)

    SunDan-li; ShaoQing-xiang; SangGuo-wei

    2005-01-01

    This study was an open trial where 1994 subjects each received Depo Provera injectable contraceptive every three months for one year and were observed a total of 20,294.3 woman months.At the time of observation,only one accidental pregnancy had occurred giving a use-effectiveness rate of 99.94% and a cumulative continuation rate of 72.8%.There were no significant adverse effects on weight and bolld pressure.The main side effects were spotting,prolonged bleeding,and amenorrhea and these were alsothe main reasons of discontinuation.Complaints related to bleeding problems gradually decreased and complaints of amenorrhea increased with continued use. In lactating women,side effects occurrence rate was lower and continuation rate was higher in comparison with non-lactating women.Users did not report any effect on milk secretion.The results of this study confirm that Depo Provera is a very effective contraceptive method.With appropriate counseling and medical support,high acceptability and continuation rate can be achieved. Depo Provera is especially suitable for lactating women and could become a popular contraceptive method for lactating Chinese women.

  19. Worsening of myasthenia gravis after administration of injectable long-acting risperidone for treatment of schizophrenia; first case report and a call for caution.

    Science.gov (United States)

    Al-Hashel, Jasem Y; Ismail, Ismail Ibrahim; John, John K; Ibrahim, Mohammed; Ali, Mahmoud

    2016-01-01

    Myasthenia gravis is an autoimmune disease characterized by muscle weakness due to autoantibodies affecting the neuromuscular junction. Co-occurrence of myasthenia gravis and schizophrenia is very rare and raises a challenge in management of both diseases. Antipsychotic drugs exhibit anticholinergic side effects and have the potentials of worsening myasthenia. Long-acting risperidone is an injectable atypical antipsychotic drug that has not been previously reported to worsen myasthenia gravis in literature. We report the first case report of worsening of myasthenia after receiving long-acting risperidone injection for schizophrenia in a 29-year-old female with both diseases. She started to have worsening 2 weeks following the first injection and her symptoms persisted despite receiving plasma exchange. This could be explained by the pharmacokinetics of the drug. We recommend that long-acting risperidone should be used with caution in patients with myasthenia gravis, and clinicians must be aware of the potential risks of this therapy.

  20. Olanzapine Injection

    Science.gov (United States)

    ... of bed slowly, resting your feet on the floor for a few minutes before standing up.you should know that you may experience hyperglycemia (increases in your blood sugar) while you are taking this medication, even ...

  1. Effectiveness of injectable risperidone long-acting therapy for schizophrenia: data from the US, Spain, Australia, and Belgium

    Directory of Open Access Journals (Sweden)

    Macfadden Wayne

    2011-04-01

    Full Text Available Abstract Background Because wide variations in mental health care utilization exist throughout the world, determining long-term effectiveness of psychotropic medications in a real-world setting would be beneficial to physicians and patients. The purpose of this analysis was to describe the effectiveness of injectable risperidone long-acting therapy (RLAT for schizophrenia across countries. Methods This was a pragmatic analysis of data from two prospective observational studies conducted in the US (Schizophrenia Outcomes Utilization Relapse and Clinical Evaluation [SOURCE]; ClinicalTrials.gov registration number for the SOURCE study: NCT00246194 and Spain, Australia, and Belgium (electronic Schizophrenia Treatment Adherence Registry [eSTAR]. Two separate analyses were performed to assess clinical improvement during the study and estimate psychiatric hospitalization rates before and after RLAT initiation. Clinical improvement was evaluated using the Clinical Global Impressions-Severity (CGI-S and Global Assessment of Functioning (GAF scales, and change from baseline was evaluated using paired t tests. Psychiatric hospitalization rates were analyzed using incidence densities, and the bootstrap resampling method was used to examine differences between the pre-baseline and post-baseline periods. Results The initial sample comprised 3,069 patients (US, n = 532; Spain, n = 1,345; Australia, n = 784; and Belgium, n = 408. In all, 24 months of study participation, completed by 39.3% (n = 209, 62.7% (n = 843, 45.8% (n = 359, and 64.2% (n = 262 of patients from the US, Spain, Australia, and Belgium, respectively, were included in the clinical analysis. Improvements compared with baseline were observed on both clinical assessments across countries (P P P Conclusions RLAT in patients with schizophrenia was associated with improvements in clinical and functional outcomes and decreased hospitalization rates in the US, Spain, Australia, and Belgium, despite

  2. Long-term outcomes in patients with schizophrenia treated with risperidone long-acting injection or oral antipsychotics in Spain: results from the electronic Schizophrenia Treatment Adherence Registry (e-STAR).

    Science.gov (United States)

    Olivares, J M; Rodriguez-Morales, A; Diels, J; Povey, M; Jacobs, A; Zhao, Z; Lam, A; Villalobos Vega, J C; Cuéllar, J Alonso; de Castro, F J Alberca; Quintero, C Morillo-Velarde; Martíin, J F Román; Domínguez, P Tabares; Ojeda, J L Prados; Cortés, S Sanz; Cala, F I Mata; Marín, C Gutiérrez; Castro, L Moyano; Duaso, M A Haza; Albarracín, J Requena; Vergara, G Narbona; Benítez, A Fernández; Cleries, F Mayoral; Pérez-Brian, J M García-Herrera; Aragón, A Bordallo; Navarro, J C Rodríguez; Biedma, J A Algarra; de Pedro, R Bravo; González, J F Delgado; López, M E Jaén; Moreno, H Díaz; López, J A Soto; Rodríguez, E Ojeda; de Hoyos, C Martínez; Sacristán, M Pardilla; Martín, M D Molina; Ballesteros, E Martín; Rodríguez, P A Sopelana; Menéndez, L Fernández; Rivas, R Santos; del Pino Cuadrado, P; Lauffer, J Correas; Solano, J J Rodríguez; Martínez, J M Fernández; Solano, F García; Rodríguez, P García-Lamberde; Rodríguez, J A Romero; Cano, T Rodríguez; Fortacin, M Ducaju; Lobeiras, J M Blanco; Sampedro, J M Piñeiro; Bravo, A Pérez; Pellicer, A Fernández; López, M D Alonso; Liste, J Fraga; Fernández, M Riobo; Losada, A Casas; Mendez, R Vazquez-Noguerol; Romero, S Agra; Blanco, J J Blanco; Bonaselt, I Tortajada; Mahia, M C García; del Valle, E Ferrer Gómez; Yañez, P Quiroga; Camarasa, M Gelabert; Alonso, J A Barbado; Mendez, G Florez; Feliz, F Doce; Lamela, M A López; Piñero, M Vega; Alvarado, P Fuentes; Gómez, I López; Martín, P Fadon; Gómez, J L Santos; López, A García; Jiménez, A Rodríguez; Nafs, A Escudero; Barquero, N Casas; Ortiz, R Fernández-Villamor; Noguera, J L Velez; Carrasco, P Ruiz; Muñoz, J Martín; Palma, M Masegoza; Hortelano, C Marín; Bonome, L Sánchez; Sevilla, J Sánchez; Juan, J M Mongil San; Ramos, J M García; Muñoz, J L Vallejo; Guisasola, J Elorza; Vazquez, L Santamaria; Guerras, F Campo; Nebot, F J Arrufat; Fernández, F J Baron; Nicolau, A L Palomo; Subirats, R Catala; Kidias, M Messays; Navarro, V Fabregat; García, B Frades; del Rosal, F Mejias; de Vicente Muñoz, T; Ballester, J Año; Lieb, P Malabia; Martel, A Delgado; Bea, E Roca; Joaquim, I Grau; Enjuanes, F Boatas; Piñol, M Bañuelos; Carbonell, E Fontova I; Muñoz, R Martín; Giribets, C Argila; Sans, L Albages; Blanco, A Serrano; Felipe, M Arcega; Muñoz, P González; Villanueva, A Pons; Arroyo, M Bernardo; Borri, R Coronas; Fallada, S Miret; Merola, M Celma; Rodon, E Parellada; Palmes, J R Pigem; Martínez, E Pérez; Catala, J Matarredona; Coca, A Sandoval; Ferrandiz, F Pascual; Paya, E Ferrandiz; Caballero, G Iturri; Bonet, A Franco; Figueras, J Fluvia; Pagador, P Moreno; Garibo, M Medina; Camo, V Pérez; Carrillo, C Sanz; Valero, C Pelegrin; Rebollo, F J Caro; García Campayo, J; Sala Ayma, J M Sala; Roig, M Martínez; de Uña Mateos, M A; Bertolin, R García; García, A Martín; Mazo, F Jiménez; Velasco, J L Galvez; Pérez, L Santa Maria; Casado, C Jiménez; Barba, J J Mancheño; Diaz, M Conde; Rubio, J P Alcon; Mandoli, A Soler; Herrero, A Uson; Martínez, A Rodríguez; Serrano, P Salgado; Rodríguez, E Nieto; Montesinos, J Segui; Macia, J Ferragud; Mateos Marcos, A Mateos; Soto, J V Pérez-Fuster; Dumont, M Verdaguer; Pagan, J Parra; Martínez, V Balanza; Santiuste de Pablos, M; Delgado, C Espinosa; Quiles, M D Martínez; López, F J Manzanera; Navarro, P Pozo; Torres, A Micol; Ingles, F J Martínez; Arias-Camison, J M Salmeron; Manzano, J C López; Peña, R Villanueva; Guitarte, G Petersen; Fontecilla, H Blasco; Romero, J Barjau; Gil, R Sanz; Lozano, J Marín; Adanez, L Donaire; Zarranz Herrera-Oria, I; Jiménez, J Pérez; Vaz, F Carrato; García, O Sanz; Anton, C Contreras; Casula, R Reixach; Hernandez, M C Natividad; Escabias, F Teba; Torresano, J Rodríguez; Pérez-Villamil, A Huidobro; Estevez, L; Figuero, M Aragües; Muñoz de Morales, A; Calvin, J L Rodríguez; Criado, M Delgado; Rodríguez, V Molina; Ambrosolio, E Balbo; Madera, P M Holgado; Alfaro, G Ponce; Vidal, M M Rojas; Valtuille, A García; Ruiz, O; Cabornero, G Lucas; Echevarria Martínez de Bujo, M; Mallen, M J Maicas; Puigros, J Santandreu; Martorell, A Liñana; Forteza, A Clar; Arrebola, E Rodríguez; Rodríguez de la Torre, M; Saiz, C G Anton; Bardolet I Casas, C; Linde, E Rodríguez; De Arce Cordon, R; Molina, E M Padial; Carazo, F J Ruiz; Romero, J J Muro; Cano, D Vico; Dorado, M Soria; Velazquez, S Campos; Sánchez, A J Rodríguez; Leon, S Ocio; Sánchez, K Pachas; Benitez, M Henry; Zugarramurai, A Intxausti; Contreras, M A; De la Varga González, M; Marín, P Barreiro; Robina, F Gómez; García, M Sánchez; Pérez, F J Otero; Bros, P Cubero; Gómez, A Carrillo; de Dios Molina Martín, J; Perera, J L Carrasco; Averbach, M C; Perera, J L Carrasco; Palancares, E Goenaga; Gallego de Dios, M T; Rojo, C Fernández; Iglesias, S Sánchez; Merino, M I Rubio; Mestre, N Prieto; Urdaniz, A Pérez; Sánchez, J M Martínez; Seco, R Gordo; Muñoz, J Franco; Agut, M Mateos; Lozano, M L Blanco; Herguedas, F Martín; Pena, A Torcal; García, J Vicente; Martínez, A Varona; Sanz Granado, O Sanz; Fernández, M A Medina; Canseco, J M Moran; López, P A Megia; Martín, M A Franco; Barrio, J A Espina; Ubago, J Giner; Bennassar, M Roca; Díez, J M Olivares; Fleta, J L Hernandez; Fortes, F Porras; López, C Arango; Medina, O; Alvarez, D Figuera; Roca, J M Peña; Valladolid, G Rubio; Tavera, J A Furquet; García-Castrillon Sales, J A; Llordes, I Batalla; Melgarejo, C Anchuistegui; Cañas de la Paz, F; Callol, V Vallés; García, M Bousoño; García, J Bobes; Leal, F J Vaz; Corrales, E Cáceres; Iglesias, E Sánchez; Gómez, M A Carreiras; Serrano, G García; Chillarón, E G Román; Aguado, F J Samino; Castillo, J J Molina; González, A González; Vázquez, J Gallardo; Peralvarez, M Bolivar; Diaz, M Rios; Mesa, M Ybarzabal; Artiles, F J Acosta; Chao, M Ajoy; Mesa, M Ybarzabal; del Rosario Santana, P; Escudero, M A García; Berenguer, M Molla; Llacer, J M Bonete; Berna, J A Juan; Ortiz, J Barragán; Pardell, L Tost; Hernández-Alvarez de Sotomayor, C; Méndez, M R Cejas; Garate, R Cabrera; Múgica, B Díaz; González, M Caballero; Domingo, J Pujol; Navarro, C Sáez; Vera, G Selva; Cuquerella, M A; Monzo, J Lonjedo; Boada, P Cervera; Pérez, M F Martín; Parrado, E Carrasco; Sánchez, J J Yañez; Fernández, J Calvo

    2009-06-01

    The electronic Schizophrenia Treatment Adherence Registry (e-STAR) is a prospective, observational study of patients with schizophrenia designed to evaluate long-term treatment outcomes in routine clinical practice. Parameters were assessed at baseline and at 3 month intervals for 2 years in patients initiated on risperidone long-acting injection (RLAI) (n=1345) or a new oral antipsychotic (AP) (n=277; 35.7% and 36.5% on risperidone and olanzapine, respectively) in Spain. Hospitalization prior to therapy was assessed by a retrospective chart review. At 24 months, treatment retention (81.8% for RLAI versus 63.4% for oral APs, p<0.0001) and reduction in Clinical Global Impression Severity scores (-1.14 for RLAI versus -0.94 for APs, p=0.0165) were significantly higher with RLAI. Compared to the pre-switch period, RLAI patients had greater reductions in the number (reduction of 0.37 stays per patient versus 0.2, p<0.05) and days (18.74 versus 13.02, p<0.01) of hospitalizations at 24 months than oral AP patients. This 2 year, prospective, observational study showed that, compared to oral antipsychotics, RLAI was associated with better treatment retention, greater improvement in clinical symptoms and functioning, and greater reduction in hospital stays and days in hospital in patients with schizophrenia. Improved treatment adherence, increased efficacy and reduced hospitalization with RLAI offer the opportunity of substantial therapeutic improvement in schizophrenia.

  3. Treatment and control of bovine sarcoptic and psoroptic mange infestation with ivermectin long-acting injectable (IVOMEC(®) GOLD).

    Science.gov (United States)

    Hamel, Dietmar; Joachim, Anja; Löwenstein, Michael; Pfister, Kurt; Silaghi, Cornelia; Visser, Martin; Winter, Renate; Yoon, Stephen; Cramer, Luiz; Rehbein, Steffen

    2015-02-01

    The efficacy of ivermectin long-acting injection (IVM LAI, IVOMEC® GOLD, Merial; 3.15 % ivermectin w/v) formulation was evaluated in cattle with induced Sarcoptes scabiei var. bovis or Psoroptes ovis infestations. A total of 64 cattle were included in this series of four studies, with 16 animals per study. Approximately, 8 weeks following initial induced mite infestation, cattle were allocated to treatment groups based on decreasing pre-treatment bodyweights. Treatments (saline (control) or IVM LAI (630 mcg ivermectin/kg bodyweight) at 1 mL/50 kg bodyweight) were administered by a single subcutaneous injection in front of the right shoulder on Day 0. Skin scrapings were collected prior to treatment and at approximately weekly intervals for 8 weeks thereafter to establish live mite counts. Character and extent of skin lesions were evaluated at each sampling. Animals were weighed before treatment and at the end of the studies. Mite counts of the IVM LAI-treated animals were significantly (p studies at all occasions post-treatment. In the two Sarcoptes studies, IVM LAI-treated cattle were free of mites at 14 days after treatment and in the Psoroptes studies at 13 or 28 days post-treatment. All IVM LAI-treated cattle remained free of mites to the end of the studies while all control animals remained infested. Mange lesions of the IVM LAI-treated animals improved significantly (p studies) and from Days 28 or 34 (Psoroptes studies). In all studies, mean weight gain over the 8 week post-treatment period was significantly (p studies, 64.1 and 68.6 kg vs. 46.9 and 48.6 kg, respectively; Psoroptes studies, 43.0 and 43.4 kg vs. 20.8 and 34.9 kg, respectively. All animals accepted the treatment well, and no treatment-related health problems and adverse events were observed throughout the studies. These studies demonstrated the high efficacy of IVOMEC® GOLD against sarcoptic and psoroptic mange in cattle.

  4. Role of Long-Acting Injectable Second-Generation Antipsychotics in the Treatment of First-Episode Schizophrenia: A Clinical Perspective

    Directory of Open Access Journals (Sweden)

    Radovan Přikryl

    2012-01-01

    Full Text Available Approximately 80% of patients with the first-episode schizophrenia reach symptomatic remission after antipsychotic therapy. However, within two years most of them relapse, mainly due to low levels of insight into the illness and nonadherence to their oral medication. Therefore, although the formal data available is limited, many experts recommend prescribing long-acting injectable second-generation antipsychotics (mostly risperidone or alternatively paliperidone in the early stages of schizophrenia, particularly in patients who have benefited from the original oral molecule in the past and agree to receive long-term injectable treatment. Early application of long-acting injectable second-generation antipsychotics can significantly reduce the risk of relapse in the future and thus improve not only the social and working potential of patients with schizophrenia but also their quality of life.

  5. Maintenance therapy with once-monthly administration of long-acting injectable risperidone in patients with schizophrenia or schizoaffective disorder: a pilot study of an extended dosing interval

    Directory of Open Access Journals (Sweden)

    Naessens Ineke

    2007-01-01

    Full Text Available Abstract Background Several clinical studies have established the efficacy, safety, and tolerability of long-acting risperidone administered once every 2 weeks in patients with schizophrenia or schizoaffective disorder. This report evaluates preliminary efficacy, safety, tolerability, and pharmacokinetic data for a novel (once-monthly administration of long-acting injectable risperidone 50 mg in patients with schizophrenia or schizoaffective disorder. Methods Clinically stable patients participated in a 1-year, open-label, single-arm, multicenter pilot study. During the 4-week lead-in phase, patients received long-acting risperidone 50 mg injections every 2 weeks, with 2 weeks of oral risperidone supplementation. Injections of long-acting risperidone 50 mg every 4 weeks followed for up to 48 weeks, without oral supplementation. The primary endpoint was relapse; other assessments included PANSS, CGI-S, adverse event reports, and determination of risperidone and 9-hydroxyrisperidone plasma concentrations. Results Twelve patients in the intent-to-treat population (n = 67 met relapse criteria (17.9%. Relapse risk at 1 year was estimated as 22.4%. Non-statistically significant improvements in symptoms (PANSS and clinical status (CGI-S at endpoint were observed. The most common adverse events included schizophrenia aggravated not otherwise specified (19.5%, anxiety (16.1%, insomnia (16.1%, and headache (11.5%. There were no unexpected safety and tolerability findings. Mean plasma concentrations for risperidone and 9-hydroxyrisperidone were generally stable during the study. Conclusion Once-monthly dosing of long-acting risperidone was well tolerated, associated with a relatively low relapse rate (similar to that reported with other antipsychotics, and maintained the clinically stable baseline status of most patients. Although the results suggest that some symptomatically stable patients with schizophrenia or schizoaffective disorder might be safely

  6. Acute Metabolic Effects of Olanzapine Depend on Dose and Injection Site

    Directory of Open Access Journals (Sweden)

    Candice M. Klingerman

    2015-11-01

    Full Text Available Atypical antipsychotics (AAPs, such as olanzapine (OLZ, are associated with metabolic side effects, including hyperglycemia. Although a central mechanism of action for the acute effects on glycemia has been suggested, evidence for peripheral versus central effects of AAPs has been mixed and has not been explored for an effect of OLZ on the respiratory exchange ratio (RER. Here, we tested the hypothesis that some inconsistencies in the glycemic responses are likely a result of different doses and central sites of injection. We also compared the effects of central versus peripherally administered OLZ on the RER of unsedated rats. Third ventricle infusion of OLZ at 0.3 mg/kg caused hyperglycemia within 30 minutes, with a higher dose (1.8 mg/kg needed to elicit a similar response in the lateral ventricles. In contrast, 3 mg/kg of OLZ was needed to raise blood glucose within 30 minutes when given intragastrically, and 10 mg/kg resulted in a prolonged hyperglycemia lasting at least 60 minutes. Third ventricle injection of OLZ significantly decreased RER after 75 minutes, whereas intragastric OLZ resulted in a faster drop in RER after 30 minutes. Since changes in glycemia were most sensitive when OLZ was infused into the third ventricle, but effects on RER were more rapidly and efficaciously observed when the drug was given peripherally, these results raise the likelihood of a dual mechanism of action involving hypothalamic and peripheral mechanisms. Some discrepancies in the literature arising from central administration appear to result from the injection site and dose.

  7. 长效注射剂释药技术研究进展%Progress of drug delivery technologies for long-acting injections

    Institute of Scientific and Technical Information of China (English)

    张芳; 杨志强; 王杏林

    2013-01-01

    随着科学技术的不断发展,人们对药物治疗作用的要求越来越高.长效注射剂因可延长药物的作用时间、减少注射次数、改善患者的顺应性而成为当前药剂研究的一大热点.本文以释药技术为主线,综述了前体药物技术、PEG化技术、微球技术、难溶盐技术、注射植入剂、DepoFoam技术、温敏型原位凝胶等释药技术在长效注射剂中的应用.%With the constant development of science and technology, people's demand for drug therapy effect has become higher and higher. Due to the fact that long-acting injection can prolong the action time, reduce the frequency of administration and improve the patient compliance, it has become a hot area of pharmaceutie research. In this review, we introduced sustained-release drug delivery systems and reviewed the application of the technologies such as prodrug, PEGylation, microspheres, insoluble salts technology, injectable implants, Depo-Foam technology and temperature-sensitive in situ gel in the development of long-acting injections.

  8. Benefit of fluoroscopically guided intraarticular, long-acting corticosteroid injection for subtalar arthritis in juvenile idiopathic arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Cahill, Anne M.; Cho, Sandy S. [Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Baskin, Kevin M. [Children' s Hospital of Philadelphia, Department of Pediatrics, Division of Rheumatology, Philadelphia, PA (United States); Beukelman, Timothy; Cron, Randy Q. [Children' s Hospital of Pittsburgh, Department of Radiology, Pittsburgh, PA (United States); Kaye, Robin D. [Children' s Hospital of Wisconsin, Department of Radiology, Milwaukee, WI (United States); Towbin, Richard B.

    2007-06-15

    Children with arthritis may endure a lifetime of disfigurement, dysfunction, and pain if acute inflammation progresses to chronic changes in the joint cartilage and underlying bone. Intraarticular steroids have become an integral component of treatment, but at times are difficult to deliver to joints, such as the subtalar joint, that have complex anatomies. We describe our technique and outcomes using fluoroscopically guided intraarticular subtalar steroid injection in patients with active symptoms of juvenile idiopathic arthritis (JIA). Fluoroscopically guided subtalar joint injections were performed in 38 children (mean age 6.7 years). Medical records were reviewed retrospectively and improvement was evaluated clinically by the degree of foot movement in eversion and inversion. Subtalar joint injection was technically successful in 100% of the JIA patients with improvement in physical symptoms in 34/38 (89%). Of the 38 children, 32 were followed up within 13 weeks of the initial injection and, therefore, satisfied the eligibility criteria for resolution of arthritis. Of these 32 children, 14 showed clinical resolution (44%). The mean duration of improvement was 1.2 {+-} 0.9 years. Children with a longer interval (>1 year) from diagnosis to treatment had significantly less resolution (P = 0.04). Local subcutaneous atrophy or hypopigmentation were observed in 53% of the children after steroid injection (20/38). These minor complications were associated with a greater volume of steroid injected into the site per child (P = 0.02). Fluoroscopically guided subtalar joint injection is an effective treatment for subtalar arthropathy. Prompt referral for intraarticular steroid treatment in the acute phase improves response. Skin changes often occur at the injection site, and specific precautions should be employed to reduce this risk. Prospective study is indicated to determine the most effective treatment strategy to prevent long-term pain and disability. (orig.)

  9. Effect of long-acting progestagen-only injectable contraceptives on carbohydrate metabolism and its hormonal profile.

    Science.gov (United States)

    Fahmy, K; Abdel-Razik, M; Shaaraway, M; al-Kholy, G; Saad, S; Wagdi, A; al-Azzony, M

    1991-10-01

    Two groups, each composed of 20 women, who used depomedroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) injectable contraceptives were investigated for changes in 75-g OGTT and in the fasting and two-hour post oral glucose load (2-hours) levels of serum insulin, growth hormone, glucagon, cortisol and blood pyruvate. Samples were taken before and 3, 6 and 12 months after use of injectables. DMPA and NET-EN caused significant changes in mean blood glucose and pyruvate and in mean serum insulin, growth hormone and glucagon, but not in mean fasting cortisol. Changes with NET-EN started after 3 months, became maximal after 6 months and reverted to normal after 12 months of use, due to more frequent administration during the first 6 months of use (every 60 +/- 5 days) and to more spacing of the injections (every 84 +/- 5 days) after that. Changes with DMPA started after 3 months, and increased with the duration of use to become maximal after 12 months. Maximal changes were similar with DMPA and NET-EN and consisted of: a significant increase in fasting blood glucose and pyruvate and serum insulin; a significant increase in 2-hour blood glucose and pyruvate, serum insulin, growth hormone and glucagon. Although significant changes in blood glucose levels occurred with both DMPA and NET-EN, yet they did not reach the lower cut-off levels for impaired glucose tolerance in any user. With the same spacing of injections, i.e. every 84 +/- 5 days for NET-EN and every 90 +/- 5 days for DMPA, the effects on various parameters studied were less with NET-EN.

  10. Health-related quality of life advantage of long-acting injectable antipsychotic treatment for schizophrenia: a time trade-off study

    Directory of Open Access Journals (Sweden)

    Osborne Richard H

    2012-04-01

    Full Text Available Abstract Background This study was undertaken to estimate utility values for alternative treatment intervals for long acting antipsychotic intramuscular injections for the treatment of schizophrenia. Methods Vignettes were developed using the published literature and an iterative consultation process with expert clinicians and patient representative groups. Four vignettes were developed. The first was a vignette of relapsed/untreated schizophrenia. The other three vignettes presented a standardised picture of well-managed schizophrenia with variations in the intervals between injections: once every 2-weeks, 4-weeks and 3-months. A standardised time trade off (TTO approach was used to obtain utility values for the vignettes. As a societal perspective was sought, a representative sample of individuals from across the community (Sydney, Australia was recruited. Ninety-eight people completed the TTO interview. The vignettes were presented in random order to prevent possible ordering effects. Results A clear pattern of increasing utility was observed with increasing time between injections. Untreated schizophrenia was rated as very poor health-related quality of life with a mean (median utility of 0.27 (0.20. The treated health states were rated at much higher utilities and were statistically significantly different (p Conclusions This study has provided robust data indicating that approximately a 0.05 utility difference exists between treatment options, with the highest utility assigned to 3-monthly injections.

  11. Treatment patterns in Medicaid patients with schizophrenia initiated on a first- or second-generation long-acting injectable versus oral antipsychotic

    Directory of Open Access Journals (Sweden)

    Pilon D

    2017-03-01

    Full Text Available Dominic Pilon,1 Kruti Joshi,2 Neeta Tandon,2 Marie-Hélène Lafeuille,1 Rhiannon L Kamstra,1 Bruno Emond,1 Patrick Lefebvre2 1Groupe d’analyse, Ltée, Montréal, QC, Canada; 2Janssen Scientific Affairs, LLC, Titusville, NJ, USA Background: Poor antipsychotic (AP adherence is a key issue in patients with schizophrenia. First-generation antipsychotic (FGA and second-generation antipsychotic (SGA long-acting injectable therapies (LAI may improve adherence compared to oral antipsychotics (OAP. The objective of the study was to compare treatment adherence and persistence in Medicaid patients with schizophrenia initiated on first-generation long-acting injectable therapies (FGA-LAI or second-generation long-acting injectable therapies (SGA-LAI versus OAP.Methods: Adults with schizophrenia initiated on FGA-LAI, SGA-LAI, or OAP on or after January 2010 were identified using a six-state Medicaid database (January 2009– March 2015. Outcomes were assessed during the 12 months following treatment initiation. Index medication adherence was assessed using the proportion of days covered ≥80%, while persistence was assessed as no gap of ≥30, ≥60, or ≥90 days between days of supply. Outcomes were compared between FGA/SGA-LAI and OAP cohorts using chi-squared tests and adjusted odds ratios (OR.Results: During follow-up, AP polypharmacy was more common in FGA-LAI patients (N=1,089; 36%; P=0.029 and less common in SGA-LAI patients (N=2,209; 27%; P<0.001 versus OAP patients (N=20,478; 33%. After adjustment, SGA-LAI patients had 24% higher odds of adherence at 12 months (OR: 1.24; P<0.001, in contrast to FGA-LAI patients who had 48% lower odds of adherence (OR: 0.52; P<0.001 relative to OAP patients. SGA-LAI patients were more likely to be persistent (no gap ≥60 days at 12 months than OAP patients (37% vs 30%; P<0.001, but not FGA-LAI patients (31% vs 30%; P=0.776. In comparison to OAP patients, SGA-LAI patients had 46% higher adjusted odds of

  12. Long-Acting Diclofenac Ester Prodrugs for Joint Injection: Kinetics, Mechanism of Degradation, and In Vitro Release From Prodrug Suspension

    DEFF Research Database (Denmark)

    Mertz, Nina

    2016-01-01

    A prodrug approach for local and sustained diclofenac action after injection into joints based on ester prodrugs having a pH-dependent solubility is presented. Inherent ester prodrug properties influencing the duration of action include their pH-dependent solubility and charge state, as well...... as susceptibility to undergo esterase facilitated hydrolysis. In this study, physicochemical properties and pH rate profiles of 3 diclofenac ester prodrugs differing with respect to the spacer carbon chain length between the drug and the imidazole-based promoiety were determined and a rate equation for prodrug...... degradation in aqueous solution in the pH range 1-10 was derived. In the pH range 6-10, the prodrugs were subject to parallel degradation to yield diclofenac and an indolinone derivative. The prodrug degradation was found to be about 6-fold faster in 80% (vol/vol) human plasma as compared to 80% (vol...

  13. A qualitative study of experiences with and perceptions regarding long-acting injectable antipsychotics: Part I-patient perspectives.

    Science.gov (United States)

    Iyer, Srividya; Banks, Nicola; Roy, Marc-André; Tibbo, Phil; Williams, Richard; Manchanda, Rahul; Chue, Pierre; Malla, Ashok

    2013-05-01

    Objectif : Malgré le problème largement reconnu de la mauvaise observance des antipsychotiques (AP), les injectables à action prolongée (IAP) qui pourraient améliorer l’observance sont sous-utilisés au Canada. Les attitudes à l’égard des IAP chez les patients et les psychiatres peuvent contribuer à cette sous-utilisation. Notre objectif était d’enquêter sur les perceptions et les attitudes des patients à l’égard des IAP au Canada. Méthode : Des groupes de discussion ont été formés de 34 patients ayant reçu un diagnostic de psychose du spectre de la schizophrénie dans 4 provinces canadiennes. Les groupes de discussion portaient sur les expériences avec les AP IAP et les attitudes à leur égard. Les séances ont fait l’objet d’un enregistrement sonore et ont été transcrites textuellement, et ces transcriptions ont été codées à l’aide d’une combinaison de méthodes déductives et inductives. Résultats : Quatre thèmes se sont dégagés : conscience et connaissance des IAP; perceptions des IAP; considérations concernant le coût et la commodité; et les questions liées au contexte coercitif dans lequel les IAP sont souvent prescrits. Neuf patients n’avaient jamais entendu parler des IAP, et d’autres ont déclaré ne pas avoir compris lorsqu’on a discuté avec eux des IAP. Les patients avaient habituellement entendu parler des IAP dans un contexte soit de coercition, soit de non-observance des médicaments. Les patients avaient des perceptions positives et négatives à l’égard des IAP. Les perceptions positives étaient axées sur la prévention de la rechute et l’effort réduit pour maintenir l’observance, et les perceptions négatives portaient sur les coûts financiers et la complication des rendez-vous pour recevoir les injections. Conclusion : Afin d’accroître l’utilisation des IAP, il faut aborder certaines questions, notamment l’insuffisance de l’information donnée aux patients, l

  14. Clinical outcomes of long-acting injectable risperidone in patients with schizophrenia: six-month follow-up from the Electronic Schizophrenia Treatment Adherence Registry in Latin America

    Directory of Open Access Journals (Sweden)

    Mario Louzã

    2010-12-01

    Full Text Available Rogelio Apiquian1, Rodrigo Córdoba2, Mario Louzã31Americas University, Behavior and Development Sciences Division, Mexico City, Mexico; 2Nervous System Research Center-CISNE, Bogota, Colombia; 3Schizophrenia Research Program, Institute of Psychiatry, Faculty of Medicine, University of São Paulo, BrazilBackground: Risperidone long-acting injection (RLAI has been shown to be efficacious, improve compliance, and increase long-term retention rate on therapy. The aim of this work was to determine the effect of RLAI on clinical outcome and hospitalization rate in patients with schizophrenia or schizoaffective disorder enrolled in the electronic Schizophrenia Treatment Adherence Registry in Latin America.Methods: Data were collected at baseline, retrospectively for the 12 months prior to baseline, and prospectively every three months for 24 months. Hospitalization prior to therapy was assessed by a retrospective chart review. Efficacy and functioning were evaluated using Clinical Global Impression of Illness Severity (CGI-S, Personal and Social Performance (PSP, and Global Assessment of Functioning (GAF scores. Relapse and treatment were also registered.Results: Patients were recruited in Mexico (n = 53, Brazil (n = 11, and Colombia (n = 15. Sixty-five percent (n = 52 were male, and mean age was 32.9 years. Patients were classified as having schizophrenia (n = 73 or schizoaffective disorder (n = 6. The mean dose of RLAI at six months was 34.1 mg (standard deviation = 10.2 mg. The percentage of hospitalized patients before treatment was 28.2% and 5.1% at six months after initiating RLAI (P < 0.001. Significant changes were registered on CGI-S, GAF, and PSP scores.Conclusions: RLAI was associated with an improvement in clinical symptoms and functioning, and a greater reduction in hospitalization.Keywords: long-acting, risperidone, schizophrenia, schizoaffective disorder, Latin America

  15. Medication adherence in patients with psychotic disorders: an observational survey involving patients before they switch to long-acting injectable risperidone.

    Science.gov (United States)

    Baylé, Franck Jean; Tessier, Arnaud; Bouju, Sophie; Misdrahi, David

    2015-01-01

    Maintaining antipsychotic therapy in psychosis is important in preventing relapse. Long-acting depot preparations can prevent covert non-adherence and thus potentially contribute to better patient outcomes. In this observational survey the main objective is to evaluate medication adherence and its determinants for oral treatment in a large sample of patients with psychosis. In this cross-sectional survey medication adherence for oral treatment was assessed by patients using the patient-rated Medication Adherence Questionnaire (MAQ). Data were collected by physicians on patients with a recent acute psychotic episode before switching to long-acting injectable risperidone. Other evaluations included disease severity (Clinical Global Impression - Severity), patients' insight (Positive and Negative Syndrome Scale item G12), treatment acceptance (clinician-rated Compliance Rating Scale), and therapeutic alliance (patient-rated 4-Point ordinal Alliance Scale). A total of 399 psychiatrists enrolled 1,887 patients (mean age 36.8±11.9 years; 61.6% had schizophrenia). Adherence to oral medication was "low" in 53.2% of patients, "medium" in 29.5%, and "high" in 17.3%. Of patients with psychiatrist-rated active acceptance of treatment, 70% had "medium" or "high" MAQ scores (Padherence was significantly associated with therapeutic alliance (4-Point ordinal Alliance Scale score; PPatient age was significantly associated with adherence: mean age increased with greater adherence (35.6, 36.7, and 38.6 years for patients with "low", "medium", and "high" levels of adherence, respectively; P=0.0007), while age adherence was also associated with a diagnosis of schizophrenia (P=0.0083), more severe disease (Clinical Global Impression - Severity ≥4; Padherence was low in most patients, with a strong positive association between self-reported adherence and psychiatrists' assessment of treatment acceptance. Understanding factors associated with poor medication adherence may help

  16. A New Level A Type IVIVC for the Rational Design of Clinical Trials Toward Regulatory Approval of Generic Polymeric Long-Acting Injectables.

    Science.gov (United States)

    Somayaji, Mahadevabharath R; Das, Debarun; Przekwas, Andrzej

    2016-10-01

    Chronic neuropsychiatric disorders and diabetes mellitus affect millions of patients and require long-term supervision and expensive medical care. Although repeated drug administration can help manage these diseases, relapses and re-hospitalization owing to patient non-adherence and reduced therapeutic efficacy remain challenging. In response, long-acting injectables, which provide sustained drug release over longer periods at concentrations close to therapeutic ranges, have been proposed. Recent advancements include polymeric long-acting injectables (pLAIs), in which the active pharmaceutical ingredient (API) is encapsulated within U.S. Food and Drug Administration (FDA)-approved biocompatible polymers, such as poly(lactic-co-glycolic acid), or PLGA. Despite significant progress and development in the global pLAI market, FDA guidance for the approval of complex drug products, such as generic pLAIs, is not clearly defined. Although in vitro to in vivo correlation (IVIVC) can facilitate the identification of critical quality attributes (CQAs), drug formulations, and in vitro test platforms for evaluating drug performance in vivo, the application of IVIVC in order to shortlist time- and resource-intensive clinical trials for generic pLAIs has not been reported. Here, we propose a new Level A Type IVIVC that directly correlates the in vitro outcomes, such as drug dissolution, of candidate generic formulations with the clinical characteristics, such as drug absorption, of a reference listed drug (RLD), to help identify the specific generic pLAI formulations with clinical absorptions that are likely to be similar to that of the RLD, thereby reducing the number of clinical trials required for evaluation of clinical bioequivalence (BE). Therefore, the scope of the proposed method is intended only for the rational design of clinical trials, i.e., to shortlist the specific pLAI generic formulations for clinical BE evaluation, and not necessarily to analyze drug performances

  17. Persistent efficacy of a long acting injectable formulation of moxidectin against natural infestations of the sheep nasal bot (Oestrus ovis) in Spain.

    Science.gov (United States)

    Rugg, Douglas; Ferrer, Luis Miguel; Sarasola, Patxi; Figueras, Luis; Lacasta, Delia; Liu, Bo; Bartram, David

    2012-09-10

    Cydectin(®) 2% LA Solution for Injection for Sheep (Pfizer Animal Health) is a long-acting (LA) formulation of moxidectin for the treatment and prevention of mixed infections of gastro-intestinal nematodes, respiratory nematodes and certain arthropod parasites in sheep. To evaluate the duration of persistent efficacy against nasal bots (Oestrus ovis), a natural exposure study was conducted in Spain during the summer of 2011. One hundred and twenty nasal bot-free, Rasa Aragonesa sheep were randomly allocated to eight groups of 15 animals each. On Day 0, four groups were treated at the recommended dose rate of 1 mg moxidectin/kg bodyweight. Four groups remained untreated as negative controls. All animals were held in nasal bot-proof housing except for exposure to natural challenge when one group of treated sheep and one of group of control animals were transferred to a local pasture at either 0-20, 20-40, 40-60, or 60-80 days after treatment. Following challenge, sheep were scored for clinical signs of bot infestation, necropsied and the heads sectioned for larval recovery. Nasal bot larvae were retrieved from 7 to 11 control sheep following each exposure period indicating that adult bots were active throughout the study. In the first challenge up to 20 days after treatment, when sheep were slaughtered immediately after exposure, the majority of larvae were first instar (L1) and only 3 of the 15 control sheep were infested with second instars (L2). There was 100% efficacy against L2 and 38.1% reduction in the number of live L1 in the treated sheep but mean counts were not significantly different between treatment and control groups (P ≥ 0.05). For the subsequent exposure periods 20-80 days after treatment (necropsies 7-9 days after challenge), 6-10 sheep were infested with L1 and 9-11 control sheep were infested with L2 and third instars (L3). There was negligible efficacy against L1, but treatment with moxidectin resulted in 100% control of L2 and L3. These

  18. Incidence and time course of extrapyramidal symptoms with oral and long-acting injectable paliperidone: a posthoc pooled analysis of seven randomized controlled studies

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    Gopal S

    2013-09-01

    Full Text Available Srihari Gopal,1 Yanning Liu,1 Larry Alphs,2 Adam Savitz,1 Isaac Nuamah,1 David Hough1 1Janssen Research and Development, LLC, Raritan, 2Janssen Scientific Affairs, LLC, Titusville, NJ, USA Background: The purpose of this study was to compare incidence rates and time course of extrapyramidal symptom (EPS-related treatment-emergent adverse events (TEAEs between oral and long-acting injectable (LAI paliperidone. Methods: The analysis included pooled data (safety analysis set, 2,256 antipsychotic-treated and 865 placebo-treated patients with schizophrenia from seven randomized, double-blind, placebo-controlled paliperidone studies (three oral [6 weeks each] and four LAI [9–13 weeks] and assessed comparable doses (oral, 3–15 mg; LAI, 25–150 mg eq. [US doses 39–234 mg]. We summarized incidence rates and time of onset for EPS-related TEAE, categorized by EPS group terms, ie, tremor, dystonia, hyperkinesia, parkinsonism, and dyskinesia, and use of anti-EPS medication. Mean scores over time for the Abnormal Involuntary Movement Scale (AIMS, for dyskinesia, Barnes Akathisia Rating Scale (BARS, for akathisia, and Simpson Angus Rating Scale (SAS, for parkinsonism were graphed. Results: Incidence rates for all categories of spontaneously reported EPS-related TEAEs except for hyperkinesia, were numerically lower in pooled LAI studies than in pooled oral studies. Highest rates were observed in the first week of paliperidone-LAI (for all EPS symptoms except dyskinesia and oral paliperidone treatment (except parkinsonism and tremor. Anti-EPS medication use was significantly lower in LAI (12% versus oral studies (17%, P = 0.0035. Mean values for EPS scale scores were similar between LAI and oral treatment at endpoint, and no dose response was evident. Mean reductions (standard deviation from baseline to endpoint in EPS scale scores were larger for LAI (AIMS, −0.10 [1.27]; BARS, −0.09 [1.06]; SAS, −0.04 [0.20] versus oral studies (AIMS, −0.08 [1

  19. Ethical issues experienced by mental health nurses in the administration of antipsychotic depot and long-acting intramuscular injections: a qualitative study.

    Science.gov (United States)

    Smith, James Paul; Herber, Oliver Rudolf

    2015-06-01

    The ethical issues experienced by mental health nurses in administering antipsychotic depot and long-acting intramuscular injections (LAI) were explored in the present study. Mental health nurses face ethically-difficult situations when administering these medications. A phenomenological research method guided by Max van Manen's human science approach describes and interprets the ethical issues involved in performing the procedure. Purposive and snowball sampling was used to select eight participants from two mental health hospitals. Semistructured interviews were carried out to collect data. A thematic analysis was conducted on the data. The four main themes that emerged from the analyses were: (i) lack of alternatives; (ii) safety; (iii) feeling uncomfortable; and (iv) difficulty maintaining the therapeutic relationship. The findings suggest that mental health nurses face ethical challenges in administering LAI. The findings raise much needed awareness of the need for mental health nurses and nurse educators to consider the ethical issues experienced while performing the procedure. There is a need for nurse education providers and organizations to provide opportunities for mental health nurses to address their 'lived experiences'. Educational courses are needed to equip mental health nurses with the technical and critical thinking skills to administer safe and effective antipsychotic depot and LAI.

  20. Clinical outcomes of long-acting injectable risperidone in patients with schizophrenia: six-month follow-up from the Electronic Schizophrenia Treatment Adherence Registry in Latin America

    Science.gov (United States)

    Apiquian, Rogelio; Córdoba, Rodrigo; Louzã, Mario

    2011-01-01

    Background Risperidone long-acting injection (RLAI) has been shown to be efficacious, improve compliance, and increase long-term retention rate on therapy. The aim of this work was to determine the effect of RLAI on clinical outcome and hospitalization rate in patients with schizophrenia or schizoaffective disorder enrolled in the electronic Schizophrenia Treatment Adherence Registry in Latin America. Methods Data were collected at baseline, retrospectively for the 12 months prior to baseline, and prospectively every three months for 24 months. Hospitalization prior to therapy was assessed by a retrospective chart review. Efficacy and functioning were evaluated using Clinical Global Impression of Illness Severity (CGI-S), Personal and Social Performance (PSP), and Global Assessment of Functioning (GAF) scores. Relapse and treatment were also registered. Results Patients were recruited in Mexico (n = 53), Brazil (n = 11), and Colombia (n = 15). Sixty-five percent (n = 52) were male, and mean age was 32.9 years. Patients were classified as having schizophrenia (n = 73) or schizoaffective disorder (n = 6). The mean dose of RLAI at six months was 34.1 mg (standard deviation = 10.2 mg). The percentage of hospitalized patients before treatment was 28.2% and 5.1% at six months after initiating RLAI (P < 0.001). Significant changes were registered on CGI-S, GAF, and PSP scores. Conclusions RLAI was associated with an improvement in clinical symptoms and functioning, and a greater reduction in hospitalization. PMID:21326651

  1. Clinical outcomes with olanzapine long-acting injection: impact of the 3-hour observation period on patient satisfaction and well-being

    OpenAIRE

    Anand E; Berggren L; Landry J; Tóth Á; Detke HC

    2016-01-01

    Ernie Anand,1 Lovisa Berggren,2 John Landry,3 Ágoston Tóth,4 Holland C Detke5 1Neuroscience Medical Affairs, Eli Lilly & Company Ltd, Windlesham, UK; 2Global Statistical Sciences, Lilly Deutschland GmbH, Bad Homburg, Germany; 3Global Statistical Sciences, Eli Lilly Canada Inc., Toronto, ON, Canada; 4Neuroscience, Lilly Hungary, Budapest, Hungary; 5Psychiatry and Pain Disorders, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA Background...

  2. Medication adherence in patients with psychotic disorders: an observational survey involving patients before they switch to long-acting injectable risperidone

    Directory of Open Access Journals (Sweden)

    Baylé FJ

    2015-09-01

    Full Text Available Franck Jean Baylé,1 Arnaud Tessier,2,3 Sophie Bouju,4 David Misdrahi2,3 1Sainte-Anne Hospital (SHU, Paris V-Descartes University, Paris, 2Hôpital Charles Perrens, Pôle de Psychiatrie Adulte, 3CNRS UMR 5287-INCIA, Bordeaux University, Bordeaux, 4Janssen-Cilag France, Issy Les Moulineaux, Paris, France Background: Maintaining antipsychotic therapy in psychosis is important in preventing relapse. Long-acting depot preparations can prevent covert non-adherence and thus potentially contribute to better patient outcomes. In this observational survey the main objective is to evaluate medication adherence and its determinants for oral treatment in a large sample of patients with psychosis.Methods: In this cross-sectional survey medication adherence for oral treatment was assessed by patients using the patient-rated Medication Adherence Questionnaire (MAQ. Data were collected by physicians on patients with a recent acute psychotic episode before switching to long-acting injectable risperidone. Other evaluations included disease severity (Clinical Global Impression – Severity, patients’ insight (Positive and Negative Syndrome Scale item G12, treatment acceptance (clinician-rated Compliance Rating Scale, and therapeutic alliance (patient-rated 4-Point ordinal Alliance Scale.Results: A total of 399 psychiatrists enrolled 1,887 patients (mean age 36.8±11.9 years; 61.6% had schizophrenia. Adherence to oral medication was “low” in 53.2% of patients, “medium” in 29.5%, and “high” in 17.3%. Of patients with psychiatrist-rated active acceptance of treatment, 70% had “medium” or “high” MAQ scores (P<0.0001. Medication adherence was significantly associated with therapeutic alliance (4-Point ordinal Alliance Scale score; P<0.0001. Patient age was significantly associated with adherence: mean age increased with greater adherence (35.6, 36.7, and 38.6 years for patients with “low”, “medium”, and “high” levels of adherence

  3. 长效土霉素注射液在猪体内的药动学及相对生物利用度研究%Pharmacokinetics and Relatively Bioavailability of Oxytetracycline Long Acting Injection in Swine

    Institute of Scientific and Technical Information of China (English)

    廖雪玲; 张炳旭; 丁焕中

    2012-01-01

    The pharmacokinetics and relatively bioavailability of oxytetracycline long acting injection were investigated in 7 healthy swine by a random cross experimental design. Animals were intramuscularly administrated 30% oxytetracycline long acting injection and 20% terramycin long acting injection, all at the single dose of 20 mg/kg body weight. The plasma concentrations of oxytetracycline were determined by HPLC method. The plasma concentration- time data obtained from experiments were analyzed using MCPKP program. The main pharmacokinetic parameters for 30% terramycin long acting injection and 20% terramycin long acting injection administrated intramuscularly were as follows respectively: tl/EKa (0. 088 ± 0.016) and (0. 140 ± 0. 076) h, t1/2β (52.499 ±22.885) and (36.481 ±21.673) h, Tmax(0.609 _0. 100) and (0.832 ±0.373) h, Cmax(4. 956 ± 1.171) and (5.018 ±0.948) μg/mL, AUC (112.483 ±18. 135) and (109.877±19.949) mg/L · h,F(105.368 ±26.027)%. These results showed that there was no signifi pharmacokinetic parameters of 30% oxytetracycline long acting injection and 20%%对7头健康猪随机交叉设计进行单剂量肌肉注射国产30%长效土霉素注射液和进口20%长效土霉素注射液药动学试验,给药剂量以土霉素计均为20mg/kg体重。用高效液相色谱法测定血药浓度,血药浓度一时间数据用MCPKP计算机程序处理。30%长效土霉素注射液和20%长效土霉素注射液主要药动学参数分别为:吸收半衰期(t1/2ka)为(0.088±0.016)、(0.140±0.076)h;消除半衰期(t1/2β)为(52.499±22.885)、(36.481±21.673)h;达峰时间(Lmax)为(0.609±0.100)、(0.832±0.373)h;峰浓度(Cmax)为(4.956±1.171)、(5.0184-0.948)μg/mL;药时曲线下面积(AUG)为(112.483±18.135)、(109.877±19.949)mg/L·h;以20%长效土霉素注射液为对照物,30%长效土霉素注射液

  4. Postmortem redistribution of olanzapine following intramuscular administration of olanzapine pamoate in dogs.

    Science.gov (United States)

    Johnson, Jason T; Everly, Amy G; Kpakima, Felicia E Frazier; Detke, Holland C

    2015-12-01

    The potential for postmortem redistribution of olanzapine was investigated in beagle dogs. Olanzapine pamoate monohydrate was administered once every 14 days by intramuscular injection for 3 months to fed male dogs (n=15) at a dose of 20 mg/kg olanzapine (equivalent to 46 mg/kg olanzapine pamoate monohydrate). Blood samples were collected after the fifth (Day 57) and sixth (Day 71) doses to determine olanzapine and N-oxide olanzapine concentrations. On Day 71 at 72 h postdose, dogs were euthanized and placed on their backs without additional manipulation and held for postmortem blood, urine, and tissue collection at room temperature for up to 168 h postdose (96 h after euthanasia). Concentrations of olanzapine and N-oxide olanzapine were determined by liquid chromatography-mass spectroscopy/mass spectroscopy (LC-MS/MS). Postmortem olanzapine concentrations in blood increased up to seven-fold compared to the last quantified antemortem blood concentration. Olanzapine concentrations in vein tissue samples (surrogates for peripheral blood) also increased, whereas other tissue concentrations, such as myocardium, lung, liver, and kidney decreased over the postmortem period. An increase in blood concentration of olanzapine after death was observed in all but one animal, suggesting that postmortem redistribution may occur in dogs following biweekly intramuscular administration of olanzapine pamoate monohydrate. The rise in olanzapine concentrations in blood after death in this study may potentially be attributed to diffusion from multiple tissues to blood and, to a lesser extent, reduction of the N-oxide olanzapine metabolite back to olanzapine. However, the generalizability of these results to humans cannot be confirmed by the present study.

  5. Delirium with anticholinergic symptoms after a combination of paliperidone and olanzapine pamoate in a patient known to smoke cannabis: an unfortunate coincidence.

    Science.gov (United States)

    Kokalj, Anja; Rijavec, Nikolina; Tavčar, Rok

    2016-06-22

    We report a case of delirium with anticholinergic symptoms in a 19-year-old female patient with schizophrenia. On the day the symptoms emerged, the patient received olanzapine long-acting injection and a higher dose of paliperidone. We observed symptoms ranging from confusion to delirium as well as some anticholinergic symptoms. The delirium lasted 24 hours and was managed by intravenous fluid substitution and oral benzodiazepines. Olanzapine pamoate, paliperidone and cannabis are central nervous system (CNS) depressants, and their combination can increase the risks of CNS depression. In this case report, we review the symptoms of delirium in a case of antipsychotic overdose and provide general guidelines for managing these symptoms. We also review possible complications in combined use of cannabis, olanzapine and paliperidone. 2016 BMJ Publishing Group Ltd.

  6. Acute camptocormia induced by olanzapine: a case report

    Directory of Open Access Journals (Sweden)

    Boyer Stéphane

    2010-06-01

    Full Text Available Abstract Introduction Camptocormia refers to an abnormal posture with flexion of the thoraco-lumbar spine which increases during walking and resolves in supine position. This symptom is an increasingly recognized feature of parkinsonian and dystonic disorders, but may also be caused by neuromuscular diseases. There is recent evidence that both central and peripheral mechanisms may be involved in the pathogenesis of camptocormia. We report a case of acute onset of camptocormia, a rare side effect induced by olanzapine, a second-generation atypical anti-psychotic drug with fewer extra-pyramidal side-effects, increasingly used as first line therapy for schizophrenia, delusional disorders and bipolar disorder. Case presentation A 73-year-old Caucasian woman with no history of neuromuscular disorder, treated for chronic delusional disorder for the last ten years, received two injections of long-acting haloperidol. She was then referred for fatigue. Physical examination showed a frank parkinsonism without other abnormalities. Routine laboratory tests showed normal results, notably concerning creatine kinase level. Fatigue was attributed to haloperidol which was substituted for olanzapine. Our patient left the hospital after five days without complaint. She was admitted again three days later with acute back pain. Examination showed camptocormia and tenderness in paraspinal muscles. Creatine kinase level was elevated (2986 UI/L. Magnetic resonance imaging showed necrosis and edema in paraspinal muscles. Olanzapine was discontinued. Pain resolved quickly and muscle enzymes were normalized within ten days. Risperidone was later introduced without significant side-effect. The camptocormic posture had disappeared when the patient was seen as an out-patient one year later. Conclusions Camptocormia is a heterogeneous syndrome of various causes. We believe that our case illustrates the need to search for paraspinal muscle damage, including drug

  7. Costs and effects of long-acting risperidone compared with oral atypical and conventional depot formulations in Germany.

    Science.gov (United States)

    Laux, Gerd; Heeg, Bart; van Hout, Ben A; Mehnert, Angelika

    2005-01-01

    Schizophrenia is one of the most expensive psychiatric conditions because of high direct and indirect costs associated with the nature of the illness, its resistance to treatment and the consequences of relapse. Long-acting risperidone is a new formulation of an atypical antipsychotic drug that also offers the improvements in compliance associated with haloperidol depot. The aim of this simulation study was to compare the benefits and costs of three pharmacological treatment strategies comprising first-line treatment with long-acting risperidone injection, a haloperidol depot or an oral atypical antipsychotic agent, over a 5-year period in Germany. A discrete event simulation model was developed to compare three treatment scenarios from the perspective of major third-party payers (sickness funds and social security 'Sozialversicherung'). The scenarios comprised first-line treatment with haloperidol depot (scenario 1), long-acting risperidone (scenario 2) and oral olanzapine (scenario 3). Switches to second or third-line options were allowed when side-effects occurred or a patient suffered more than a fixed number of relapses. The model accounted for fixed patient characteristics, and on the basis of these, simulated patient histories according to several time-dependent variables. The time horizon for this model was limited to 5 years, and in accordance with German guidelines, costs and effects were discounted by between 3 and 10%. Direct costs included medication, type of physician visits and treatment location. Indirect costs were not included. Information on treatment alternatives, transition probabilities, model structure and healthcare utilization were derived from the literature and an expert panel. Outcomes were expressed in terms of the number and duration of psychotic episodes, cumulative symptom scores, costs, and quality-adjusted life-years (QALY). Univariate sensitivity analyses were carried out, as were subgroup analyses based on disease severity and

  8. Relative bioavailability and safety of aripiprazole lauroxil, a novel once-monthly, long-acting injectable atypical antipsychotic, following deltoid and gluteal administration in adult subjects with schizophrenia.

    Science.gov (United States)

    Turncliff, Ryan; Hard, Marjie; Du, Yangchun; Risinger, Robert; Ehrich, Elliot W

    2014-11-01

    Aripiprazole lauroxil is a linker lipid ester of aripiprazole for extended-release intramuscular (IM) injection. This multicenter, randomized, open-label study evaluated the pharmacokinetics (PK), relative bioavailability, and tolerability of a single IM deltoid or gluteal injection of aripiprazole lauroxil in adult subjects with chronic stable schizophrenia or schizoaffective disorder. Forty-six subjects were randomized 1:1 to aripiprazole lauroxil 441 mg IM in the deltoid or gluteal muscle. Samples were collected through 89 days post-dose to measure levels of aripiprazole lauroxil, N-hydroxymethyl aripiprazole, aripiprazole, and dehydro-aripiprazole. Forty-three (93.5%) subjects completed all study assessments; most were CYP2D6 extensive or immediate metabolizers (96%); two (4%) were poor metabolizers. The PK of aripiprazole following aripiprazole lauroxil was characterized by a steady rise in plasma concentrations (Tmax 44-50 days), a broad peak, and prolonged exposure attributable to the dissolution of aripiprazole lauroxil and formation rate-limited elimination of aripiprazole (t1/2=15.4-19.2 days). Deltoid vs. gluteal administration resulted in slightly higher Cmax aripiprazole concentrations [1.31 (1.02, 1.67); GMR 90% CI]; total exposure (AUCinf) was similar between sites of administration [0.84 (0.57, 1.24)]. N-hydroxymethyl-aripiprazole and dehydro-aripiprazole exposures were 10% and 33-36%, respectively, of aripiprazole exposure following aripiprazole lauroxil. The most common adverse events were injection site pain in 20 subjects (43.5%) and headache in 6 subjects (13.0%) of mild intensity occurring at a similar rate with deltoid and gluteal administration. Exposure ranges with deltoid and gluteal administration overlapped, suggesting that these sites may be used interchangeably. Despite a higher incidence of adverse events, deltoid muscle provides a more accessible injection site and could facilitate patient acceptance.

  9. Effect of subcutaneous injection of a long-acting analogue of somatostatin (SMS 201-995) on plasma thyroid-stimulating hormone in normal human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, S.; Tanaka, K.; Kumagae, M.; Takeda, F.; Morio, K.; Kogure, M.; Hasegawa, M.; Horiuchi, T.; Watabe, T.; Miyabe, S.

    1988-01-01

    SMS 201-995 (SMS), a synthetic analogue of somatostatin (SRIF) has been shown to be effective in the treatment of the hypersecretion of hormones such as in acromegaly. However, little is known about the effects of SMS on the secretion of thyroid-stimulating hormone (TSH) in normal subjects. In this study, plasma TSH was determined with a highly sensitive immunoradiometric assay, in addition to the concentration of SMS in plasma and urine with a radioimmunoassay, following subcutaneous injection of 25, 50, 100 ..mu..g of SMS or a placebo to normal male subjects, at 0900 h after an overnight fast. The plasma concentrations of SMS were dose-responsive and the peak levels were 1.61 +/- 0.09, 4.91 +/- 0.30 and 8.52 +/- 1.18 ng/ml, which were observed at 30, 15 and 45 min after the injection of 25, 50, and 100 ..mu..g of SMS, respectively. Mean plasma disappearance half-time of SMS was estimated to be 110 +/- 3 min. Plasma TSH was suppressed in a dose dependent manner and the suppression lasted for at least 8 hours. At 8 hours after the injection of 25, 50, and 100 ..mu..g of SMS, the plasma TSH levels were 43.8 +/- 19.4, 33.9 +/- 9.4 and 24.9 +/- 3.2%, respectively, of the basal values.

  10. Long-Acting Growth Hormone: An Update.

    Science.gov (United States)

    Saenger, Paul H; Mejia-Corletto, Jorge

    2016-01-01

    After the introduction of recombinant human growth hormone (rhGH) in 1985, a myriad of children and adults have benefited from its growth-promoting and metabolic effects. Nowadays, current therapeutic regimens rely on daily subcutaneous GH injections that could be burdensome and inconvenient to pediatric patients. As expected with any long-term parenteral pharmacological treatment, these daily regimens may promote nonadherence, poor compliance, treatment abandonment and/or suboptimal clinical outcomes. In order to improve patient and caregiver acceptance of proposed regimens, simplified dosing schedules could potentially aid in reducing poor compliance and maximize the therapeutic end results. Long-acting GH formulations have been designed and perfected over the last two decades, and currently there are several formulations in advanced stages of research as a reasonable attempt to improve patient's adherence to GH treatment. A long-acting GH preparation allowing for reduced injection frequency is likely to improve treatment adherence and to decrease the distress and inconvenience associated with daily injections. This review presents an update about the status of current and recent efforts that have enabled the formulation of sustained-release, long-acting rhGH as it has been longed for many years in the pediatric endocrinology field.

  11. Profile of paliperidone palmitate once-monthly long-acting injectable in the management of schizophrenia: long-term safety, efficacy, and patient acceptability – a review

    Directory of Open Access Journals (Sweden)

    González-Rodríguez A

    2015-05-01

    Full Text Available Alexandre González-Rodríguez,1 Rosa Catalán,1–4 Rafael Penadés,1–4 Clemente Garcia-Rizo,1,3,4 Miquel Bioque,1,4 Eduard Parellada,1,3–5 Miquel Bernardo1–4 1Barcelona Clinic Schizophrenia Unit (BCSU, Neuroscience Institute, Hospital Clinic of Barcelona, 2Department of Psychiatry and Clinical Psychobiology, University of Barcelona, 3Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS, Barcelona, Spain; 4Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM, Madrid, Spain; 5Department of Pharmacology, University of Barcelona, Barcelona, Spain Background and objectives: Short-term studies focused on once-monthly paliperidone palmitate (PP at doses of 25 mg eq, 50 mg eq, 75 mg eq, 100 mg eq, or 150 mg eq have shown its efficacy and tolerability in the treatment of schizophrenia patients. However, few open-label and long-term studies are available regarding this new pharmacological formulation. Thus, our main aim was to review the scientific evidence on efficacy, safety, tolerability, and preference of PP in these populations. Method: Electronic searches were conducted by using PubMed and ISI Web of Knowledge databases. All relevant studies published from 2009 until January 2015 were included without any language restriction if patients met diagnostic criteria for schizophrenia, and adequate information on efficacy, safety, and tolerability of once-monthly PP was available. Results: Nineteen studies were identified irrespective of the study design and duration of the follow-up period. Randomized, double-blind, placebo-controlled trials found that schizophrenia patients receiving PP showed a significant improvement in psychotic symptoms and similar adverse events compared to placebo and suggested that all doses of PP were efficacious and well tolerated. Other studies demonstrated noninferiority of PP compared to risperidone long-acting injectable in recently diagnosed schizophrenia patients, chronically

  12. Onset of efficacy with acute long-acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia: post hoc analysis of a randomized, double-blind clinical trial

    Directory of Open Access Journals (Sweden)

    Ma Yi-Wen

    2011-04-01

    Full Text Available Abstract Background This post hoc analysis (trial registration: ClinicalTrials.gov NCT00590577 assessed onset of efficacy and tolerability of acute treatment with once-monthly paliperidone palmitate (PP, a long-acting atypical antipsychotic initiated by day 1 and day 8 injections, in a markedly to severely ill schizophrenia population. Methods Subjects entering the 13-week, double-blind trial were randomized to PP (39, 156, or 234 mg [25, 100, and 150 mg eq of paliperidone, respectively] or placebo. This subgroup analysis included those with a baseline Clinical Global Impressions-Severity (CGI-S score indicating marked to severe illness. PP subjects received a 234-mg day 1 injection (deltoid, followed by their assigned dose on day 8 and monthly thereafter (deltoid or gluteal. Thus, data for PP groups were pooled for days 4 and 8. Measures included Positive and Negative Syndrome Scale (PANSS, CGI-S, Personal and Social Performance (PSP, and adverse events (AEs. Analysis of covariance (ANCOVA and last-observation-carried-forward (LOCF methodologies, without multiplicity adjustments, were used to assess changes in continuous measures. Onset of efficacy was defined as the first time point a treatment group showed significant PANSS improvement (assessed days 4, 8, 22, 36, 64, and 92 versus placebo, which was maintained through end point. Results A total of 312 subjects met inclusion criterion for this subgroup analysis. After the day 1 injection, mean PANSS total scores improved significantly with PP (all received 234 mg versus placebo at day 4 (P = 0.012 and day 8 (P = 0.007. After the day 8 injection, a significant PANSS improvement persisted at all subsequent time points in the 234-mg group versus placebo (P P P P Conclusions In this markedly to severely ill population, acute treatment with 234 mg PP improved psychotic symptoms compared with placebo by day 4. After subsequent injections, observed improvements are suggestive of a dose

  13. 利培酮微球和利培酮治疗精神分裂症对照研究%A comparative study of risperidone long-acting injection and risperidone in treatment for patients with schizophrenia

    Institute of Scientific and Technical Information of China (English)

    苏磊; 孙自豪; 冯凡; 李龙飞

    2015-01-01

    Objective To explore the efficacy and safety of risperidone long-acting injection and risperidone in treatment for patients with schizophrenia.Methods A total of 160 patients with schizophrenia were randomly divided into study group ( 80 cases) with risperidone long-acting injection and control group(80 cases) with risperidone for treatment of 3 months.They were assessed with Positive and Negative Syndrome Scale(PANSS), Clinical Global Impression-Severity of Illness(CGI-S), Clinical Global Impression-Global Improvement(CGI-I) and Extrapyramidal Symptom Rating Scale(ESRS) at baseline , 1st month end, 2nd month end and 3rd month end of treatment.Results At 1st month end, 2nd month end and 3rd month end of treatment, the factors and total scores of PANSS in two groups were all significantly lower than those at baseline(P<0.05).At 2nd month end and 3rd month end of treatment, the factors and total scores of PANSS and CGI in study group were all significantly lower than those in control group(P<0.05).At 1st month end, 2nd month end and 3rd month end of treatment, the scores of ESRS in study group were significantly lower than those in control group(P<0.05).Conclusion It’s effective and safe for risperidone long-acting injection to treat the patients with schizophrenia.%目的:探寻利培酮微球和利培酮治疗精神分裂症患者的疗效和安全性。方法将160例精神分裂症患者随机分为研究组和对照组各80例,研究组用利培酮微球系统治疗,对照组用利培酮系统治疗,共3个月,在基线和治疗后1、2、3个月末应用阳性和阴性综合征量表( PANSS)、临床疗效总评量表-病情严重程度( CGI-S)、临床疗效总评量表-疗效总评( CGI-I)、锥体外系症状评定量表( ESRS)评价。结果两组在治疗后第1、2、3个月末的PANSS评分均低于基线时相应评分(P<0.05)。在治疗后第2、3个月末,研究组PANSS评分以及CGI

  14. 长效盐酸多西环素注射液在猪体内残留的消除规律%Residual elimination of long-acting doxycycline hydrochloride injection in swines

    Institute of Scientific and Technical Information of China (English)

    李媚; 刘伟坚; 黄显会; 曾振灵

    2011-01-01

    在常规饲养条件下,对35头健康成年猪按10 mg/kg体质量的剂量肌肉注射10%长效盐酸多西环素注射液,给药2次,给药间隔时间为48 h.第2次给药后12 h及2、5、9、14、19、25 d分别屠宰5头猪,分别采取每头猪的肌肉、肝脏、肾脏、皮肤+脂肪和注射位点肌肉等5种组织,用高效液相色谱法进行残留量测定.结果表明:在第2次给药后19 d,多西环素在各组织均能检测到,且残留均低于残留限量.多西环素残留浓度大小顺序:注射部位>肾脏>肝脏>皮脂>肌肉.采用WT1.4软件制定的统计方法来处理猪组织中药物浓度-时间数据,以制定休药期.%In routine breeding conditions, 35 healthy adult pigs were randomly divided into seven groups, 5 pigs each group. The long-acting doxycycline hydrochloride injection was administered intramuscularly at a dose of 10 mg/kg.Five pigs were sacrificed with exsanguinations at 12 h,2,5,9,14,19 and 25 d after last administration, and samples of rump muscle, injection site, liver, kidney and abdominal fat were collected. The doxycycline concentrations in muscle, injection site, liver, kidney and skint were determined by HPLC method. Tissue residues of doxycycline was below the maximum residue limit (MRL) after 19 days. In all of the detected tissues, injection site had the highest concentration,and then followed by kidney, liver and fat, while muscle had the lowest concentration. The concentration-time data of doxycycline were analyzed by WT1.4 software to get the WDT.

  15. Status of long-acting-growth hormone preparations--2015.

    Science.gov (United States)

    Høybye, Charlotte; Cohen, Pinchas; Hoffman, Andrew R; Ross, Richard; Biller, Beverly M K; Christiansen, Jens Sandahl

    2015-10-01

    Growth hormone (GH) treatment has been an established therapy for GH deficiency (GHD) in children and adults for more than three decades. Numerous studies have shown that GH treatment improves height, body composition, bone density, cardiovascular risk factors, physical fitness and quality of life and that the treatment has few side effects. Initially GH was given as intramuscular injections three times per week, but daily subcutaneous injections were shown to be more effective and less inconvenient and the daily administration has been used since its introduction in the 1980s. However, despite ongoing improvements in injection device design, daily subcutaneous injections remain inconvenient, painful and distressing for many patients, leading to noncompliance, reduced efficacy and increased health care costs. To address these issues a variety of long-acting formulations of GH have been developed. In this review we present the current status of long-acting GH preparations and discuss the specific issues related to their development.

  16. Pharmacogenetics of olanzapine metabolism.

    Science.gov (United States)

    Söderberg, Mao Mao; Dahl, Marja-Liisa

    2013-08-01

    The pharmacokinetics of the atypical antipsychotic, olanzapine, display large interindividual variation leading to multiple-fold differences in drug exposure between patients at a given dose. This variation in turn gives rise to the need for individualized dosing in order to avoid concentration-dependent adverse effects or therapeutic failure. Genetically determined differences in olanzapine metabolism represent a less studied source of variability in comparison to environmental and physiological factors. In this review, we summarize available in vitro and in vivo data addressing the influence of polymorphisms in drug-metabolizing enzymes on olanzapine serum exposure. The polymorphic CYP2D6 enzyme appears to have no significant influence on olanzapine steady-state serum concentrations. The formation of the various olanzapine metabolites is influenced by polymorphisms in the genes coding for CYP1A2, CYP1A expression regulator AHR, UGT1A4 and UGT2B10, as well as FMO3. An impact on steady-state olanzapine serum concentrations has been suggested for variants of CYP1A2 and UGT1A4, with somewhat conflicting findings. The potential involvement of FMO1 and CYP3A43 in olanzapine disposition has also been suggested but needs future validation.

  17. Moral and policy issues in long-acting contraception.

    Science.gov (United States)

    Brown, G F; Moskowitz, E H

    1997-01-01

    The advent of reversible long-acting contraceptives-IUDs, injectables and implants-has provided women throughout the world with valuable new fertility regulation options. These highly effective methods, together with male and female sterilization, have proven to be enormously popular and are now used by the majority of women and men who are currently contracepting worldwide. Despite their remarkable popularity, long-acting contraceptives have engendered considerable controversy. Political, ethical, and safety questions have emerged, stemming from the ways in which these contraceptives have been developed and used over the course of this century. At the heart of the concern is the issue of reproductive rights and freedom. This paper reviews the history of the development of long-acting contraceptives, including the prospect of new methods that will likely emerge from ongoing research and development. It also examines the history, in the United States and in developing countries, of the use and abuse of long-acting methods, including sterilization, in the context of eugenics and population control policies. It then describes a new paradigm of reproductive health and rights that has emerged from the International Conference on Population Development in Cairo, and which offers an enlightened approach to future policies and programs. In light of the wide variety of ways in which long-acting contraceptives have been provided, the paper examines the rights and responsibilities of governments, family planning providers, and individuals. An ethical framework for the use of long-acting methods is discussed, and public policies for the future are proposed.

  18. Long-acting reversible hormonal contraception

    African Journals Online (AJOL)

    Despite the advantages of long-acting reversible hormonal contraceptive methods, they are ... common; 9% of women used the pill in 2015, 8% relied on male condoms .... contraception for adolescents and young adults: patient and provider.

  19. Focus on olanzapine.

    Science.gov (United States)

    Green, B

    1999-01-01

    Olanzapine (2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5] benzodiazepine) is a novel antipsychotic agent of the theinobenzodiazepine class developed by Eli Lilly & Co. It has a pleotrophic pharmacology and affects the dopaminergic, serotonergic, muscarinic and adrenergic systems. The therapeutic advantage of recent antipsychotics (so-called atypical antipsychotics) has been attributed to additional serotonergic effects. Clinical studies and trials suggest that olanzapine is comparable or superior to haloperidol and may be superior to risperidone in terms of efficacy and side-effect profiles. The starting dose of olanzapine is a single dose of 10 mg. The drug reaches peak plasma levels in 5-8 h, and has a half-life of about 35 h, depending on metabolism. The recommended maximum dose is 20 mg daily, but higher doses have been employed. Abnormalities of the QTc interval on ECG are unlikely to occur and so there is no need for a baseline ECG as with sertindole, which has recently been withdrawn. The most common side-effects are somnolence and weight gain. About 40% of patients in clinical trials gain weight--especially if they are on a high starting dose and if they were underweight pre-treatment. Reported evidence to date suggests that olanzapine is relatively less likely to produce sexual dysfunction. In general, weight gain and sexual dysfunction are of great concern to people taking antipsychotics and the side-effect profile of any antipsychotic may affect compliance. Olanzapine's general efficacy and side-effect profile suggest that, unforeseen post-marketing complications notwithstanding, olanzapine deserves a major place in the first-line management of psychotic disorders.

  20. Rise in RBC aggregability and concomitant decrease in blood pressure 10 days after injection of the long acting erythropoietin analogue methoxy polyethylene glycol-epoetin-β (MIRCERA®).

    Science.gov (United States)

    Joré, Céline; Brun, Jean-Frédéric; Varlet-Marie, Emmanuelle

    2016-01-01

    Erythropoietin (EPO) is a major regulator of blood viscosity. Its long lasting action analogue methoxy polyethylene glycol-epoetin-β (MIRCERA®) seems to be also employed in modern doping. We took the opportunity of a study aiming at developing a detection of recent MIRCERATM injection in the context of doping detection to assess the effects of this EPO analogue on red blood cells (RBC) aggregation. A single dose 200 μg of MIRCERA® was injected to 10 male volunteers and blood samplings were drawn over 24 days. After injection a decrease in mean corpuscular volume at day 2 (p decrease in ferritin a day 5 (p decreased at day 4 (p decrease in systolic blood pressure was observed during the period from day 4 to day 17 (at day 10: -11.90±2.28 mmHg, p decrease in diastolic blood pressure, mean and pulse pressure. Correlations between this decrease in blood pressure and "M" did not reach significance but pulse pressure was positively correlated to "M" (r = 0.743, p decrease in blood pressure, but a possible causative link between the two events is not clearly evidenced.

  1. Glucagon receptor knockout mice are protected against acute olanzapine-induced hyperglycemia.

    Science.gov (United States)

    Castellani, Laura N; Peppler, Willem T; Sutton, Charles D; Whitfield, Jamie; Charron, Maureen J; Wright, David C

    2017-08-01

    To determine if glucagon is involved in mediating the increase in blood glucose levels caused by the second-generation antipsychotic drug olanzapine. Whole body glucagon receptor deficient mice (Gcgr(-/-)) or WT littermate controls were injected with olanzapine (5mg/kg BW IP) and changes in blood glucose measured over the following 120min. Separate cohorts of mice were treated with olanzapine and changes in pyruvate tolerance, insulin tolerance and whole body substrate oxidation were determined. Olanzapine treatment increased serum glucagon and lead to rapid increases in blood glucose concentrations in WT mice. Gcgr(-/-) mice were protected against olanzapine-induced increases in blood glucose but this was not explained by differences in terminal serum insulin concentrations, enhanced AKT phosphorylation in skeletal muscle, adipose tissue or liver or differences in RER. In both genotypes olanzapine induced an equivalent degree of insulin resistance as measured using an insulin tolerance test. Olanzapine treatment led to an exaggerated glucose response to a pyruvate challenge in WT but not Gcgr(-/-) mice and this was paralleled by reductions in the protein content of PEPCK and G6Pase in livers from Gcgr(-/-) mice. Gcgr(-/-) mice are protected against olanzapine-induced increases in blood glucose. This is likely a result of reductions in liver glucose output, perhaps secondary to decreases in PEPCK and G6Pase protein content. Our findings highlight the central role of the liver in mediating olanzapine-induced disturbances in glucose homeostasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. A Case of Olanzapine-Induced Fever

    Science.gov (United States)

    Yang, Cho-Hsiang; Chen, Ying-Yeh

    2017-01-01

    Olanzapine, a frequently used second-generation antipsychotic, has rarely been implicated as a cause of drug-induced fever in the absence of neuroleptic malignant syndrome. We describe a patient who developed isolated fever following olanzapine monotherapy, which subsided after discontinuation of olanzapine. Blockade of dopaminergic receptors and elevated cytokines concentration are possible mechanisms of fever development during treatment with olanzapine. This case calls for attention to olanzapine-induced fever in clinical practice. PMID:28138204

  3. Efficacy of the new long-acting formulation of lanreotide (lanreotide Autogel) in the management of acromegaly.

    OpenAIRE

    Caron, Ph; Beckers,Albert; Cullen, C R; Goth, M. I.; Gutt, B.; Laurberg, P.; Pico, A. M.; VALIMAKI, M; Zgliczynski, W.

    2002-01-01

    Lanreotide Autogel is a new long-acting aqueous preparation of lanreotide for the treatment of acromegaly and is administered by deep sc injection from a small volume, prefilled syringe. The aim of this study was to evaluate the efficacy and safety of this new long-acting formulation in a large population of acromegalic patients previously responsive to lanreotide 30 mg, im (sustained release microparticle formulation). Lanreotide Autogel was administered by deep sc injection every 28 d to 10...

  4. 注射用利培酮微球与非经典抗精神病药治疗精神分裂症的对照研究%A comparative study between long-acting risperidone microsphere injection for treatment of patients with schizophrenia

    Institute of Scientific and Technical Information of China (English)

    谷德康; 杨楠; 白录东

    2010-01-01

    Objective To investigate clinical efficacy and side effects of long-acting risperidone microsphere injection for treatment of patients with schizophrenia. Methods A total of 82 patients with schizophrenia were randomly divided into two groups,study group with long-acting risperidone microsphere injection and control group with atypical antipsychotics treatment for 24 weeks. The Positive and Negative Syndrome Scale (PANSS),The Personal and Social Performance (PSP) and Treatment Emergent Symptoms Scale (TESS) were used to evaluate efficacy and adverse effects of treatment at the end of 1st ,2nd,4th, 12nd and 24th week. Results The therapeutic efficacy in control group was similar to that in study group,and there was no significant difference between the two groups (P> 0.05 ). But the therapeutic efficacy in study group was better than that in control group at the end of the 4nd week (P<0.05 ) , and study group was more likely to improve social function(P < 0. 05 ). Incidence of adverse effects in study group was lower than that in control group , but the difference was not significant (P >0.05 ). The incidence of akathisia symptom in study group was higher than that in control group,but the difference was not significant (P>0.05). The incidence of drowsiness symptom in study group was significantly lower than that in control group(P<0.05 ). Conclusion Long-acting risperidone microsphere injection is as effective as atypical antipsychotics for treatment of patients with schizophrenia, but it has better efficacy in improving social function of the schizophrenia with lower side effects.%目的 探讨注射用利培酮微球治疗精神分裂症的疗效和安全性.方法 符合诊断标准的82名精神分裂症患者分成2组,分别给予注射用利培酮微球和非经典抗精神病药物利培酮、喹硫平、奥氮平治疗24周.于治疗前及治疗后2,4,12,24周末分别采用阳性与阴性症状量表(PANSS)、个体和社会功能量表(PSP)

  5. Olanzapine-induced eosinophilic pleuritis

    Directory of Open Access Journals (Sweden)

    Matthew Evison

    2015-01-01

    Eosinophilic pleural fluid is not a marker of non-malignant aetiology and eosinophilic pleural effusions require a careful and systematic diagnostic work-up. This is the second case report to identify olanzapine as a causative agent in eosinophilic pleural effusion.

  6. Neuroanatomical substrates of the disruptive effect of olanzapine on rat maternal behavior as revealed by c-Fos immunoreactivity

    OpenAIRE

    Zhao, Changjiu; Li, Ming

    2012-01-01

    Olanzapine is one of the most widely prescribed atypical antipsychotic drugs in the treatment of schizophrenia. Besides its well-known side effect on weight gain, it may also impair human parental behavior. In this study, we took a preclinical approach to examine the behavioral effects of olanzapine on rat maternal behavior and investigated the associated neural basis using the c-Fos immunohistochemistry. On postpartum Days 6–8, Sprague-Dawley mother rats were given a single injection of ster...

  7. Olanzapine induced neuroleptic malignant syndrome.

    Science.gov (United States)

    Patra, Bichitra Nanda; Khandelwal, Sudhir K; Sood, Mamta

    2013-01-01

    An 18 year old male diagnosed as a case of bipolar affective disorder (BPAD), developed neuroleptic malignant syndrome (NMS) following treatment with olanzapine (20 mg per day), an atypical antipsychotic drug. NMS is usually seen with typical antipsychotic drugs. The patient was diagnosed as a case of NMS, offending agent was immediately withdrawn and prompt treatment with bromocriptine and levodopa produced a good recovery. The various features of the case are discussed in view of the potential mortality of the syndrome.

  8. Pharmacokinetics of oxytetracycline in goats: modifications induced by a long-acting formulation.

    Science.gov (United States)

    Escudero, E; Carceles, C M; Serrano, J M

    1994-12-03

    The pharmacokinetics of oxytetracycline were studied in goats, after the intravenous and intramuscular injection of a conventional and long-acting formulation. The antibiotic was distributed according to an open two-compartment model. The apparent volume of distribution (Vz) and the central compartment volume (Vc) were 1.443 litres/kg and 0.453 litre/kg, respectively, and the total body clearance was 0.156 litre/kg/hour. The mean half-lives (T1/2 lambda z) of the conventional formulation after intravenous and intramuscular administration were six hours 28 minutes and 10 hours 38 minutes, respectively, whereas the long-acting formulation had half-lives of six hours 36 seconds and 29 hours, respectively, after intravenous and intramuscular injection. From the results of these single administrations two intramuscular dosage regimens can be proposed that achieve minimum concentrations of over 0.5 mg/litre (the minimum inhibitory concentration for most susceptible pathogens): with the conventional formulation by administering an initial dose of 10 mg/kg and a maintenance dose of 8.5 mg/kg every 24 hours, and with the long-acting formulation by administering an initial dose of 20 mg/kg and a maintenance dose of 14 mg/kg every 48 hours.

  9. A suspected case of olanzapine induced hyponatremia

    Directory of Open Access Journals (Sweden)

    Ajay Kumar Bakhla

    2014-01-01

    Full Text Available Here we report a case of a 63-year-old male diagnosed with recurrent depressive disorder and current episode of severe depression with psychotic symptoms, developed hyponatremia soon after addition of olanzapine and increasing the dose of escitalopram. A possible causality association was established with olanzapine, and the possible etiological reasons of this clinically significant risk were discussed.

  10. Clinical blood chemistry values and long acting phenothiazines.

    Science.gov (United States)

    Schneider, S J; Kirby, E J; Itil, T M

    1981-05-01

    Fifty-nine chronic schizophrenic patients received one year of treatment with either fluphenazine enanthate or pipothiazine palmitate IM. Both long acting neuroleptics significantly decreased serum albumin, total protein and creatinine values. Triglycerides were decreased only early in treatment. Pretreatment findings from therapy responders, as compared with those who failed to respond to treatment, included higher albumin values and to a lesser extent, lower lactic dehydrogenase values and greater height. These results were discussed with an eye toward the hepatocellular effects of long acting phenothiazines and the effect of liver function on the pharmacokinetics of these medications.

  11. Olanzapine induced neuroleptic malignant syndrome

    Directory of Open Access Journals (Sweden)

    Bichitra Nanda Patra

    2013-01-01

    Full Text Available An 18 year old male diagnosed as a case of bipolar affective disorder (BPAD, developed neuroleptic malignant syndrome (NMS following treatment with olanzapine (20 mg per day, an atypical antipsychotic drug. NMS is usually seen with typical antipsychotic drugs. The patient was diagnosed as a case of NMS, offending agent was immediately withdrawn and prompt treatment with bromocriptine and levodopa produced a good recovery. The various features of the case are discussed in view of the potential mortality of the syndrome.

  12. Uptake of long-acting reversible contraceptive devices in Western ...

    African Journals Online (AJOL)

    2015-07-01

    Jul 1, 2015 ... The use of long acting reversible methods (LARC) is proposed as a ... administered questionnaire which included information on ... The chance of pregnancy over a year of use is significant- ... gets for maternal health: to reduce maternal mortality .... interval between their last two children less than two years ...

  13. Olanzapine-induced ischemic colitis

    Directory of Open Access Journals (Sweden)

    Esteban Sáez-González

    Full Text Available Background: Ischemic colitis (IC is an uncommon adverse event associated with antipsychotic agents, more commonly found with phenothiazine drugs and atypical neuroleptics such as clozapine. The risk of developing ischemic colitis increases when anticholinergic drugs are associated. Case report: We report the case of a 38-year-old woman with a history of schizoaffective disorder who had been on chronic quetiapine for 3 years, and presented to the ER because of diarrhea for 5 days. Four months previously, olanzapine had been added to her psychiatric drug regimen. Physical examination revealed abdominal distension with abdominal tympanic sounds and tenderness. Emergency laboratory tests were notable for increased acute phase reagents. Tomography revealed a concentric thickening of the colonic wall in the transverse, descending and sigmoid segments, with no signs of intestinal perforation. Colonoscopy demonstrated severe mucosal involvement from the sigmoid to the hepatic flexure, with ulcerations and fibrinoid exudate. Biopsies confirmed the diagnosis of ischemic colitis. The only relevant finding in her history was the newly added drug to her baseline regimen. An adverse effect was suspected because of its anticholinergic action at the intestinal level, and the drug was withdrawn. After 6 months of follow-up clinical, laboratory and endoscopic recovery was achieved. Discussion: Antipsychotic medication should be considered as a potential cause of ischemic colitis, particularly atypical antipsychotics such as clozapine and olanzapine; despite being uncommon, this adverse event may result in high morbidity and mortality.

  14. Eosinophilic myocarditis during treatment with olanzapine

    DEFF Research Database (Denmark)

    Vang, Torkel; Rosenzweig, Mary; Bruhn, Christina Hedegaard

    2016-01-01

    -mortem toxicological examination demonstrated presence of olanzapine, morphine, venlafaxine and oxazepam. Syringes indicating substance abuse were found in his home. Case 2 was a 36-year-old Caucasian man diagnosed with schizophrenia was found dead unexpectedly. There was no history of substance abuse. Current...... fatal cases of eosinophilic myocarditis associated with the use of olanzapine. CASE PRESENTATION: Case 1 was a 39-year-old Caucasian man with known substance abuse and schizophrenia. He was found dead in his home. Olanzapine was prescribed at day -54, and dose at time of death was 40 mg/day. Post...

  15. Bronchodilator treatment of stable COPD: long-acting anticholinergics

    Directory of Open Access Journals (Sweden)

    W. Vincken

    2005-09-01

    Full Text Available Since airflow obstruction in chronic obstructive pulmonary disease (COPD is to some extent reversible, bronchodilators play an important role in the maintenance treatment of COPD the more they reduce hyperinflation and, as a result, improve dyspnoea and exercise capacity. Since parasympathetic activity is the dominant reversible component of airflow obstruction in COPD, inhaled short-acting anticholinergic agents (SAAC, in particular ipratropium, became an efficient and safe first-line treatment, especially when combined with a short-acting beta2-adrenergic receptor agonist. Even better results were obtained when combining the SAAC ipratropium to a long-acting beta2-adrenergic receptor agonist (LABA, once they became available. Recently, tiotropium bromide, the first of a new class of selective and long-acting anticholinergic agents was introduced for once-daily maintenance treatment of COPD patients. Several large long-term randomised clinical trials comparing tiotropium to placebo as well as to the SAAC ipratropium and the LABA salmeterol, have confirmed the long-acting and superior bronchodilator effect of tiotropium without any evidence of drug tolerance developing. These studies also have clearly demonstrated that tiotropium positively affects several other important health outcomes, such as dyspnoea sensation, exercise capacity, utilisation of rescue bronchodilators, health-related quality of life, COPD exacerbations and hospitalisations because of exacerbations. The improvement in these real-life outcomes appears related to the reduction in both static and dynamic hyperinflation. In all these studies, tiotropium was well tolerated and safe; the only relevant side-effect encountered being dry mouth, usually mild and often transitory. Finally, it has been shown that the combination of tiotropium with a LABA affords superior bronchodilatation than both agents alone, indicating that both classes of long-acting bronchodilators should be

  16. Olanzapine-induced tardive oculogyric crises

    Directory of Open Access Journals (Sweden)

    Amar D Bavle

    2013-01-01

    Full Text Available Tardive syndromes are much lower in prevalence in second generation antipsychotics (SGA than in the typical antipsychotics. Although, olanzapine, which is an SGA, has a high risk of causing weight gain, metabolic syndrome, raised blood sugar, and dyslipidemias; it is widely used as the risk of developing extrapyramidal syndromes (EPS is low. Among the various forms of EPS, tardive syndromes are the most feared, tardive dyskinesia, tardive akathisia, and tardive dystonia are the commonest tardive syndromes, the others being less common. Tardive oculogyric crises (TOC are a rare form of tardive dystonia. This patient had TOC with prolonged unsupervised treatment with low-dose olanzapine. Added to that, she developed weight gain that was alarmingly high and such high gain in weight with olanzapine, to our knowledge, has not been reported. She responded to a low dose of trihexiphenydyl, and on stopping olanzapine and adding aripiprazole, has started losing weight.

  17. Eosinophilic myocarditis during treatment with olanzapine

    DEFF Research Database (Denmark)

    Vang, Torkel; Rosenzweig, Mary; Bruhn, Christina Hedegaard;

    2016-01-01

    BACKGROUND: Drug-induced eosinophilic myocarditis is a life-threatening and frequently overlooked condition. The prevalence of myocarditis in clozapine-treated patients may be as high as 3 %. An association between olanzapine and myocarditis has not previously been described, but given the chemical...... fatal cases of eosinophilic myocarditis associated with the use of olanzapine. CASE PRESENTATION: Case 1 was a 39-year-old Caucasian man with known substance abuse and schizophrenia. He was found dead in his home. Olanzapine was prescribed at day -54, and dose at time of death was 40 mg/day. Post......-mortem toxicological examination demonstrated presence of olanzapine, morphine, venlafaxine and oxazepam. Syringes indicating substance abuse were found in his home. Case 2 was a 36-year-old Caucasian man diagnosed with schizophrenia was found dead unexpectedly. There was no history of substance abuse. Current...

  18. Costi ed effetti di Risperidone Long Acting (RLA rispetto ad antipsicotici atipici nel trattamento dei soggetti schizofrenici in Italia

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    Lorenzo G. Mantovani

    2004-03-01

    Full Text Available Objective: to estimate the costs and effects of long-acting risperidone (LAR in the treatment of schizophrenic patients in Italy, as compared to conventional and oral atypical antipsychotics. Methods: a discrete event model was used. The model simulates patients. history for every single therapeutic alternative and selects incident events, on the basis of pre-defined probability distribution-powered, randomized repetitions. The model operates on two types of parameters: patient characteristics and time-dependent variables. Patient characteristics (age, sex, illness profile and severity, probability of incurring in an adverse event and potential dangerousness remain fixed during the 5 simulated years. Time-dependent variables are subject to changes and include outpatient visits, severity of psychotic episodes, symptom-scores, compliance, incidence of adverse effects, site of treatment and dangerousness. Three treatments have been selected: scenario 1 begins with LAR, switches to olanzapine and then to clozapine; scenario 2 starts with olanzapine, switches to oral risperidone and ends with clozapine. Direct medical costs have been computed on the basis of psychiatric visits, drug costs and costs of the institution in which the patient is treated (hospital, rehabilitation clinic, etc. Outcome measures were number of psychotic episodes in 5 years, total time spent during these episodes and cumulative score of positive and negative symptoms at 5 years. Information on alternatives, transition probabilities, model structure and health resources utilization were derived from the literature and from a panel of experts. Results: it has been estimated that LAR is economically dominant (more effective at lower cost respect to oral atypical antipsychotics, being able to prevent 0.87 psychotic episodes per patient, with a net cost saving of 4,773 euro per patient. Sub-group analysis indicate that LAR is always more effective than the considered alternatives

  19. Disposition kinetics of long acting moxifloxacin following intravenous administration in Sheep

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    Chirag M. Modi

    Full Text Available Aim: The objective of the present study was to study the disposition kinetics and dosage regimens of long acting moxifloxacin following intravenous administration at the dose rate of 7.5 mg/kg-1 b. wt. in six male sheep and to calculate dosage regimens of the same in sheep. Materials and Methods: The study was conducted using six healthy male sheep. Long acting Moxifloxacin solution (10 % moxifloxacin in solution with L- arginine, N-butyl alcohol and benzyl alcohol was injected in jugular vein and periodical blood samples were collected from contra-lateral jugular vein in test tubes containing 30-50 IU heparin (anticoagulant at 0.083 (5 min, 0.166 (10 min, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 60, 72 and up to 96 h post administration of drug. Drug concentration in plasma was determined using High Performance Liquid Chromatography (HPLC with Fluorescence Detector. The blood concentrations versus time data were analyzed using software. Results: After single dose intravenous administration of long acting moxifloxacin the plasma concentration of 0.016 ± 0.001 μg/ml-1 was maintained for up to 72 h. Distribution half-life (t and elimination half-life (t were 1.637 ± 0.053 h, and 1/2 1/2 12.130 ± 0.202 h, following IV administration. The mean values of apparent volume of distribution V 5.436 ± 0.135 L/kg-1 d(area as well as mean residence time 10.02 ± 4.787 minute were detected with IV administration. Conclusion: The long acting Moxifloxacin @ the dose 7.5 mg/kg IV maintains the effective therapeutic concentration in the plasma of sheep for up to 72 hours. The long acting Moxifloxacin at this dose rate can be used to treat sensitive bacteria causing infectious diseases in sheep. [Vet World 2012; 5(9.000: 517-521

  20. Olanzapine discontinuation emergent recurrence in bipolar disorder

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    Manu Arora

    2014-01-01

    Full Text Available Objective: The efficacy of atypical antipsychotics including olanzapine in acute treatment of manic episode has been established, whereas its role in maintenance treatment is not clear. Materials and Methods: Thirteen patients of bipolar disorder who were on regular treatment with mood stabilizer and subsequently relapsed into mania or depressive episode after discontinuation of olanzapine were studied for various socio-demographic and clinical factors using retrospective chart review. Results: There was no correlation found between the period of tapering olanzapine, time to recurrence of episode after discontinuation, and the dosage of olanzapine at the time of discontinuation. The predominant early signs of relapse after discontinuation of olanzapine included sleep disturbance (72.7%, lack of insight for change in behavior (72.7%, irritability (54.5%, and elevated mood (45.5%. Conclusion: Mood stabilizer alone as a maintenance therapy of bipolar disorder may be inadequate for long-term management. A low dose of olanzapine along with mood stabilizers might be useful for prevention of recurrence in bipolar disorder.

  1. Insulin degludec is a new ultra-long-acting insulin analogue

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    Ivan Ivanovich Dedov

    2014-06-01

    Full Text Available Achieving optimal glycemic control is an important aspect of preventing and slowing the progression of diabetes-associated complications, and reducing the cost of their treatment. Long-acting insulin analogues, glargine and detemir, provide better metabolic control with reduced risk of hypoglycaemia as compared to NPH insulin. However, fear of hypoglycaemia and weight gain, as well as the complexity of regimen, are still the most important barriers to well-timed initiation and intensification of insulin therapy. Insulin degludec (Tresiba® is a new ultra-long-acting insulin analogue. After subcutaneous injection degludec forms repository of soluble multi-hexamers, which are gradually absorbed to the bloodstream, providing a flat, stable antihyperglycemic effect lasting more than 42 h, and low intra-individual variability as opposed to currently used basal insulin analogues, insulin glargine and insulin detemir. In the seven randomized, open label, controlled phase 3 trials lasting 26 or 52 weeks, using treat-to-target (no more non-inferiority design, insulin degludec provided glycemic control similar to that of insulin glargine with lower risk of nocturnal hypoglycaemia and good safety profile in patients with type 1 or 2 diabetes. Furthermore, trials examining a flexible dosing regimen of insulin degludec in patients with type 1 or 2 diabetes have shown that it is possible to vary the injection time without compromising glycemic control or safety of the therapy.

  2. Olanzapine versus haloperidol: Which can control stuttering better?

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    Vahid Shaygannejad

    2013-01-01

    Conclusions: It seems that olanzapine does have better impact in controlling stuttering, and it may be recommended to prescribe olanzapine for stutters as the first choice to control the stuttering under a careful follow-up.

  3. Short-term treatment with olanzapine does not modulate gut hormone secretion: olanzapine disintegrating versus standard tablets

    DEFF Research Database (Denmark)

    Vidarsdottir, Solrun; Roelfsema, Ferdinand; Streefland, Trea;

    2009-01-01

    BACKGROUND: Treatment with olanzapine (atypical antipsychotic drug) is frequently associated with various metabolic anomalies, including obesity, dyslipidemia, and diabetes mellitus. Recent data suggest that olanzapine orally disintegrating tablets (ODT), which dissolve instantaneously in the mouth...

  4. [Intravenous regional anesthesia with long-acting local anesthetics. An update].

    Science.gov (United States)

    Atanassoff, P G; Lobato, A; Aguilar, J L

    2014-02-01

    Intravenous regional anesthesia is a widely used technique for brief surgical interventions, primarily on the upper limbs and less frequently, on the lower limbs. It began being used at the beginning of the 20th century, when Bier injected procaine as a local anesthetic. The technique to accomplish anesthesia has not changed much since then, although different drugs, particularly long-acting local anesthetics, such as ropivacaine and levobupivacaine in low concentrations, were introduced. Additionally, drugs like opioids, muscle relaxants, paracetamol, neostigmine, magnesium, ketamine, clonidine, and ketorolac, have all been investigated as adjuncts to intravenous regional anesthesia, and were found to be fairly useful in terms of an increased onset of operative anesthesia and longer lasting perioperative analgesia. The present article provides an overview of current knowledge with emphasis on long-acting local anesthetic drugs. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  5. Cognitive effects of olanzapine treatment in schizophrenia.

    Science.gov (United States)

    McGurk, Susan R; Lee, M A; Jayathilake, K; Meltzer, Herbert Y

    2004-05-10

    Improvement in some but not all domains of cognition during treatment with the atypical antipsychotic drugs clozapine, quetiapine, olanzapine, and risperidone has been reported in some but not all studies. It has been recently suggested that these reports are an artifact, related to lessening of the impairment due to typical neuroleptic drugs and anticholinergic agents. The purpose of this study was to further test the hypothesis that olanzapine, an atypical antipsychotic drug reported to have anticholinergic properties, improves cognition in patients with schizophrenia, including domains of cognition related closely to work and social function (ie, verbal learning and memory) and that this improvement is independent of improvement in psychopathology. Thirty-four patients with schizophrenia who were partial responders to typical antipsychotic drug treatment were evaluated with a comprehensive neurocognitive battery, including measures of executive functioning; verbal and visual learning and memory; working memory; immediate, selective, and sustained attention; perceptual/motor processing; and motor skills prior to and following treatment with olanzapine for 6 weeks. The Brief Psychiatric Rating Scale (BPRS) was used to assess psychopathology in patients treated with typical antipsychotic drugs. Subjects were switched to olanzapine (average dose 13.4 mg, range 5-20 mg) and reassessed following 6 weeks and 6 months of treatment. Significant improvement was noted in 9 of 19 cognitive tests, including measures of selective attention, verbal learning and memory, and verbal fluency. No cognitive test was worsened by olanzapine treatment. Improvements in the BPRS Total and Positive Symptom Subscale scores were noted. Improvements in verbal learning and memory, sustained attention, and psychomotor tracking were independent of improvement in psychopathology. These data suggest that olanzapine improved some but not all cognitive deficits in schizophrenia, including verbal

  6. Pharmacokinetics, Pharmacodynamics, and Efficacy of a Novel Long-Acting Human Growth Hormone: Fc Fusion Protein.

    Science.gov (United States)

    Kim, Su Jin; Kwak, Hyun-Hee; Cho, Sung Yoon; Sohn, Young Bae; Park, Sung Won; Huh, Rimm; Kim, Jinsup; Ko, Ah-Ra; Jin, Dong-Kyu

    2015-10-05

    The current recombinant human growth hormone (rhGH) therapy requires daily subcutaneous (sc) injections, which results in poor patient compliance, especially in young children. To reduce the dosing frequency, we generated a chimeric protein of rhGH and the Fc-domain of immunoglobulin G (IgG) (rhGH-Fc). The pharmacokinetics and pharmacodynamics of sc-injected rhGH-Fc were assessed in male Sprague-Dawley rats and hypophysectomized rats, respectively. A single sc injection of rhGH-Fc at a dose of 0.2 mg/kg slowly reached a Cmax of 16.80 ng/mL and remained for 7 days with a half-life of 51.1 h. Conversely, a single sc injection of rhGH 0.2 mg/kg rapidly reached a Cmax of 46.88 ng/mL and declined with a half-life of 0.55 h to baseline values in 4 h. In the efficacy study, the sc-injected rhGH-Fc induced rapid weight gain and tibial width growth at a dose of 240 μg/animal. The effect of two injections of rhGH-Fc separated by 1 week was comparable to that of the same dose of 14 daily injections of rhGH. The rhGH-Fc is a novel candidate for long-acting rhGH therapy with more convenient weekly administration, as it reduces glomerular filtration and receptor-mediated clearance while allowing for the rapid reversal of potential adverse events.

  7. Long-acting GLP-1 analogs for the treatment of type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Vilsbøll, Tina; Knop, Filip K

    2008-01-01

    Type 2 diabetes mellitus is characterized by insulin resistance, impaired glucose-induced insulin secretion, and inappropriately elevated glucagon levels which eventually result in hyperglycemia. The currently available treatment modalities for type 2 diabetes are often unsatisfactory in getting...... for the treatment of type 2 diabetes has become available in the US (since October 2005) and in Europe (since May 2007): the incretin-based therapies. The incretin-based therapies fall into two different classes: (i) incretin mimetics, i.e. injectable peptide preparations with actions similar to the natural...... for the development of glucagon-like peptide-1 (GLP-1) analogs, reviews clinical experience gained so far, and discusses future expectations for long-acting forms of GLP-1 analogs....

  8. Olanzapine-induced neuroleptic malignant syndrome in a patient with bipolar affective disorder: Does quetiapine holds the solution?

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    Praveen Tripathi

    2013-01-01

    Full Text Available Neuroleptic Malignant Syndrome (NMS is a rare, severe and life threatening condition induced by antipsychotic medications. It is commonly encountered with the use of first generation antipsychotics, however cases of NMS have been reported with the use of second generation antipsychotics like Olanzapine, Risperidone, Paliperidone, Aripiprazole, Ziprasidone, Amisulpride, Quetiapine and Clozapine, though the incidence of such reports is rare. Due to decreased use of first generation antipsychotics, NMS is reported less frequently now a days. In this case report- we highlight the management issues of a patient suffering from bipolar affective disorder, who had developed NMS following intramuscular injection of haloperidol, which was withdrawn and olanzapine was given later on. The patient had again developed NMS with olanzapine. Finally the patient was managed with modified electroconvulsive therapy and discharged on Lithium carbonate and Quetiapine.

  9. Massive Levemir (Long-Acting Insulin Overdose: Case Report

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    Mamatha Oduru

    2012-01-01

    Full Text Available A 52-year-old insulin-dependant diabetic man presented to the Emergency Department 2 hours after a deliberate massive overdose of 2100 units of long-acting Levemir insulin and a large quantity of whisky. On initial assessment, his GCS was 3/15 and his capillary blood sugar was 2.6 mmol/L. The patient was given a 50 ml bolus of 50% dextrose, followed by intravenous infusions of both 5% and 10% dextrose. Despite the continuous infusions, he experienced 4 symptomatic hypoglycaemic episodes in the first 12 hours after admission. These were managed with oral glucose, IM glucagon, and further dextrose boluses. Blood electrolytes and pH were monitored throughout. Insulin overdoses are relatively common and often occur with an excess of other drugs or alcohol which can enhance its action. Overdoses can result in persistent hypoglycaemia, liver enzyme derangement, electrolyte abnormalities, and neurological damage. Overall mortality is 2.7% with prognosis poorest in patients who are admitted with decreased Glasgow Coma scale (GCS 12 hours after overdose.

  10. Olanzapine-Induced Hypertriglyceridemia Resulting in Necrotizing Pancreatitis

    Science.gov (United States)

    Roy-Chaudhury, Prabir; Yadlapalli, Ganesh

    2016-01-01

    Olanzapine is an atypical antipsychotic agent that was approved by the Food and Drug Administration in 1996 for treatment of psychotic disorders, bipolar disorder, and schizophrenia. Since that time, numerous case reports have been published that describe the association of olanzapine and the development of pancreatitis. Furthermore, 3 reports suggest the mechanism of olanzapine-induced hypertriglyceridemia as the etiology of this progression. We report a case of a 36-year-old man who developed necrotizing pancreatitis secondary to olanzapine-induced hypertriglyceridemia. This case, to our knowledge, is the most severe case of this progression and the first case requiring plasmapheresis for acute management.

  11. Neuroanatomical substrates of the disruptive effect of olanzapine on rat maternal behavior as revealed by c-Fos immunoreactivity.

    Science.gov (United States)

    Zhao, Changjiu; Li, Ming

    2012-12-01

    Olanzapine is one of the most widely prescribed atypical antipsychotic drugs in the treatment of schizophrenia. Besides its well-known side effect on weight gain, it may also impair human parental behavior. In this study, we took a preclinical approach to examine the behavioral effects of olanzapine on rat maternal behavior and investigated the associated neural basis using the c-Fos immunohistochemistry. On postpartum days 6-8, Sprague-Dawley mother rats were given a single injection of sterile water or olanzapine (1.0, 3.0 or 5.0mg/kg, sc). Maternal behavior was tested 2h later, after which rats were sacrificed and brain tissues were collected. Ten brain regions that were either implicated in the action of antipsychotic drugs and/or in the regulation of maternal behavior were examined for c-Fos immunoreactivity. Acute olanzapine treatment dose-dependently disrupted various components of maternal behavior (e.g., pup retrieval, pup licking, nest building, crouching) and increased c-Fos immunoreactivity in the medial prefrontal cortex (mPFC), nucleus accumbens shell and core (NAs and NAc), dorsolateral striatum (DLSt), ventral lateral septum (LSv), central amygdala (CeA) and ventral tegmental area (VTA), important brain areas generally implicated in the incentive motivation and reward processing. In contrast, olanzapine treatment did not alter c-Fos in the medial preoptic nucleus (MPN), ventral bed nucleus of the stria terminalis (vBST) and medial amygdala (MeA), the core brain areas directly involved in the mediation of rat maternal behavior. These findings suggest that olanzapine disrupts rat maternal behavior primarily by suppressing incentive motivation and reward processing via its action on the mesocorticolimbic dopamine systems, other limbic and striatal areas, but not by disrupting the core processes involved in the mediation of maternal behavior in particular.

  12. Implementing Immediate Postpartum Long-Acting Reversible Contraception Programs.

    Science.gov (United States)

    Hofler, Lisa G; Cordes, Sarah; Cwiak, Carrie A; Goedken, Peggy; Jamieson, Denise J; Kottke, Melissa

    2017-01-01

    To understand the most important steps required to implement immediate postpartum long-acting reversible contraception (LARC) programs in different Georgia hospitals and the barriers to implementing such a program. This was a qualitative study. We interviewed 32 key personnel from 10 Georgia hospitals working to establish immediate postpartum LARC programs. Data were analyzed using directed qualitative content analysis principles. We used the Stages of Implementation to organize participant-identified key steps for immediate postpartum LARC into an implementation guide. We compared this guide to hospitals' implementation experiences. At the completion of the study, LARC was available for immediate postpartum placement at 7 of 10 study hospitals. Participants identified common themes for the implementation experience: team member identification and ongoing communication, payer preparedness challenges, interdependent department-specific tasks, and piloting with continuing improvements. Participants expressed a need for anticipatory guidance throughout the process. Key first steps to immediate postpartum LARC program implementation were identifying project champions, creating an implementation team that included all relevant departments, obtaining financial reassurance, and ensuring hospital administration awareness of the project. Potential barriers included lack of knowledge about immediate postpartum LARC, financial concerns, and competing clinical and administrative priorities. Hospitals that were successful at implementing immediate postpartum LARC programs did so by prioritizing clear communication and multidisciplinary teamwork. Although the implementation guide reflects a comprehensive assessment of the steps to implementing immediate postpartum LARC programs, not all hospitals required every step to succeed. Hospital teams report that implementing immediate postpartum LARC programs involves multiple departments and a number of important steps to consider. A

  13. Pharmacokinetics of a long-acting chloramphenicol formulation administered by intramuscular and subcutaneous routes in cattle.

    Science.gov (United States)

    Sanders, P; Guillot, P; Mourot, D

    1988-06-01

    The pharmacokinetic properties of a long-acting formulation of chloramphenicol were determined in six yearling cattle after a single intravenous (i.v.) administration (40 mg/kg body weight) and after two sequential subcutaneous (s.c.) or intramuscular (i.m.) administrations (90 mg/kg/48 h). The two extravascular routes were studied during a crossover trial for a bioequivalence test. After i.v. administration, the plasma concentration-time graph was characteristic of a two-compartment open model. Mean values were a half-life of 4.1 h, a volume of distribution of 0.86 l/kg and a body clearance of 0.128 l/kg/h. Plasma concentrations of chloramphenicol following i.m. and s.c. administrations increased slowly to a broad peak at 10-15 micrograms/ml between 9 and 12 h. Bioavailability was 19.1% after i.m. injection and 12.4% after s.c. administration. The extent of absorption from the two routes did not differ significantly. The rate of absorption was significantly lower after s.c. application than it was after i.m. injection. The time necessary for the plasma concentration to exceed 5 micrograms/ml was the same for the two routes. Thus, i.m. and s.c. routes are bioequivalent.

  14. A long-acting GH receptor antagonist through fusion to GH binding protein.

    Science.gov (United States)

    Wilkinson, Ian R; Pradhananga, Sarbendra L; Speak, Rowena; Artymiuk, Peter J; Sayers, Jon R; Ross, Richard J

    2016-10-12

    Acromegaly is a human disease of growth hormone (GH) excess with considerable morbidity and increased mortality. Somatostatin analogues are first line medical treatment but the disease remains uncontrolled in up to 40% of patients. GH receptor (GHR) antagonist therapy is more effective but requires frequent high-dose injections. We have developed an alternative technology for generating a long acting potent GHR antagonist through translational fusion of a mutated GH linked to GH binding protein and tested three candidate molecules. All molecules had the amino acid change (G120R), creating a competitive GHR antagonist and we tested the hypothesis that an amino acid change in the GH binding domain (W104A) would increase biological activity. All were antagonists in bioassays. In rats all antagonists had terminal half-lives >20 hours. After subcutaneous administration in rabbits one variant displayed a terminal half-life of 40.5 hours. A single subcutaneous injection of the same variant in rabbits resulted in a 14% fall in IGF-I over 7 days.

  15. Determination of olanzapine and N-desmethyl-olanzapine in plasma using a reversed-phase HPLC coupled with coulochemical detection: correlation of olanzapine or N-desmethyl-olanzapine concentration with metabolic parameters.

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    Mong-Liang Lu

    Full Text Available BACKGROUND: Olanzapine (OLZ is one of the most prescribed atypical antipsychotic drugs but its use is associated with unfavorable metabolic abnormalities. N-desmethyl-olanzapine (DMO, one of the OLZ metabolites by CYP1A2, has been reported to have a normalizing action on metabolic abnormalities, but this remains unclear. Our aim was to explore the correlation between the concentrations of OLZ or DMO with various metabolic parameters in schizophrenic patients. METHODS: The chromatographic analysis was carried out with a solvent delivery system coupled to a Coulochem III coulometric detector to determine OLZ and DMO simultaneously in OLZ-treated patients. The correlation between the concentration of OLZ or DMO and the metabolic parameters was analyzed by the Spearman rank order correlation method (r s. PRINCIPAL FINDINGS: The established analytical method met proper standards for accuracy and reliability and the lower limitation of quantification for each injection of DMO or OLZ was 0.02 ng. The method was successfully used for the analysis of samples from nonsmoking patients (n = 48 treated with OLZ in the dosage range of 5-20 mg per day. There was no correlation between OLZ concentrations and tested metabolic parameters. DMO concentrations were negatively correlated with glucose (r s = -0.45 and DMO concentrations normalized by doses were also negatively correlated with insulin levels (r s = -0.39; however, there was a marginally positive correlation between DMO and homocysteine levels (r s = +0.38. CONCLUSIONS: The observed negative correlations between levels of DMO and glucose or insulin suggest a metabolic normalization role for DMO regardless of its positive correlation with a known cardiovascular risk factor, homocysteine. Additional studies of the mechanisms underlying DMO's metabolic effects are warranted.

  16. Olanzapine-Induced Neuroleptic Malignant Syndrome

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    Seyedhamze Hosseini

    2017-05-01

    Full Text Available Neuroleptic malignant syndrome (NMS is a rare but life-threatening idiosyncratic side effect resulting from neuroleptic drugs. NMS mainly occurs in patients treated with high-potency typical antipsychotics, but rarely caused by atypical antipsychotics. Although NMS is less common with atypical antipsychotic, but it seems that its incidence is rising due to increased administration of such drugs. We present the case of a 27-year-old man with a history of paranoid schizophrenia that showed signs consistent with NMS that occurred after treatment with olanzapine. The patient was adherent to treatment. He had decreased level of consciousness, muscle rigidity, diaphoresis, fever, drooling, urinary incontinence, and high blood pressure. This patient illustrates that NMS can occur due to treatment with atypical antipsychotic drugs like olanzapine, particularly in the presence of risk factors. This phenomenon is often unrecognized, underdiagnosed, or not treated properly. Physicians should be aware that NMS with extrapyramidal syndrome could occur with olanzapine at steady state doses without recent dosage adjustments or titration. It is essential that adequate and safe dose of medication is chosen and the patient is monitored by the signs and symptoms of this lethal syndrome.

  17. Olanzapine versus other atypical antipsychotics for schizophrenia

    Science.gov (United States)

    Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; Duggan, Lorna; Kissling, Werner; Leucht, Stefan

    2014-01-01

    Background In many countries of the industrialised world second generation (“atypical”) antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of olanzapine differs from that of other second generation antipsychotics. Objectives To evaluate the effects of olanzapine compared to other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. Search methods 1. Electronic searching We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. 2. Reference searching We inspected the reference of all identified studies for more trials. 3. Personal contact We contacted the first author of each included study for missing information. 4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. Selection criteria We included all randomised trials that used at least single-blind (rater-blind) design, comparing oral olanzapine with oral forms of amisulpride, aripiprazole, clozapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. Main results The review currently includes 50 studies and 9476 participants which provided data for six comparisons (olanzapine compared to amisulpride, aripiprazole

  18. Corticotropin, Repository Injection

    Science.gov (United States)

    H.P. Acthar Gel® ... Corticotropin repository injection comes as a long acting gel to inject under the skin or into a ... prescription and nonprescription medications, vitamins, nutritional supplements, or herbal products you are taking or plan to take. ...

  19. Treatment with long-acting lanreotide autogel in early infancy in patients with severe neonatal hyperinsulinism.

    Science.gov (United States)

    Corda, Heike; Kummer, Sebastian; Welters, Alena; Teig, Norbert; Klee, Dirk; Mayatepek, Ertan; Meissner, Thomas

    2017-06-02

    Treatment of severe diffuse congenital hyperinsulinism (CHI) without sufficient response to diazoxide is complicated by the lack of approved drugs. Therefore, patients are often hospitalized long-term or have to undergo pancreatic surgery if episodes of severe hypoglycaemia cannot be prevented. A long-acting somatostatin analogue, octreotide, has been reported to be an effective treatment option that prevents severe hypoglycaemia in children with CHI, and its off-label use is common in CHI. However, octreotide requires continuous i.v. or s.c. infusion or multiple daily injections. Here, we report our experiences with the use of a monthly application of a long-acting somatostatin analogue, lanreotide autogel® (LAN-ATG), in early infancy. The mean blood glucose concentration within 7 days before the first LAN-ATG administration were compared to 7 days after the first LAN-ATG administration and increased by 0.75 mmol/L (range 0.39-1.19 mmol/L). In the following weeks intravenous glucose infusions, octreotide, and glucagon treatment could be successfully stopped in all patients 3-20 days after the first LAN-ATG injection without substantial worsening of the hypoglycaemia rate. Increased carbohydrate requirements could be normalized with an average reduction in the carbohydrate-intake of 7 g/kg body weight/d (range 1.75-12.8 g/kg body weight/d). Over a total of 52 treatment months, no serious adverse effects occurred. Long-term LAN-ATG treatment improved blood glucose concentrations, lowered the frequency of hypoglycaemia or allowed for normalization of oral carbohydrate intake in infants with CHI younger than 6 months of age. No severe side effects were observed. LAN-ATG might be an alternative treatment option in infants with severe CHI who lack risk factors for necrotizing enterocolitis and are not responding to current treatment regimens as an alternative to surgery after careful individual evaluation.

  20. Olanzapine affects locomotor activity and meal size in male rats

    NARCIS (Netherlands)

    van der Zwaal, Esther M.; Luijendijk, Mieneke C. M.; Evers, Simon S.; la Fleur, Susanne E.; Adan, Roger A. H.

    2010-01-01

    Olanzapine is an antipsychotic drug that frequently induces weight gain accompanied by increased fat deposition as a side effect To investigate how olanzapine affects different aspects of energy balance we used male rats to determine effects on meal patterns food preference locomotor activity and

  1. Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs

    Directory of Open Access Journals (Sweden)

    Michael Guarnieri

    2014-01-01

    Full Text Available Background: Long-acting therapy in laboratory animals offers advantages over the current practice of 2-3 daily drug injections. Yet little is known about the disintegration of biodegradable drug implants in rodents. Objective: Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets. Methods: Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets. Results: Drug levels are below the level of detection (0.5 ng/mL plasma within 4-5 days of implant. However, necroscopy revealed that interstitial tissues begin to seal implants within a week. Visual inspection of the implant site revealed no evidence of inflammation or edema associated with the cholesterol-drug residue. Chemical analyses demonstrated that the residues contained 10-13% of the initial opiate dose for at least two weeks post implant. Discussion: The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space. Conclusion: Drug implants can retain significant and unintended reservoirs of drugs.

  2. Young women's attitudes towards, and experiences of, long-acting reversible contraceptives.

    Science.gov (United States)

    Bracken, Jennifer; Graham, Cynthia A

    2014-08-01

    To identify factors involved in women's decisions to choose particular contraceptive methods and more specifically, incentives and disincentives to use three long-acting reversible contraceptive (LARC) methods: injectables, implants, and intrauterine devices/systems (IUDs/IUSs). A total of 502 women aged 18 to 30 completed a cross-sectional online questionnaire. The three most important factors in choosing a contraceptive method were: high efficacy at preventing pregnancy, protection against sexually transmitted infections, and non-interference with sexual intercourse. The most common incentives for LARC use were the high efficacy and long duration of action. Disincentives included the possibility of irregular bleeding and concerns about effects on fertility; fear of needles and pain was a particular disincentive for IUD/IUS use. Only 93 (18%) of the participants reported ever having used a LARC. Reported disincentives to LARC use (e.g., concern about effects on future fertility) indicated that many young women hold inaccurate beliefs about these methods. The relatively high proportions of women who held neutral attitudes about LARCs (21-40%, depending on the method) highlight the importance of education and contraceptive counselling to improve knowledge about the advantages of these methods.

  3. Long-acting neuroleptics used in wildlife management do not impair thermoregulation or physical activity in goats (Capra hircus).

    Science.gov (United States)

    Fick, Linda; Mitchell, Duncan; Fuller, Andrea

    2007-06-01

    Long-acting neuroleptics commonly are used in wildlife management to decrease stress-related mortality in wild animals, but with possible effects on thermoregulation, which may contribute to residual morbidity and mortality. We investigated the effects of haloperidol (0.01, 0.1, 1 mg kg(-1), n=4), zuclopenthixol (0.1, 1, 10 mg kg(-1), n=4) and perphenazine (0.1, 1, 10 mg kg(-1), n=8), as well as control injections of sunflower oil, on body temperature and physical activity of laboratory goats under hot, cold and thermoneutral ambient temperatures. Implanted data loggers continuously recorded abdominal temperature, and data loggers attached externally on the foreleg recorded movement of unrestrained goats, in a climatic chamber at 35 degrees C, 10 degrees C and 22 degrees C. Cycling ambient temperature between 35 degrees C in daytime and 10 degrees C at night time caused a significant increase in amplitude of the circadian rhythm of body temperature in goats given sunflower oil (P=0.0012, unpaired t-test, n=8), but the administration of zuclopenthixol or perphenazine did not affect this change in amplitude (P>0.05, two-way ANOVA, n=4). Mean daily body temperature after administration of zuclopenthixol or perphenazine, and mean daily activity after zuclopenthixol administration, were not significantly different to those after control injections, at any ambient temperature, for the expected duration of drug activity (all P>0.05, two-way ANOVA, n=4). Thermal response indices, and mean activity, during heat, cold or thermoneutral exposure, of goats for 7 h after haloperidol injection, were not significantly different, at any dose or any ambient temperature, to those following control injections (all P>0.05, repeated measures ANOVA, n=4). Long-acting neuroleptics did not impair activity or thermoregulation of goats subjected to inescapable thermal challenges.

  4. Immunosuppressant-Associated Neurotoxicity Responding to Olanzapine

    Directory of Open Access Journals (Sweden)

    James A. Bourgeois

    2014-01-01

    Full Text Available Immunosuppressants, particularly tacrolimus, can induce neurotoxicity in solid organ transplantation cases. A lower clinical threshold to switch from tacrolimus to another immunosuppressant agent has been a common approach to reverse this neurotoxicity. However, immunosuppressant switch may place the graft at risk, and, in some cases, continuation of the same treatment protocol may be necessary. We report a case of immunosuppressant-associated neurotoxicity with prominent neuropsychiatric manifestation and describe psychiatric intervention with olanzapine that led to clinical improvement while continuing tacrolimus maintenance.

  5. Long-acting reversible contraceptive acceptability and unintended pregnancy among women presenting for short-acting methods: a randomized patient preference trial.

    Science.gov (United States)

    Hubacher, David; Spector, Hannah; Monteith, Charles; Chen, Pai-Lien; Hart, Catherine

    2017-02-01

    Measures of contraceptive effectiveness combine technology and user-related factors. Observational studies show higher effectiveness of long-acting reversible contraception compared with short-acting reversible contraception. Women who choose long-acting reversible contraception may differ in key ways from women who choose short-acting reversible contraception, and it may be these differences that are responsible for the high effectiveness of long-acting reversible contraception. Wider use of long-acting reversible contraception is recommended, but scientific evidence of acceptability and successful use is lacking in a population that typically opts for short-acting methods. The objective of the study was to reduce bias in measuring contraceptive effectiveness and better isolate the independent role that long-acting reversible contraception has in preventing unintended pregnancy relative to short-acting reversible contraception. We conducted a partially randomized patient preference trial and recruited women aged 18-29 years who were seeking a short-acting method (pills or injectable). Participants who agreed to randomization were assigned to 1 of 2 categories: long-acting reversible contraception or short-acting reversible contraception. Women who declined randomization but agreed to follow-up in the observational cohort chose their preferred method. Under randomization, participants chose a specific method in the category and received it for free, whereas participants in the preference cohort paid for the contraception in their usual fashion. Participants were followed up prospectively to measure primary outcomes of method continuation and unintended pregnancy at 12 months. Kaplan-Meier techniques were used to estimate method continuation probabilities. Intent-to-treat principles were applied after method initiation for comparing incidence of unintended pregnancy. We also measured acceptability in terms of level of happiness with the products. Of the 916

  6. Long-acting beta(2)-agonists in management of childhood asthma

    DEFF Research Database (Denmark)

    Bisgaard, H

    2000-01-01

    This review assesses the evidence regarding the use of long-acting beta(2)-agonists in the management of pediatric asthma. Thirty double-blind, randomized, controlled trials on the effects of formoterol and salmeterol on lung function in asthmatic children were identified. Single doses of inhaled......, long-acting beta(2)-agonists provide effective bronchodilatation and bronchoprotection when used as intermittent, single-dose treatment of asthma in children, but not when used as regular treatment. Future studies should examine the positioning of long-acting beta(2)-agonists as an "as needed" rescue...... medication instead of short-acting beta(2)-agonists for pediatric asthma management....

  7. Naturalistic study of olanzapine in treatment-resistaant ...

    African Journals Online (AJOL)

    Naturalistic study of olanzapine in treatment-resistaant schizophrenia and acute mania, depression and obsessional disorder. ... depression, four obsessive compulsive disorder (OCD), one each had schizo-affective and delusional disorders, ...

  8. Depletion of long-acting ampicillin in goat milk following intramuscular administration.

    Science.gov (United States)

    Ferrini, Anna Maria; Trenta, Simona; Mannoni, Veruscka; Rosati, Remo; Coni, Ettore

    2010-12-08

    Although goat milk production represents today a very small percentage of the world milk market, this percentage has been growing continuously during the past 20 years. Goat milk is the basic milk supply in many developing countries and provides tasteful derivative products in developed countries. Goats, as well as all milk-producing animals, can be affected by mastitis, but goats being considered a minor species, few drugs are specifically registered for these animals; most, at least for mastitis treatment, are usually tested and registered for use in cows. This situation leads often to the adoption for goat milk of withdrawal periods defined for cows even if these extrapolations prove almost never valid for goats. In the present study, the elimination of the β-lactam antibacterial agent ampicillin in goat milk was investigated. Ampicillin was chosen because it is one of the most common antibiotics used by goat farmers against mastitis due to the fact that it is well tolerated and has short elimination times in cows. Goats were treated with long-acting ampicillin at 15 mg (kg of body weight)(-1) by double intramuscular injection at 72 h interval. Milk was collected in a 12 h milking scheme. The method used to determine the levels of ampicillin in goat milk was based on a liquid-liquid extraction of this drug from the matrix, successive derivatization with formaldehyde, and final separation by HPLC with fluorescence detection. The results point out a slow depletion of ampicillin and, consequently, a withdrawal period (13 milkings) longer than that extrapolated and authorized for cows and sheep.

  9. Medroxyprogesterone acetate or long-acting progesterone in the biostimulation of lambs

    Directory of Open Access Journals (Sweden)

    Luis C.O. Magalhães

    2010-09-01

    Full Text Available The aim of this study was to evaluate the response of prepubertal ewe lambs to exogenous administration of either medroxyprogesterone acetate (MAP or long-acting progesterone (LAP together with biostimulation. Two Pool Dorset adult males and 75 mixed-breed prepubertal ewe lambs (average of 179 days-old and 30.0kg were used. The females were randomly assigned to three different groups. In the first group the females were submitted to the insertion of intravaginal sponges containing MAP (60 mg for 12 days and were then biostimulated for eight weeks. In the second group the females were submitted to a single injection of LAP (225 mg and then to biostimulation for eight weeks. In the last group, the females were only submitted to biostimulation for eight weeks. Animals were considered cyclic when plasma progesterone (P4 concentration exceeded 1.0 ng/mL in at least one of two consecutive blood samples taken within a 7-day interval in three distinct experimental moments. After treatments 93.3% of the females disregarding their group started their cyclicity and most of them (92.0%, continued to be cyclic after 63 days of either MAP or LAP together with biostimulation under both male and female effect. We conclude that prepubertal ewe lambs when submitted to protocols of either MAP or LAP followed by biostimulation result in puberty at the 7 month of age. It can be deducted that some ewe lambs submitted to the administration of either MAP or LAP together with biostimulation promoted a multiplier effect upon the other young females that were then stimulated to start cyclicity.

  10. Pediatricians' Attitudes and Beliefs about Long-Acting Reversible Contraceptives Influence Counseling.

    Science.gov (United States)

    Berlan, Elise D; Pritt, Nicole M; Norris, Alison H

    2017-02-01

    Adolescents are at high risk for unintended pregnancy. Because of pediatricians' potential role in contraceptive counseling, understanding their attitudes and beliefs and counseling practices about use of long-acting reversible contraceptives (LARC; ie, etonogestrel implant and intrauterine devices [IUDs]) is vital. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We interviewed primary care pediatricians (N = 23) in a Midwestern city in June-August 2014. We transcribed the interviews, developed a coding schema, and analyzed these qualitative data using a priori and open coding of transcripts. Few pediatricians had favorable views on adolescent IUD use and most did not include IUDs in routine contraception counseling. Pediatricians perceived IUDs to impose significant risks for adverse reproductive outcomes and to be poorly tolerated by adolescents. Poor and/or outdated knowledge influenced inaccurate beliefs and unsupportive attitudes. Whereas some pediatricians were advocates for adolescent use of IUDs, many others had concerns that IUDs were not appropriate and not favored by adolescents. In contrast, participants viewed the etonogestrel implant more favorably and often included it in routine counseling. Some pediatricians focused on the familiar and readily available methods (injectable and oral contraceptives) or assumed patients had predetermined expectations for those methods. Time spent counseling on LARC was also perceived as a barrier. Pediatricians described how education and increased familiarity with LARC changed viewpoints. A variety of beliefs and attitudes, as well as factors such as time and personal habits, influence pediatricians' contraceptive counseling practices. Until knowledge deficits are addressed, uninformed viewpoints and unfavorable attitudes will limit adolescents' access to LARC, especially IUDs. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All

  11. [Olanzapine improves chorea in patients with Huntington's disease].

    Science.gov (United States)

    Jiménez-Jiménez, F J; de Toledo, M; Puertas, I; Barón, M; Zurdo, M; Barcenilla, B

    The main treatment for choreatic movements associated to Huntington s disease are the neuroleptic drugs, however, its use causes long term troubles. We describe two patients with a predominantly choreic Huntington s disease, who experience improvement of choreatic movements after introduction of olanzapine to their treatment, being this drug well tolerated. The improvement of chorea suggests that olanzapine has a dopaminergic D2 receptors blocking action.

  12. Oily nanosuspension for long-acting intramuscular delivery of curcumin didecanoate prodrug: preparation, characterization and in vivo evaluation.

    Science.gov (United States)

    Wei, Xiao-Lan; Han, Ying-Rui; Quan, Li-Hui; Liu, Chun-Yu; Liao, Yong-Hong

    2013-05-13

    The objective of this study was to prepare the nanocrystals of curcumin didecanoate (CurDD) by wet ball milling and to investigate the comparative pharmacokinetics of oily nano- and micro-suspensions after intramuscular (i.m.) administration to rats. Upon optimizing the wet ball milling parameters, CurDD nanocrystals were produced with median particle size of ~500 nm and the freeze-dried nanocrystals were readily dispersed in peanut oil to form stable nanosuspensions. Although the nanosuspension appeared to exhibit slower clearance from the injection site after i.m. injection, compared to microsuspension (~5 μm), a significantly higher maximum plasma curcumin concentration (69.0 ng/ml) was observed for the former than that for the latter (18.5 ng/ml). In addition, the nanosuspension provided significant higher plasma curcumin concentrations and brain CurDD contents for at least 15 days than the microsuspension, except for the initial times. A single i.m. injection of nanosuspension appeared to achieve reversal effect on reserpine-induced hypothermia for at least 13 days. This study demonstrates that CurDD nanosuspension may act as a long-acting i.m. injectable for sustained delivery of curcumin, potentially applicable to elicit a long-lasting antidepressant effect.

  13. Intramuscular Olanzapine – a UK case series of early cases

    Directory of Open Access Journals (Sweden)

    Taylor Mark

    2007-04-01

    Full Text Available Abstract Background Clinical trials assessing efficacy and safety of Intramuscular (IM Olanzapine in acute schizophrenia and acute mania have previously been undertaken in studies required for drug registration in patients who were required to give informed consent. These patients may have less severe forms of psychosis than patients treated in routine practice. Data derived from naturalistic practice following the launch of IM olanzapine may be helpful for clinicians in assessing efficacy and safety of IM olanzapine. The PANSS-EC scale used in the clinical studies may represent a tool that could be used in routine clinical practice. Case presentation We report on an early unselected case series of 7 patients who received IM olanzapine in routine clinical practice settings in the UK. In this case series, olanzapine IM was generally effective, and no adverse events were reported. Adjunctive benzodiazepines were given concomitantly in 1 of the 7 subjects. This is relevant as concomitant benzodiazepines are not recommended for a minimum of 1 hour post IM olanzapine administration. PANSS-EC data was collected in 2 of the 7 subjects. Conclusion Although patients had greater severity of psychosis than clinical trial patients there were no unexpected findings. In addition the PANSS-EC scale is a scale that may be useful in assessing the efficacy of IM antipsychotics in routine clinical practice.

  14. Impact of pay for performance on prescribing of long-acting reversible contraception in primary care: an interrupted time series study.

    Directory of Open Access Journals (Sweden)

    Myat E Arrowsmith

    Full Text Available BACKGROUND: The aim of this study was to evaluate the impact of Quality and Outcomes Framework (QOF, a major pay-for-performance programme in the United Kingdom, on prescribing of long-acting reversible contraceptives (LARC in primary care. METHODS: Negative binomial interrupted time series analysis using practice level prescribing data from April 2007 to March 2012. The main outcome measure was the prescribing rate of long-acting reversible contraceptives (LARC, including hormonal and non hormonal intrauterine devices and systems (IUDs and IUSs, injectable contraceptives and hormonal implants. RESULTS: Prescribing rates of Long-Acting Reversible Contraception (LARC were stable before the introduction of contraceptive targets to the QOF and increased afterwards by 4% annually (rate ratios  = 1.04, 95% CI = 1.03, 1.06. The increase in LARC prescribing was mainly driven by increases in injectables (increased by 6% annually, which was the most commonly prescribed LARC method. Of other types of LARC, the QOF indicator was associated with a step increase of 20% in implant prescribing (RR =  1.20, 95% CI =  1.09, 1.32. This change is equivalent to an additional 110 thousand women being prescribed with LARC had QOF points not been introduced. CONCLUSIONS: Pay for performance incentives for contraceptive counselling in primary care with women seeking contraceptive advice has increased uptake of LARC methods.

  15. Characteristics of women in the United States who use long-acting reversible contraceptive methods.

    Science.gov (United States)

    Kavanaugh, Megan L; Jerman, Jenna; Hubacher, David; Kost, Kathryn; Finer, Lawrence B

    2011-06-01

    To examine characteristics of U.S. women that are associated with use of long-acting reversible contraception and changes in these characteristics between 2002 and 2006-2008. We analyzed data from two nationally representative samples of women aged 15-44 in the National Survey of Family Growth, including 7,643 women in 2002 and 7,356 women in 2006-2008. We conducted simple and multinomial logistic regression analyses to identify demographic and reproductive health characteristics associated with use of long-acting reversible contraception. Long-acting reversible contraception (intrauterine devices and subdermal implants) use among U.S. women using contraception increased from 2.4% in 2002 to 5.6% in 2006-2008. The largest increases in long-acting reversible contraception use during this time occurred among the youngest and oldest age groups, non-Hispanic white and non-Hispanic African American women, foreign-born women, and those in the highest income group. High prevalence of long-acting reversible contraception use in 2006-2008 was seen among women who had given birth once or twice (10%), foreign-born women (8.8%), and Hispanic women (8.4%). After adjusting for key demographic and reproductive health characteristics, in comparison with users of other contraceptive methods and with those not using contraception who were at risk for unintended pregnancy, foreign-born women and women who experienced coitarche before age 18 were approximately twice as likely to be using long-acting reversible contraception as women without those characteristics. A more diverse population of women used long-acting reversible contraception in 2006-2008 compared with 2002. However, there is likely more potential for increased uptake, especially among populations historically not considered to be candidates for these methods.

  16. A randomized, double-blind, placebo-controlled study of rapid-acting intramuscular olanzapine in Japanese patients for schizophrenia with acute agitation

    Directory of Open Access Journals (Sweden)

    Katagiri Hideaki

    2013-01-01

    Full Text Available Abstract Background Olanzapine rapid-acting intramuscular (IM injection is an atypical antipsychotic drug already used overseas and recently approved in Japan. The objective of this study was to confirm the efficacy of rapid-acting IM olanzapine 10 mg was greater than IM placebo in patients with exacerbation of schizophrenia with acute psychotic agitation by comparing changes from baseline to 2 hours after the first IM injection, as measured by the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC total score. Methods We conducted a placebo-controlled, randomized, double-blind, parallel-group study in Japanese patients diagnosed with schizophrenia according to the diagnostic criteria specified in the DSM-IV-TR. Patients were randomized to 2 treatment groups: IM olanzapine (10 mg or IM placebo. The primary efficacy outcome was the change in PANSS-EC from baseline to 2 hours after the first IM injection. Treatment groups were compared with an analysis of variance model which included treatment and site as factors. During the 24-hour treatment period, safety was assessed by clinical examination and laboratory investigations, electrocardiograms, extrapyramidal symptoms scales, and recording spontaneously reported adverse events. Results Of the 91 randomized patients, 90 patients (45 IM olanzapine-group; 45 IM placebo-group were in the full analysis set. The mean change of PANSS-EC total score from baseline to 2 hours after the first IM injection (mean±standard deviation was −9.2±4.5 for the IM olanzapine group and −2.8±5.6 for the IM placebo group. The difference between treatment groups was statistically significant (p Conclusion The efficacy of IM olanzapine 10 mg in patients with exacerbation of schizophrenia with acute psychotic agitation was greater than IM placebo in the primary efficacy measure, PANSS-EC. Intramuscular olanzapine 10 mg was shown to be generally safe and tolerable, and could be a new option for treatment

  17. Preventing olanzapine-induced weight gain using betahistine: a study in a rat model with chronic olanzapine treatment.

    Science.gov (United States)

    Lian, Jiamei; Huang, Xu-Feng; Pai, Nagesh; Deng, Chao

    2014-01-01

    Olanzapine is the one of first line antipsychotic drug for schizophrenia and other serious mental illness. However, it is associated with troublesome metabolic side-effects, particularly body weight gain and obesity. The antagonistic affinity to histamine H1 receptors (H1R) of antipsychotic drugs has been identified as one of the main contributors to weight gain/obesity side-effects. Our previous study showed that a short term (2 weeks) combination treatment of betahistine (an H1R agonist and H3R antagonist) and olanzapine (O+B) reduced (-45%) body weight gain induced by olanzapine in drug-naïve rats. A key issue is that clinical patients suffering with schizophrenia, bipolar disease and other mental disorders often face chronic, even life-time, antipsychotic treatment, in which they have often had previous antipsychotic exposure. Therefore, we investigated the effects of chronic O+B co-treatment in controlling body weight in female rats with chronic and repeated exposure of olanzapine. The results showed that co-administration of olanzapine (3 mg/kg, t.i.d.) and betahistine (9.6 mg/kg, t.i.d.) significantly reduced (-51.4%) weight gain induced by olanzapine. Co-treatment of O+B also led to a decrease in feeding efficiency, liver and fat mass. Consistently, the olanzapine-only treatment increased hypothalamic H1R protein levels, as well as hypothalamic pAMPKα, AMPKα and NPY protein levels, while reducing the hypothalamic POMC, and UCP1 and PGC-1α protein levels in brown adipose tissue (BAT). The olanzapine induced changes in hypothalamic H1R, pAMPKα, BAT UCP1 and PGC-1α could be reversed by co-treatment of O+B. These results supported further clinical trials to test the effectiveness of co-treatment of O+B for controlling weight gain/obesity side-effects in schizophrenia with chronic antipsychotic treatment.

  18. The Contraceptive CHOICE Project: reducing barriers to long-acting reversible contraception.

    Science.gov (United States)

    Secura, Gina M; Allsworth, Jenifer E; Madden, Tessa; Mullersman, Jennifer L; Peipert, Jeffrey F

    2010-08-01

    To introduce and promote the use of long-acting reversible methods of contraception (LARC; intrauterine contraceptives and subdermal implant) by removing financial and knowledge barriers. The Contraceptive CHOICE Project is a prospective cohort study of 10,000 women 14-45 years who want to avoid pregnancy for at least 1 year and are initiating a new form of reversible contraception. Women screened for this study are read a script regarding long-acting reversible methods of contraception to increase awareness of these options. Participants choose their contraceptive method that is provided at no cost. We report the contraceptive choice and baseline characteristics of the first 2500 women enrolled August 2007 through December 2008. Sixty-seven percent of women enrolled (95% confidence interval, 65.3-69.0) chose long-acting methods. Fifty-six percent selected intrauterine contraception and 11% selected the subdermal implant. Once financial barriers were removed and long-acting reversible methods of contraception were introduced to all potential participants as a first-line contraceptive option, two-thirds chose long-acting reversible methods of contraception. Copyright (c) 2010 Mosby, Inc. All rights reserved.

  19. Contraception Insurance Coverage and Receipt of Long-Acting Reversible Contraception or Depot Medroxyprogesterone Acetate on the Day of Abortion.

    Science.gov (United States)

    Krashin, Jamie W; Stuart, Gretchen S; Garrett, Joanne; Spector, Hannah; Bryant, Amy G; Charm, Samantha; Morse, Jessica E

    2017-07-01

    To evaluate whether contraceptive insurance coverage for women who present for an abortion is associated with obtaining long-acting reversible contraception or depot medroxyprogesterone acetate (DMPA) on the day the abortion is completed. We conducted a prospective cohort study of women presenting for medical or surgical abortion at a single health center in North Carolina. Eligible women were 18 years or older and fluent in English or Spanish. Data were from participant questionnaires, medical charts, and financial records. Our main exposure was whether the woman had insurance coverage for contraception at clinic intake. Our primary outcome was receiving DMPA, an intrauterine device, or a contraceptive subdermal implant on the same day of their surgical abortion or at the visit that determined their medication abortion was complete. We used univariable, bivariable, and multivariable analysis to report our findings. Five hundred seventy-five women enrolled in our cohort between September 2015 and April 2016. One hundred twenty-eight (22%) had insurance coverage and 447 (78%) did not. In the group with insurance coverage for contraception, 38% (49/128) received a long-acting reversible contraception method or DMPA compared with 7% (33/447) in the group without insurance coverage for contraception. After adjusting for confounding, women with contraceptive coverage were more than five times as likely to receive immediate postabortion contraception with one of these methods compared with women without coverage (relative risk 5.6, 95% confidence interval 3.8-8.3). Women with contraceptive insurance coverage on the day of their abortion were more likely to leave the abortion clinic with an intrauterine device or implant in place or receive DMPA injection compared with women without coverage.

  20. Conversion of daily pegvisomant to weekly pegvisomant combined with long-acting somatostatin analogs, in controlled acromegaly patients.

    Science.gov (United States)

    Neggers, Sebastian J C M M; de Herder, Wouter W; Feelders, Richard A; van der Lely, A J

    2011-09-01

    The efficacy of combined treatment in active acromegaly with both long-acting somatostatin analogs (SRIF) and pegvisomant (PEG-V) has been well established. The aim was to describe the PEG-V dose reductions after the conversion from daily PEG-V to combination treatment. To clarify the individual beneficial and adverse effects, in two acromegaly patients, who only normalized their insulin like growth factor (IGF-I) levels with high-dose pegvisomant therapy. We present two cases of a 31 and 44 years old male with gigantism and acromegaly that were controlled subsequently by surgery, radiotherapy, SRIF analogs and daily PEG-V treatment. They were converted to combined treatment of monthly SSA and (twice) weekly PEG-V. High dose SSA treatment was added while the PEG-V dose was decreased during carful monitoring of the IGF-I. After switching from PEG-V monotherapy to SRIF analogs plus pegvisomant combination therapy IGF-I remained normal. However, the necessary PEG-V dose, to normalize IGF-I differed significantly between these two patients. One patient needed twice weekly 100 mg, the second needed 60 mg once weekly on top of their monthly lanreotide Autosolution injections of 120 mg. The weekly dose reduction was 80 and 150 mg. After the introducing of lanreotide, fasting glucose and glycosylated haemoglobin concentrations increased. Diabetic medication had to be introduced or increased. No changes in liver tests or in pituitary adenoma size were observed. In these two patients, PEG-V in combination with long-acting SRIF analogs was as effective as PEG-V monotherapy in normalizing IGF-I levels, although significant dose-reductions in PEG-V could be achieved. However, there seems to be a wide variation in the reduction of PEG-V dose, which can be obtained after conversion to combined treatment.

  1. Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations

    Science.gov (United States)

    The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrino...

  2. Once-daily glycopyrronium bromide, a long-acting muscarinic antagonist, for chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli

    2012-01-01

    Long-acting bronchodilators are central in the pharmacological management of patients with chronic obstructive pulmonary disease (COPD). The aim of this systematic review is to provide an overview of the studies evaluating the safety and clinical efficacy of inhaled glycopyrronium bromide, a novel...

  3. Differences in acute anorectic effects of long-acting GLP-1 receptor agonists in rats

    Science.gov (United States)

    Long-acting glucagon-like peptide-1 receptor (GLP-1R) agonists have both glucose- and weight-lowering effects. The brain is poised to mediate both of these actions since GLP-1Rs are present in key areas known to control weight and glucose. Although some research has been performed on the effects of ...

  4. Long-acting β-adrenoceptor agonists in the management of COPD: focus on indacaterol

    Science.gov (United States)

    Beier, Jutta; Beeh, Kai M

    2011-01-01

    Bronchodilators are the cornerstone of severe chronic obstructive pulmonary disease (COPD) treatment to improve airflow, symptoms, exercise tolerance, and exacerbations. There is convincing evidence that regular treatment with long-acting bronchodilators is more effective and convenient than treatment with short-acting bronchodilators. Long-acting β-2-agonists include the twice-daily drugs formoterol and salmeterol and, more recently, once-daily indacaterol. Studies with head-to-head comparisons of long-acting bronchodilators are scant, but novel data from controlled trials with the once-daily β(2)-agonist indacaterol indicate superior bronchodilation and clinical efficacy of indacaterol at recommended doses over twice-daily long-acting β(2)-agonists, and at least equipotent bronchodilation compared with once-daily tiotropium. The recent therapeutic developments in COPD underscore a shift from short-acting bronchodilators with multiple dosings per day to reduced dosing frequency and prolonged duration of action, including once-daily treatment, with more consistent effects on various clinical outcomes. This review summarizes relevant clinical data for twice-daily β-2-agonists in COPD, and further focuses on novel data for once-daily indacaterol, including head-to-head comparison trials. PMID:21814459

  5. Does Prolonged Therapy with a Long-Acting Stimulant Suppress Growth in Children with ADHD?

    Science.gov (United States)

    Spencer, Thomas J.; Faraone, Stephen V.; Biederman, Joseph; Lerner, Marc; Cooper, Kimberly M.; Zimmerman, Brenda

    2006-01-01

    Objective: To investigate whether prolonged therapy with a long-acting stimulant affects growth in children with attention-deficit/hyperactivity disorder (ADHD). Method: One hundred seventy-eight children ages 6 to 13 years received OROS methylphenidate (OROS MPH, CONCERTA) for at least 21 months. Height and weight were measured monthly during the…

  6. How Do Dual Long-acting Bronchodilators Prevent Exacerbations of Chronic Obstructive Pulmonary Disease?

    DEFF Research Database (Denmark)

    Beeh, Kai M; Burgel, Pierre-Regis; Franssen, Frits M E;

    2016-01-01

    Decreasing the frequency and severity of exacerbations is one of the main goals of treatment for patients with chronic obstructive pulmonary disease (COPD). Several studies have documented that long-acting bronchodilators (LABDs) can reduce exacerbation rate and/or severity, and others have shown...

  7. Long-acting reversible contraceptives: intrauterine devices and the contraceptive implant.

    Science.gov (United States)

    Espey, Eve; Ogburn, Tony

    2011-03-01

    The provision of effective contraception is fundamental to the practice of women's health care. The most effective methods of reversible contraception are the so-called long-acting reversible contraceptives, intrauterine devices and implants. These methods have multiple advantages over other reversible methods. Most importantly, once in place, they do not require maintenance and their duration of action is long, ranging from 3 to 10 years. Despite the advantages of long-acting reversible contraceptive methods, they are infrequently used in the United States. Short-acting methods, specifically oral contraceptives and condoms, are by far the most commonly used reversible methods. A shift from the use of short-acting methods to long-acting reversible contraceptive methods could help reduce the high rate of unintended pregnancy in the United States. In this review of long-acting reversible contraceptive methods, we discuss the intrauterine devices and the contraceptive implant available in the United States, and we describe candidates for each method, noncontraceptive benefits, and management of complications.

  8. The long-acting somatostatin analogue SMS 201-995 causes malabsorption

    DEFF Research Database (Denmark)

    Witt, K; Pedersen, N T

    1989-01-01

    Somatostatin and its long-acting analogue SMS 201-995 (Sandostatin) have been suspected of causing steatorrhoea. The aim of this study was to examine the effect of SMS 201-995 on fat assimilation in healthy subjects, using 14C-triolein and 3H-oleic acid as tracers of dietary triglycerides and free...

  9. Long-acting somatostatin analog therapy of acromegaly: A meta-analysis

    NARCIS (Netherlands)

    P.U. Freda (Pamela); L. Katznelson (Laurence); A-J. van der Lely (Aart-Jan); F. Reyes; S. Zhao (Shouhao); D. Rabinowitz (Daniel)

    2005-01-01

    textabstractContext: Although considerable data exist on the use of long-acting somatostatin analogs to treat acromegaly, their reported efficacy differs substantially among trials. Objective: We conducted a meta-analysis to derive definitive estimates of their efficacy for biochemical control and

  10. Number needed to treat and number needed to harm with paliperidone palmitate relative to long-acting haloperidol, bromperidol, and fluphenazine decanoate for treatment of patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Srihari Gopal

    2011-03-01

    Full Text Available Srihari Gopal1, Joris Berwaerts1, Isaac Nuamah1, Kasem Akhras2, Danielle Coppola1, Ella Daly1, David Hough1, Joseph Palumbo11Johnson & Johnson Pharmaceutical Research & Development, LLC, Raritan, NJ, USA; 2Johnson & Johnson Pharmaceutical Services, LLC, Raritan, NJ, USABackground: We analyzed data retrieved through a PubMed search of randomized, placebo-controlled trials of first-generation antipsychotic long-acting injectables (haloperidol decanoate, bromperidol decanoate, and fluphenazine decanoate, and a company database of paliperidone palmitate, to compare the benefit-risk ratio in patients with schizophrenia.Methods: From the eight studies that met our selection criteria, two efficacy and six safety parameters were selected for calculation of number needed to treat (NNT, number needed to harm (NNH, and the likelihood of being helped or harmed (LHH using comparisons of active drug relative to placebo. NNTs for prevention of relapse ranged from 2 to 5 for paliperidone palmitate, haloperidol decanoate, and fluphenazine decanoate, indicating a moderate to large effect size.Results: Among the selected maintenance studies, NNH varied considerably, but indicated a lower likelihood of encountering extrapyramidal side effects, such as akathisia, tremor, and tardive dyskinesia, with paliperidone palmitate versus placebo than with first-generation antipsychotic depot agents versus placebo. This was further supported by an overall higher NNH for paliperidone palmitate versus placebo with respect to anticholinergic use and Abnormal Involuntary Movement Scale positive score. LHH for preventing relapse versus use of anticholinergics was 15 for paliperidone palmitate and 3 for fluphenazine decanoate, favoring paliperidone palmitate.Conclusion: Overall, paliperidone palmitate had a similar NNT and a more favorable NNH compared with the first-generation long-acting injectables assessed.Keywords: long-acting injectables, first-generation antipsychotics

  11. Formulation and characterization of nanoemulsion of olanzapine for intranasal delivery.

    Science.gov (United States)

    Kumar, Mukesh; Misra, Ambikanandan; Pathak, Kamla

    2009-01-01

    The objective was to formulate an olanzapine nanoemulsion that could potentially deliver the drug directly to the brain following intranasal administration. The nanoemulsions were prepared using the water titration method. The mucoadhesive character was imparted by the addition of 0.5%w/w chitosan and 0.5%w/w polycarbophil and was characterized for drug content, pH, percentage transmittance, globule size, zeta potential, and PDI. The composition (%w/w) of the optimized olanzapine nanoemulsion was capmul MCM, tween 80, and a mixture of 1:1 ratio of polyethylene glycol 400 and ethanol, and aqueous phase in a ratio of 15:35:17.5:32.5. The optimized olanzapine nanoemulsion exhibited a high diffusion coefficient and no nasal cilio-toxicity. The drug release followed the Higuchi model. The optimized nanoemulsions were found to be stable for 3 months.

  12. Pharmacokinetics of a long-acting ceftiofur formulation (ceftiofur crystalline free acid) in the ball python (Python regius).

    Science.gov (United States)

    Adkesson, Michael J; Fernandez-Varon, Emilio; Cox, Sherry; Martín-Jiménez, Tomás

    2011-09-01

    The objective of this study was to determine the pharmacokinetics of a long-acting formulation of ceftiofur crystalline-free acid (CCFA) following intramuscular injection in ball pythons (Python regius). Six adult ball pythons received an injection of CCFA (15 mg/kg) in the epaxial muscles. Blood samples were collected by cardiocentesis immediately prior to and at 0.5, 1, 2, 4, 8, 12, 18, 24, 48, 72, 96, 144, 192, 240, 288, 384, 480, 576, 720, and 864 hr after CCFA administration. Plasma ceftiofur concentrations were determined by high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis was applied to the data. Maximum plasma concentration (Cmax) was 7.096 +/- 1.95 microg/ml and occurred at (Tmax) 2.17 +/- 0.98 hr. The area under the curve (0 to infinity) for ceftiofur was 74.59 +/- 13.05 microg x h/ml and the elimination half-life associated with the terminal slope of the concentration-time curve was 64.31 +/- 14.2 hr. Mean residence time (0 to infinity) was 46.85 +/- 13.53 hr. CCFA at 15 mg/kg was well tolerated in all the pythons. Minimum inhibitory concentration (MIC) data for bacterial isolates from snakes are not well established. For MIC values of python. For MICs > or =0.5 microg/ml, more frequent dosing or a higher dosage may be required.

  13. Late Onset Anorexia Nervosa Treated With Olanzapine: A Case Report

    Directory of Open Access Journals (Sweden)

    Paolo Santonastaso

    2008-12-01

    Full Text Available A case of late onset anorexia nervosa (AN treated with olanzapine is reported. The patient suffered AN onset at the age of 53 and was brought to our attention four years later in a very poor state of health due to extreme starvation and laxative abuse. She presented severe obsessions about food, a very disturbed body image, and “ascetic” rituals of self-punishment. There was no improvement of her symptoms with cognitive behavioural therapy, antidepressant drugs and inpatient nutritional therapy. After the prescription of olanzapine, the patient was more cooperative and able to maintain a stable acceptable weight, although her psychiatric and anorexic symptoms only improved partially.

  14. Atypicality in presentation of neuroleptic malignant syndrome caused by olanzapine

    Directory of Open Access Journals (Sweden)

    Mishra Biswaranjan

    2007-10-01

    Full Text Available Neuroleptic malignant syndrome (NMS is the most serious of acute neurological side effects produced by antipsychotic medication, characterized by hyperthermia, rigidity, altered consciousness and autonomic dysfunction, the prevalence of which varies from 0.4-1.4%. NMS is usually seen in treatment with high potency typical antipsychotics and very rarely with atypical antipsychotics. However, NMS cases have been reported with risperidone, clozapine, olanzapine and quetiapine. The presentations of NMS have often varied, and we report another atypicality in presentation of NMS due to olanzapine use.

  15. Metabolic and behavioral effects of chronic olanzapine treatment and cafeteria diet in rats.

    Science.gov (United States)

    Muller, Alexandre P; Tort, Ana H; Gnoatto, Jussânia; Moreira, Julia D; Vinadé, Elsa R; Perry, Marcos L; Souza, Diogo O; Lara, Diogo R; Portela, Luis V

    2010-10-01

    Olanzapine and highly palatable diets can alter metabolism and brain function. We investigated the interaction of chronic treatment (4 months) with olanzapine and a cafeteria diet on metabolic parameters, memory tasks (spatial and aversive), the elevated plus maze and locomotor activity induced by d-amphetamine. Male Wistar rats were separated into the following groups: standard diet vehicle, standard diet and olanzapine, cafeteria diet vehicle and cafeteria diet and olanzapine. Olanzapine was administered in the drinking water (approximately 1.5 mg/kg/day), and after 3 days of treatment, the rats exhibited an expected anxiolytic effect and reduced amphetamine-induced hyperlocomotion. After 4 months of treatment, cafeteria diet vehicle and cafeteria diet olanzapine rats exhibited an increased body weight and heavier fat pads compared with the standard diet groups. Olanzapine increased only the epididymal and mesenteric fat pads. The cafeteria diet and olanzapine group showed greater glucose intolerance compared with all other groups. The cafeteria diet altered the effects of chronic olanzapine on the performance in the water maze and inhibitory avoidance tasks. Chronic olanzapine treatment failed to affect amphetamine-induced locomotion and to produce anxiolytic effects in the elevated plus maze task, regardless of the diet. Our results suggest that chronic olanzapine caused an increase in fat pads, which is putatively involved in the etiology of many metabolic diseases. Rats on the cafeteria diet were overweight and exhibited glucose intolerance. We did not observe these effects with olanzapine treatment with the standard diet. Moreover, the chronic treatment regimen caused tolerance to the antipsychotic and anxiolytic effects of olanzapine and seemed to potentiate some of the metabolic effects of the cafeteria diet. The cafeteria diet also modified the effects of chronic treatment with olanzapine on cognitive tasks, which may represent an undesirable effect of

  16. Preventing olanzapine-induced weight gain using betahistine: a study in a rat model with chronic olanzapine treatment.

    Directory of Open Access Journals (Sweden)

    Jiamei Lian

    Full Text Available Olanzapine is the one of first line antipsychotic drug for schizophrenia and other serious mental illness. However, it is associated with troublesome metabolic side-effects, particularly body weight gain and obesity. The antagonistic affinity to histamine H1 receptors (H1R of antipsychotic drugs has been identified as one of the main contributors to weight gain/obesity side-effects. Our previous study showed that a short term (2 weeks combination treatment of betahistine (an H1R agonist and H3R antagonist and olanzapine (O+B reduced (-45% body weight gain induced by olanzapine in drug-naïve rats. A key issue is that clinical patients suffering with schizophrenia, bipolar disease and other mental disorders often face chronic, even life-time, antipsychotic treatment, in which they have often had previous antipsychotic exposure. Therefore, we investigated the effects of chronic O+B co-treatment in controlling body weight in female rats with chronic and repeated exposure of olanzapine. The results showed that co-administration of olanzapine (3 mg/kg, t.i.d. and betahistine (9.6 mg/kg, t.i.d. significantly reduced (-51.4% weight gain induced by olanzapine. Co-treatment of O+B also led to a decrease in feeding efficiency, liver and fat mass. Consistently, the olanzapine-only treatment increased hypothalamic H1R protein levels, as well as hypothalamic pAMPKα, AMPKα and NPY protein levels, while reducing the hypothalamic POMC, and UCP1 and PGC-1α protein levels in brown adipose tissue (BAT. The olanzapine induced changes in hypothalamic H1R, pAMPKα, BAT UCP1 and PGC-1α could be reversed by co-treatment of O+B. These results supported further clinical trials to test the effectiveness of co-treatment of O+B for controlling weight gain/obesity side-effects in schizophrenia with chronic antipsychotic treatment.

  17. PHARMACOKINETICS OF CEFTIOFUR CRYSTALLINE FREE ACID, A LONG-ACTING CEPHALOSPORIN, IN AMERICAN FLAMINGOS (PHOENICOPTERUS RUBER).

    Science.gov (United States)

    Kilburn, Jennifer J; Cox, Sherry K; Backues, Kay A

    2016-06-01

    Antibiotic usage is a vital component of veterinary medicine but the unique anatomy of some species can make administration difficult. The objective of this study was to determine the pharmacokinetic parameters of ceftiofur crystalline free acid (CCFA), a long-acting cephalosporin antibiotic, after parenteral administration in American flamingos ( Phoenicopterus ruber ). A dose of 10 mg/kg of CCFA was administered intramuscularly to 11 birds and blood was collected at various time points from 0 to 192 hr. Pharmacokinetic parameters for ceftiofur equivalents were determined and reached levels above minimum inhibitory concentrations of various bacterial organisms in other avian species through 96 hr in 9/11 birds. Based on these findings and comparison to other avian studies, ceftiofur crystalline free acid appears to be a long-acting antibiotic option for American flamingos. Administration of this antibiotic should be utilized in conjunction with culture and sensitivity of suspected pathogens.

  18. Long-acting muscarinic antagonists vs. long-acting β 2 agonists in COPD exacerbations: a systematic review and meta-analysis.

    Science.gov (United States)

    Maia, Israel Silva; Pincelli, Mariângela Pimentel; Leite, Victor Figueiredo; Amadera, João; Buehler, Anna Maria

    2017-07-31

    To determine whether long-acting muscarinic antagonists (LAMAs) provide superior therapeutic effects over long-acting β2 agonists (LABAs) for preventing COPD exacerbations. This was a systematic review and meta-analysis of randomized clinical trials involving patients with stable, moderate to severe COPD according to the Global Initiative for Chronic Obstructive Lung Disease criteria, treated with a LAMA (i.e., tiotropium bromide, aclidinium, or glycopyrronium), followed for at least 12 weeks and compared with controls using a LABA in isolation or in combination with a corticosteroid. A total of 2,622 studies were analyzed for possible inclusion on the basis of their title and abstract; 9 studies (17,120 participants) were included in the analysis. In comparison with LABAs, LAMAs led to a greater decrease in the exacerbation rate ratio (relative risk [RR] = 0.88; 95% CI: 0.84-0.93]; a lower proportion of patients who experienced at least one exacerbation (RR = 0.90; 95% CI: 0.87-0.94; p eventos adversos sérios (RR = 0,81; IC95%: 0,67-0,96; p = 0,0002). A qualidade geral das evidências foi moderada para todos os desfechos. O principal achado desta revisão sistemática e meta-análise foi que LAMAs reduziram significativamente a taxa de exacerbações (episódios de exacerbação/ano), os episódios de exacerbação, as hospitalizações e os eventos adversos sérios.

  19. Pharmacokinetics of Long-Acting Tenofovir Alafenamide (GS-7340) Subdermal Implant for HIV Prophylaxis

    OpenAIRE

    Gunawardana, Manjula; Remedios-Chan, Mariana; Miller, Christine S.; Fanter, Rob; Yang, Flora; Marzinke, Mark A.; Hendrix, Craig W.; Beliveau, Martin; John A Moss; Thomas J Smith; Marc M Baum

    2015-01-01

    Oral or topical daily administration of antiretroviral (ARV) drugs to HIV-1-negative individuals in vulnerable populations is a promising strategy for HIV-1 prevention. Adherence to the dosing regimen has emerged as a critical factor determining efficacy outcomes of clinical trials. Because adherence to therapy is inversely related to the dosing period, sustained release or long-acting ARV formulations hold significant promise for increasing the effectiveness of HIV-1 preexposure prophylaxis ...

  20. Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations

    DEFF Research Database (Denmark)

    Christiansen, Jens Sandahl; Backeljauw, Philippe F; Bidlingmaier, Martin

    2016-01-01

    OBJECTIVE: The Growth Hormone (GH) Research Society convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting GH preparations (LAGH). PARTICIPANTS: A closed meeting of 55 international scientists with expertise in growth hormone, including pediatric...... and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. EVIDENCE: Current literature was reviewed for gaps in knowledge. Expert opinion was utilized to suggest studies required to address potential safety and efficacy issues. CONSENSUS PROCESS...

  1. Risk of extrapyramidal syndromes with haloperidol, risperidone, or olanzapine

    NARCIS (Netherlands)

    Schillevoort, I; de Boer, A; Herings, R M; Roos, R A; Jansen, P A; Leufkens, H G

    2001-01-01

    OBJECTIVE: To compare the risk of extrapyramidal syndrome (EPS) between risperidone, olanzapine, and haloperidol, taking into account patients' past antipsychotic drug use and past EPS. METHODS: Data were obtained from the PHARMO-database, containing filled prescriptions of 450,000

  2. Olanzapine-induced tender pitting pre-tibial edema

    Directory of Open Access Journals (Sweden)

    Kaliaperumal Mathan

    2015-01-01

    Full Text Available Antipsychotic-induced edema is uncommonly encountered in clinical practice. We report a case of tender pitting pre-tibial edema with olanzapine in a woman with no medical comorbidities. The peculiar distribution of edema resulted in diagnostic confusion necessitating specific investigations. Eventually, the edema resolved following complete stoppage of the drug, but caused distress to the patient and the caregiver.

  3. Risk of extrapyramidal syndromes with haloperidol, risperidone, or olanzapine

    NARCIS (Netherlands)

    Schillevoort, I; de Boer, A; Herings, R M; Roos, R A; Jansen, P A; Leufkens, H G

    2001-01-01

    OBJECTIVE: To compare the risk of extrapyramidal syndrome (EPS) between risperidone, olanzapine, and haloperidol, taking into account patients' past antipsychotic drug use and past EPS. METHODS: Data were obtained from the PHARMO-database, containing filled prescriptions of 450,000 community-dwellin

  4. The Effect of Ranitidine on Olanzapine-Induced Weight Gain

    Directory of Open Access Journals (Sweden)

    Fatemeh Ranjbar

    2013-01-01

    Full Text Available Induced weight gain is a disturbing side effect of Olanzapine that affects the quality of life in psychotic patients. The aim of this study was to assess the efficacy of Ranitidine in attenuating or preventing Olanzapine-induced weight gain. A parallel 2-arm clinical trial was done on 52 patients with schizophrenia, schizoaffective and schizophreniform disorders who received Olanzapine for the first time. All these were first-episode admitted patients. They were randomly allocated to receive either Ranitidine or placebo. The trend of body mass index (BMI was compared between groups over 16-week course of treatment. Mean weight was 62.3 (SD: 9.6 kg at baseline. Thirty-three subjects (63.5% had positive family history of obesity. The average BMI increment was 1.1 for Ranitidine group and 2.4 for the placebo group. The multivariate analysis showed this effect to be independent of sex, family history of obesity, and baseline BMI value. The longitudinal modeling after controlling for baseline values failed to show the whole trend slope to be different. Although the slight change in trend’s slope puts forward a hypothesis that combined use of Ranitidine and Olanzapine may attenuate the weight gain long run, this needs to be retested in future larger scale long-term studies. This trial is registered with IRCT.ir 201009112181N5.

  5. Serum ghrelin levels in acromegaly: effects of surgical and long-acting octreotide therapy.

    Science.gov (United States)

    Freda, Pamela U; Reyes, Carlos M; Conwell, Irene M; Sundeen, Robert E; Wardlaw, Sharon L

    2003-05-01

    The orexigenic peptide, ghrelin, is regulated by acute and chronic nutritional state. Although exogenously administered ghrelin stimulates pituitary GH secretion, little is known about the role of ghrelin in endogenous GH secretion or how high GH and IGF-I levels in acromegaly could affect ghrelin secretion and vice versa. Therefore, we evaluated fasting and post oral glucose tolerance test serum ghrelin levels in 19 patients with active acromegaly at baseline and after either surgery in 9 of these or administration of long-acting octreotide (Sandostatin LAR) in the other 10 patients. After surgical cure, fasting ghrelin rose from 312 +/- 56 pg/ml to 548 +/- 97 pg/ml (P = 0.013). Fasting serum ghrelin levels were higher in all patients after surgery and ranged between 112% and 349% of presurgery levels. Ghrelin levels fell significantly during long-acting octreotide therapy from 447 +/- 34 pg/ml to 206 +/- 15 pg/ml (P acromegaly; lowered serum levels of ghrelin in active acromegaly rise along with the postsurgery normalization of GH and IGF-I and improved insulin resistance. In contrast to surgical therapy, long-acting octreotide therapy persistently suppressed serum ghrelin levels. It remains to be determined whether altered circulating ghrelin concentrations could impact on body composition changes in acromegaly.

  6. Preparation, characterization and related in vivo release, safety and toxicity studies of long acting lanreotide microspheres.

    Science.gov (United States)

    Wang, Shuang; Wu, Mingsheng; Li, Dan; Jiao, Mingli; Wang, Lan; Zhang, Haifeng; Liu, Huaiyu; Wang, Daifeng; Han, Bing

    2012-01-01

    The goal of this project was to prepare long-acting lanreotide acetate poly(lactic-co-glycolic acid) (PLGA) microspheres and to analyze the in vivo and in vitro release, safety and toxicology of these preparations. Long-acting lanreotide acetate PLGA microspheres that exhibited a 5-week slow-release period were prepared by a multiple-emulsion solvent evaporation method. Physical characterization, as well as the analysis of the in vivo and in vitro release, safety, acute toxicity and chronic toxicity of the lanreotide microspheres, were conducted in animal models in rats, guinea pigs, rabbits and beagle dogs. The lanreotide acetate PLGA microspheres prepared by multiple-emulsion solvent evaporation had smooth surfaces, uniform particle size and stable lanreotide loading. In vivo and in vitro experiments showed that the lanreotide acetate PLGA microspheres could continuously release lanreotide for 5 weeks. The safety of these long acting lanreotide microspheres was good in the following animal models: active systemic anaphylaxis test in guinea pigs, passive cutaneous anaphylaxis test in rats, hemolytic test in rabbits, local skin irritation test after subcutaneous administration in rabbits and muscle stimulation test in rabbits. Furthermore, no significant acute toxicity or chronic toxicity was observed after administration of lanreotide acetate PLGA microspheres in beagle dogs at dosages up to 22 mg/kg. The lanreotide acetate PLGA microspheres that were prepared in this study exhibited beneficial characteristics in apparent property and structural stability, as well as in release trends in vivo and in vitro.

  7. Targets, attitudes, and goals of psychiatrists treating patients with schizophrenia: key outcome drivers, role of quality of life, and place of long-acting antipsychotics

    Directory of Open Access Journals (Sweden)

    de Bartolomeis A

    2016-01-01

    Full Text Available Andrea de Bartolomeis,1 Andrea Fagiolini,2 Marco Vaggi,3 Claudio Vampini4 1Section of Psychiatry and Treatment Resistant Psychosis, Department of Neuroscience, University of Naples Federico II, Naples, Italy; 2Department of Molecular and Developmental Medicine, School of Medicine, University of Siena, Siena, Italy; 3Mental Health and Drug Addiction Department, Genovese, Genoa, Italy; 4Department of Mental Health, Ospedale Civile Maggiore and ULSS 20, Verona, Italy Purpose: This survey of Italian psychiatrists was conducted to better define drivers of schizophrenia treatment choice in real-life practice, particularly for use of long-acting injectable (LAI antipsychotics.Methods: Between October 15 and December 15, 2014, 1,000 surveys were sent to psychiatrists who treat schizophrenic patients; 709 completed questionnaires were analyzed (71% response rate.Results: The two most important factors determining therapy success were efficacy (75% of responses and tolerability (45% followed by global functioning (24% and quality of life (17%. LAI antipsychotics were most often used to facilitate regular treatment monitoring (49%, and 41% of psychiatrists thought that patients with low adherence who had failed oral therapy were well-suited for LAI antipsychotics. Only 4% of respondents saw LAI antipsychotics as appropriate for patients without other therapeutic options.Conclusion: Although efficacy and tolerability were the most common factors used to evaluate treatment success in schizophrenia, psychiatrists also consider QoL and global functioning to be important. Keywords: quality of life, long-acting injectable antipsychotics, schizophrenia, survey

  8. Introduction of postabortion contraception, prioritizing long-acting reversible contraceptives, in the principal maternity hospital of Gabon.

    Science.gov (United States)

    Mayi-Tsonga, Sosthène; Obiang, Pamphile Assoumou; Minkobame, Ulysse; Ngouafo, Doris; Ambounda, Nathalie; de Souza, Maria Helena

    2014-07-01

    A prospective, descriptive, analytic study was conducted at the Centre Hospitalier de Libreville in Gabon between February and September 2013 to evaluate acceptance of long-acting reversible contraceptives (LARC) and depot-medroxyprogesterone acetate (DMPA) following abortion. Women received counseling on the combined oral pill, DMPA, copper intrauterine devices (IUDs), and implants. The association between sociodemographic and clinical characteristics, knowledge of contraceptives, and acceptance was analyzed. Of the 383 women admitted with abortion complications, 206 (53.7%) knew of no systemic contraceptives. The best-known method was the oral pill (42.0%). Only 14 women (3.6%) knew of a LARC method (IUD or implants) and only 2 (0.5%) said the injectable was their best-known method. Over 90% accepted a modern contraceptive method after abortion. Two-thirds (66.8%) chose the pill, 14.6% DMPA, and 9.3% a LARC method. Only 9.1% of the women refused to initiate use of any method. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  9. EFFECT OF PREOPERATIVE USE OF LONG-ACTING OCTREOTIDE ON GROWTH HORMONE SECRETING PITUITARY ADENOMA AND TRANSSPHENOIDAL SURGERY

    Institute of Scientific and Technical Information of China (English)

    Jian Yin; Chang-bao Su; Zhi-qin Xu; Yi Yang; Wen-bin Ma; Wei Tao; Zhong Yang; Xue-wei Xia

    2005-01-01

    Objective To investigate whether somatostatin analog octreotide long acting release (LAR) shrinks growth hormone (GH) secreting adenomas, and improves the results of subsequent transsphenoidal surgery.Methods Seventeen previously untreated active acromegalic patients with pituitary adenomas were treated with LAR (30 mg intramuscular injection every 28 days) for 3 months prior to transsphenoidal surgery. Clinical reaction, mean GH secretion, and tumor volume were measured under basal conditions and after LAR treatment.Results Presurgical treatment improved acromegaly symptoms and induced a significant reduction of GH under the 5 ng/mL limit in microadenoma (P < 0.05), while only 18.2% (2/11) in macroadenoma. Meanwhile, tumor shrinkage occurred in 58.8% (10/17) patients, with 1 case in the microadenoma group. All marked shrinkage (> 25%) occurred in the macroadenoma group. Statistical analysis showed tumor shrinkage caused by LAR was greater in macroadenoma group than that in microadenoma group (P < 0.05). During operation, adenoma was soft in 15 cases, with the exception of 2cases in which the soft rumor was divided by fibrous septa, but all tumor removal was smooth.Conclusions A short term administration of preoperative LAR may induce a significant decrease in GH-secretion level and adenoma volume. Presurgical use of octreotide LAR improves surgical results especially in macroadenomas.

  10. H3 histamine receptor antagonist pitolisant reverses some subchronic disturbances induced by olanzapine in mice

    OpenAIRE

    Dudek, Magdalena; Kuder, Kamil; Kołaczkowski, Marcin; Olczyk, Adrian; Żmudzka, Elżbieta; Rak, Aleksandra; Bednarski, Marek; Pytka, Karolina; Sapa, Jacek; Kieć-Kononowicz, Katarzyna

    2016-01-01

    The use of atypical antipsychotic drugs like olanzapine is associated with side effects such as sedation and depression-like symptoms, especially during the initial period of the use. It is believed that the occurrence of these undesirable effectsis mainly the result of the histamine H1receptors blockade by olanzapine. In addition, use of olanzapine increases the level of triglycerides in the blood, which correlates with growing obesity. The aim of this study was to investigate the influence ...

  11. Serial follow-up of presurgical treatment using pasireotide long-acting release with or without octreotide long-acting release for naïve active acromegaly

    Directory of Open Access Journals (Sweden)

    Jan-Shun Chang

    2016-06-01

    Full Text Available The aim of the present study was to evaluate the serial changes of GH and IGF-1 in seven patients with naïve, active acromegaly following presurgical treatment of the somatostatin analog pasireotide long-acting release (LAR and octreotide LAR. The patients were treated with pasireotide LAR with or without octreotide LAR for two years and underwent transsphenoidal adenomectomy. After treatment with the somatostatin analogs, the surgical cure rate was similar to that in patients who underwent transsphenoidal surgery alone. Diabetes insipidus was not identified in any patients after the operation. Pasireotide LAR was effective on GH as well as IGF-1 suppression and tumor size decreasing when used as the primary therapy. Future large-population studies to investigate the surgical curative rate after presurgical treatment with somatostatin analogs in patients with acromegaly and macroadenomas close to the cavernous sinus are warranted. However, that hyperglycemia developed following pre-surgical treatment with pasireotide should take into consideration.

  12. Use of long-acting reversible contraceptives to reduce the rate of teen pregnancy.

    Science.gov (United States)

    Rome, Ellen

    2015-11-01

    Long-acting reversible contraceptives (LARCs) are safe for use in adolescents and do not rely on compliance or adherence for effectiveness. Continuation rates are higher and pregnancy rates are lower for adolescent users of LARCs compared with short-acting methods such as oral contraceptives. Similarly, repeat pregnancy rates are lower when LARCs are used compared with other forms of contraception. Myths and misconceptions about LARCs and other contraceptives remain a barrier to their use. Health care providers are in a unique position to provide confidential care to adolescents, and should provide education to them about the various contraceptive options, especially LARCs.

  13. Liraglutide, a long-acting GLP-1 mimetic, and its metabolite attenuate inflammation after intracerebral hemorrhage

    DEFF Research Database (Denmark)

    Hou, Jack; Manaenko, Anatol; Hakon, Jakob;

    2012-01-01

    receptor (GLP-1R), mechanisms in the brain remain unclear. We investigated the effect of a long-acting GLP-1 analog, liraglutide, and its truncated metabolite, GLP-1(9-36)a from dipeptidyl peptidase-4 (DPP-4) cleavage in ICH-induced brain injury. Primary outcomes were cerebral edema formation......, neurobehavior, and inflammatory parameters. GLP-1(9-36)a, GLP-1R inhibitor, adenosine monophosphate-activated protein kinase (AMPK) phosphorylation inhibitor and DPP-4 inhibitor were administered to examine the mechanisms of action. Liraglutide suppressed neuroinflammation, prevented brain edema and neurologic...

  14. Increasing Use of Long-Acting Reversible Contraception to Decrease Unplanned Pregnancy.

    Science.gov (United States)

    Lotke, Pamela S

    2015-12-01

    Unintended pregnancy remains high in the United States, accounting for one-half of pregnancies. Both contraceptive nonuse and imperfect use contribute to unplanned pregnancies. Long-acting reversible contraception (LARC) have greater efficacy than shorter acting methods. Data from large studies show that unplanned pregnancy rates are lower among women using LARC. However, overall use of LARC is low; of the reproductive age women using contraception, less than 10% are LARC users. Barriers include lack of knowledge and high up-front cost, and prevent more widespread use. Overcoming these barriers and increasing the number of women using LARC will decrease unplanned pregnancies and abortions.

  15. Characteristics of patients with COPD newly prescribed a long-acting bronchodilator: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Wurst KE

    2014-09-01

    Full Text Available Keele E Wurst,1 Samantha St Laurent,1 Hana Mullerova,2 Kourtney J Davis3 1Worldwide Epidemiology, GlaxoSmithKline R&D, Research Triangle Park, NC, USA; 2Worldwide Epidemiology, GlaxoSmithKline R&D, Uxbridge, UK; 3Worldwide Epidemiology, GlaxoSmithKline R&D, Wavre, Belgium Introduction: This study aimed to characterize patients with chronic obstructive pulmonary disease (COPD newly prescribed a long-acting bronchodilator (LABD, and to assess changes in medication over 24 months. Methods: A cohort of patients with COPD aged ≥40 years newly prescribed an LABD between January 1, 2007 and December 31, 2009 were identified from the Truven Marketscan® Commercial Database (Truven Health Analytics, Ann Arbor, MI, USA and followed for 24 months. Inclusion criteria included no prior prescription for an LABD or inhaled corticosteroids for 12 months prior to the LABD index date (baseline. Patient characteristics were examined. As LABDs were mainly long-acting muscarinic antagonists (LAMAs, additions, switches, discontinuation, adherence to (medication possession ratio, and persistence (proportion of days covered with LAMA monotherapy were assessed for 24 months following the index date. Adherence and persistence with long-acting β2-agonists (LABAs were also assessed. Results: A cohort of 3,268 patients aged 40–65 years was identified (mean age 55.8 years, 48% male. LAMA monotherapy was prescribed to 93% of patients who received an LABD. During the 24-month follow-up, 16% of these patients added COPD medication, 10% switched to an inhaled corticosteroid-containing medication, and 25% discontinued after one LAMA prescription at baseline. Over 12 and 24 months, adherence to LAMA was 40% and 33%, respectively, and adherence to LABA was 29% and 24%, respectively. Over the same time periods, persistence with LAMA monotherapy was 19% and 15%, respectively, and persistence with LABA was 9% and 7%, respectively. Conclusion: Adherence to newly initiated LAMA

  16. Olanzapine versus Placebo in Adolescents with Schizophrenia; a 6-Week, Randomized Double-Blind, Placebo-Controlled Trial

    Science.gov (United States)

    Kryzhanovskaya, Ludmila; Schulz, Charles; McDougle, Christopher; Frazier, Jean; Dittman, Ralf; Robertson-Plouch, Carol; Bauer, Theresa; Xu, Wen; Wang, Wei; Carlson, Janice; Tohen, Mauricio

    2009-01-01

    The efficacy of olanzapine in treating schizophrenia was tested through a placebo-controlled trial involving one hundred seven inpatient and outpatients adolescents. Patients who took olanzapine experienced significant symptom improvement.

  17. DEVELOPMENT AND BIOEQUIVALENCE STUDY OF OLANZAPINE 10mg TABLETS

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    Ravindra Waykar et al

    2012-09-01

    Full Text Available Generic drugs are lower-cost versions of patent-expired original brand-name medications. According to guidelines of regulatory agencies of the Canada, US and European Union, a generic drug must be “identical, or bioequivalent to a brand name drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use”. Bioequivalence is decreed when the ratio of the generic to the reference compound for the area-under-the-curve and maximum plasma concentration (Cmax fall within a 0.80–1.25 range. The present study was to develop Olanzapine Tablets and compare pharmacokinetic profile of Zyprexa 10 mg film-coated tablets, Zyprexa Velotabs 10 mg orodispersible tablets and Olanzapine 10mg tablets. Multi media dissolution studies in 0.1N HCl, pH 4.5 acetate buffer and pH 6.8 phosphate buffer were carried out for Reference (Zyprexa Velotab 10 mg and Zyprexa 10 mg and test product (i.e. Olanzapine 10 mg. A single centre, open-label, single-dose, randomised, 3-way crossover bioequivalence study, performed under fasting conditions. Based on the results obtained, it can be concluded that the test olanzapine (Treatment A is bioequivalent to both references Zyprexa Velotab (Treatment B and Zyprexa (Treatment C following a 10 mg dose under fasting conditions. All formulations were well tolerated, with no major side effects and no relevant differences in safety profiles were observed between the preparations, particularly with respect to the number and pattern of adverse event.

  18. Beta-Adrenergic Receptors and Mechanisms in Asthma: The New Long-Acting Beta-Agonists

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    Robert G Townley

    1996-01-01

    Full Text Available The objective is to review β-adrenergic receptors and mechanisms in the immediate and late bronchial reaction in asthma and the new long-acting β-agonist. This will be discussed in light of the controversy of the potential adverse effect of regular use of long-acting β-agonists. We studied the effect of formoterol on the late asthmatic response (LAR and airway inflammation in guinea-pigs. Formoterol suppressed the LAR, antigen-induced airway inflammation and hyperresponsiveness, although isoproterenol failed to inhibit these parameters. β-Adrenergic hyporesponsiveness, and cholinergic and a- adrenergic hyperresponsiveness have been implicated in the pathogenesis of asthma. A decrease in β-adrenoreceptor function can result either from exogenously administered β-agonist or from exposure to allergens resulting in a late bronchial reaction. There is increasing evidence that eosinophils, macrophages, and lymphocytes which are of primary importance in the late bronchial reaction are also modulated by β2- adrenoreceptors. In functional studies of guinea-pig or human isolated trachea and lung parenchyma, PAF and certain cytokines significantly reduced the potency of isoproterenol to reverse methacholine- or histamine-induced contraction. The effect of glucocorticoids on pulmonary β-adrenergic receptors and responses suggests an important role for glucocorticoids to increase β-adrenergic receptors and responsiveness.

  19. Long-acting β2-adrenergic receptor agonist in pediatric asthma

    Directory of Open Access Journals (Sweden)

    Shigemi Yoshihara

    2004-01-01

    Full Text Available Long-acting β2-adrenergic receptor agonists (LABA, a class of agents for the long-term management of childhood bronchial asthma, are recommended for use in combination with steroid inhalation for the treatment of the morning dip in severe childhood asthma. In the present review, salmeterol (SM, a LABA inhalant with a long-acting bronchodilator effect, was compared with the recently introduced tulobuterol patch (TBP in terms of safety and efficacy, based on their respective clinical effects on childhood asthma. From a clinical perspective, both drugs had a preventive effect by suppressing the morning dip and exercise-induced asthma when used concomitantly with an inhaled corticosteroid, and both agents were associated with a lower incidence of adverse effects on the cardiovascular system than oral β2-adrenergic receptor agonists. Based on these findings, both SM and TBP are concluded to be highly efficacious and safe bronchodilator agents that are appropriate for the long-term management of childhood asthma.

  20. Betahistine ameliorates olanzapine-induced weight gain through modulation of histaminergic, NPY and AMPK pathways.

    Science.gov (United States)

    Lian, Jiamei; Huang, Xu-Feng; Pai, Nagesh; Deng, Chao

    2014-10-01

    Olanzapine is widely used to treat schizophrenia and other disorders, but causes adverse obesity and other metabolic side-effects. Both animal and clinical studies have shown that co-treatment with betahistine (a histaminergic H1 receptor agonist and H3 receptor antagonist) is effective for ameliorating olanzapine-induced weight gain/obesity. To reveal the mechanisms underlying these effects, this study investigated the effects of co-treatment of olanzapine and betahistine (O+B) on expressions of histaminergic H1 receptor (H1R), AMP-activated protein kinase (AMPK), neuropeptide Y (NPY), and proopiomelanocortin (POMC) in the hypothalamus associated with reducing olanzapine-induced weight gain. Olanzapine significantly upregulated the mRNA and protein expressions of H1R, while O+B co-treatment significantly downregulated the H1R levels, compared to the olanzapine-only treatment group. The NPY mRNA expression was significantly enhanced by olanzapine, but it was significantly reversed by O+B co-treatment. The hypothalamic H1R expression was positively correlated with total food intake, and NPY expression. Olanzapine also increased AMPKα activation measured by the AMPKα phosphorylation (pAMPKα)/AMPKα ratio compared with controls, whereas O+B co-treatment decreased the pAMPKα/AMPKα ratio, compared with olanzapine only treatment. The pAMPKα/AMPKα ratio was positively correlated with total food intake and H1R expression. Although olanzapine administration decreased the POMC mRNA level, this level was not affected by O+B co-treatment. Therefore, these results suggested that co-treatment with betahistine may reverse olanzapine-induced body weight gain via the H1R-NPY and H1R-pAMPKα pathways.

  1. Demand for long acting and permanent contraceptive methods and associated factors among family planning service users, Batu town, Central Ethiopia.

    Science.gov (United States)

    Haile, Anley; Fantahun, Mesganaw

    2012-01-01

    Evidence suggests a high unsatisfied demand for long acting and permanent contraceptive methods in sub-Saharan Africa. However, there is limited knowledge on demand for long acting and permanent contraceptive methods and associated factors in Ethiopia. The objective of this study was to assess demand for long acting and permanent contraceptive methods and associated factors among women of age group 18-49 years in Batu town, East Shoa Zone, Ethiopia. A facility based cross-sectional survey was conducted in six service delivery points from March to April 2009 on 398 women of age 18-49 years old. Thirteen (3%) were using long acting and permanent contraceptive methods and 89 (22.4%) wanted no more child in the future making the total demand of long acting and permanent contraceptive methods 24.4%. Older age group, multiparty, that the provider asked about reproductive intention, and the provider explained side effects of method selected were significantly associated with using LA and MPs (P contraceptive methods indicating that multi-dimensional measures are needed to improve the use of long acting and permanent contraceptive methods.

  2. Determination of olanzapine by spectrophotometry using permanganate

    Directory of Open Access Journals (Sweden)

    Nagaraju Rajendraprasad

    2009-09-01

    Full Text Available Two new spectrophotometric methods using permanganate as the oxidimetric reagent for the determination of olanzapine (OLP were developed and validated as per the current ICH guidelines. The methods involved the addition of known excess of permanganate to OLP in either acid or alkaline medium followed by the determination of unreacted permanganate at 550 nm (method A or bluish-green color of manganate at 610 nm (method B. The decrease in absorbance in method A or increase in absorbance in method B as a function of concentration of OLP was measured and related to OLP concentration. Under optimized conditions, Beer's law was obeyed over the ranges 2.0 to 20 and 1.0 to 10 μg mL-1 in method A and method B, respectively. The calculated molar absorptivity values were 1.34 x 10(4 and 2.54 x 10(4 l mol-1cm-1 for method A and method B respectively, and the respective Sandell sensitivities were 0.0233 and 0.0123 μg cm-2. The LOD and LOQ for method A were calculated to be 0.37 and 1.13 μg mL-1and the corresponding values for method B were 0.16 and 0.48 μg mL-1. Intermediate precision, expressed as RSD was in the range 0.51 to 2.66 %, and accuracy, expressed as relative error ranged from 0.79 to 2.24 %. The proposed methods were successfully applied to the assay of OLP in commercial tablets with mean percentage recoveries of 102 ±1.59 % (method A and 101 ±1.53 % (method B. The accuracy and reliability of the methods were further confirmed by performing recovery tests via standard addition procedure.Dois métodos espectrofotométricos novos, usando o permanganato como o reagente oxidimétrico para a determinação da olanzapina (OLP foram utilizados e validados de acordo com as diretrizes atuais do ICH. Os métodos envolveram a adição de excesso conhecido de permanganato à OLP em meio ácido ou alcalino, determinando-se o permanganato que não reagiu em 550 nm (método A, ou pela cor verde-azulada do manganato a 610 nm (método B. A diminuição da

  3. Long acting risperidone in Australian patients with chronic schizophrenia: 24-month data from the e-STAR database

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    Lambert Tim

    2012-03-01

    Full Text Available Abstract Background This observational study was designed to collect treatment outcomes data in patients using the electronic Schizophrenia Treatment Adherence Registry (e-STAR. Methods Patients with schizophrenia or schizoaffective disorder in Australia who were prescribed risperidone long-acting injection (RLAI between 2003 and 2007 were assessed 12-months retrospectively, at baseline and 24-months prospectively at 3-monthly intervals. The intent-to-treat population, defined as all patients who received at least one dose of RLAI at baseline, was used for the efficacy and safety analyses. Results At total of 784 patients (74% with schizophrenia, 69.8% male with a mean age of 37.1 ± 12.5 years and 10.6 ± 9.5 years since diagnosis were included in this Australian cohort. A significant improvement in mean Clinical Global Impression - severity score was observed at 24-months (4.52 ± 1.04 at baseline, 3.56 ± 1.10 at 24-months. Most of this improvement was seen by 3-months and was also reflected in mean Global Assessment of Functioning score, which improved significantly at 24-months (42.9 ± 14.5 at baseline, 59 ± 15.4 at 24-months. For patients still receiving RLAI at 24-months there was an increase from a mean baseline RLAI dose of 26.4 ± 5 mg to 43.4 ± 15.7 mg. Sixty-six percent of patients discontinued RLAI before the 24-month period--this decreased to 46% once patients lost to follow-up were excluded. Conclusion Over the 24-month period, initiation of RLAI was associated with improved patient functioning and illness severity in patients with schizophrenia or schizoaffective disorder. Improved outcomes were observed early and sustained throughout the study. Trial Registration Clinical Trials Registration Number, NCT00283517.

  4. [Olanzapine efficacy in the treatment of cocaine abuse in methadone maintenance patients. Interaction with plasma levels].

    Science.gov (United States)

    Baño, M D; Micó, J A; Agujetas, M; López, M L; Guillén, J L

    2001-01-01

    The aim of this study was to evaluate the efficacy of the treatment with antipsychotic olanzapine in cocaine abuse methadone patients. The decrease or interruption of cocaine consume as well as the possible pharmacokinetic interaction between olanzapine and methadone were studied. Patients (n= 21) include in a methadone maintenance program (14 months), with DSM-IV criteria for opioid and cocaine dependence and without schizophrenic diagnostic, were treated with olanzapine 5 to 10 mg/day. The therapeutic outcomes were assessed by personal interviews, cocaine consumption, changes of consumption patrons (via of administration) and secondary effects to olanzapine. Withdrawal symptoms were measured by means of the abbreviate version of the scale of Gossop. Cocaine used was measured by urine analysis (enzymoimmnuoassay). The possible pharmacokinetic interaction between olanzapine and methadone was measured in plasma before and during the treatment in 15 patients. Olanzapine combined with methadone in cocaine abusers was well tolerated in an important proportion of patients. Moreover the consumption of cocaine was decreased or stopped in 53,2% of the patients. In addition, no withdrawal syndrome was observed in any patients. Furthermore the ratios of methadone plasma levels did not change in relation to the dose before and during the treatment, suggesting a lack of pharmacokinetic interaction between methadone and olanzapine. In conclusion the results of this preliminary study, led us to advance that olanzapine could be a useful treatment for cocaine abuse at least in patients in a Methadone Maintenance Program, with the advantage of not to induce any pharmacokinetic interaction with methadone.

  5. A randomized open-label comparison of the impact of olanzapine versus risperidone on sexual functioning

    NARCIS (Netherlands)

    Knegtering, H; Boks, M; Blijd, C; Castelein, S; Van den Bosch, RJ; Wiersma, D

    2006-01-01

    The objective of this study was to compare sexual functioning in patients treated with olanzapine or risperidone. This open-label trial included 46 patients randomized to olanzapine (5-15mg/d) or risperidone (1-6mg/d) for 6 weeks. We used sexual dysfunction was assessed by a semistructured interview

  6. Levonorgestrel-releasing intrauterine systems for long-acting contraception: current perspectives, safety, and patient counseling

    Directory of Open Access Journals (Sweden)

    Costescu DJ

    2016-10-01

    Full Text Available Dustin J Costescu Department of Obstetrics and Gynaecology, McMaster University, Hamilton, ON, Canada Abstract: Unintended pregnancy is a significant global problem. In 2008, there were over 100 million unplanned pregnancies worldwide, representing approximately 41% of global conceptions. Family planning strategies in many countries are shifting from increasing the uptake of contraception among nonusers to increasing the uptake of the most effective methods among users of less effective methods. One of the most effective and acceptable methods of contraception is the levonorgestrel-releasing intrauterine system (LNG IUS; however, its uptake varies widely by country. This article reviews the currently available LNG IUSs, the rationale for increasing uptake of these methods, and evidence regarding safety, and discusses counseling strategies to best inform women about this option for contraception. Keywords: LNG IUS, long-acting contraception, intrauterine contraception, levonorgestrel, contraception, family planning

  7. Shared Decision Aids: Increasing Patient Acceptance of Long-Acting Reversible Contraception

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    Tracy P. George

    2015-04-01

    Full Text Available Unintended pregnancies are an important public health issue. Long-acting reversible contraceptive methods (LARCs are reliable, safe, highly effective methods for most women; however they are underutilized in the United States. Shared decision aids were added to usual care in five public health family planning clinics in the Southeastern United States, staffed by advance practice nurses and registered nurses. All five sites showed an increase in the use of LARCs during the time period that shared decision aids were used (results statistically significant to p < 0.001. It is important for women to make informed choices about contraception, and shared decision aids can be utilized to support this decision making. This resource has been adopted for statewide use in all public health clinics, and implications for practice suggest that the use of shared decision aids is an effective method to support informed patient decision making and acceptance of LARC methods of contraception.

  8. Effect of long-acting beta2 agonists on exacerbation rates of asthma in children

    DEFF Research Database (Denmark)

    Bisgaard, Hans

    2003-01-01

    The purpose of this analysis was to examine the effect of long-acting beta(2)-adrenoceptor agonists (LABAs) on the asthma exacerbation rate in pediatric patients. Randomized controlled trials (RCT) that included the use of LABAs to treat symptoms of pediatric asthma in children on inhaled...... requiring a change in prescribed medication or not defined but reported as an asthma exacerbation or an asthma-related hospitalization. Analysis of data from the eight studies revealed no apparent protection from an asthma exacerbation among children on a LABA compared to patients on comparator treatment...... that reported asthma-related hospitalizations. The lack of evidence for the control of asthma exacerbations in children regularly using a LABA should bring into question its general use as add-on therapy. Studies should be designed to directly explore the implications of these observations in pediatric patients....

  9. Characteristics of physicians who frequently prescribe long-acting benzodiazepines for the elderly.

    Science.gov (United States)

    Monette, J; Tamblyn, R M; McLeod, P J; Gayton, D C

    1997-06-01

    Long-acting benzodiazepines (LABZs) are relatively contraindicated for elderly patients because they increase the risk of impaired cognitive function, falls, and hip fractures. The purpose of this study was to identify the characteristics of physicians who frequently prescribe LABZs for elderly patients. The authors examined the prescribing profile of 4,976 physicians who saw at least 20 elderly Quebec medicare registrants in 1990. Physicians who frequently prescribed LABZs for their elderly patients were more likely to have graduated before 1979, to be general practitioners as opposed to specialists, to practice in long-term care settings, and to have graduated from a medical school in Quebec as opposed to other schools in Quebec, in other provinces, or in other countries. The authors have identified several characteristics of physicians who frequently prescribed LABZs for the elderly. Strategies to improve prescribing in this field should target this group of physicians.

  10. Long-Acting Muscarinic Antagonists for Difficult-to-Treat Asthma: Emerging Evidence and Future Directions.

    Science.gov (United States)

    Bulkhi, Adeeb; Tabatabaian, Farnaz; Casale, Thomas B

    2016-07-01

    Asthma is a complex disease where many patients remain symptomatic despite guideline-directed therapy. This suggests an unmet need for alternative treatment approaches. Understanding the physiological role of muscarinic receptors and the parasympathetic nervous system in the respiratory tract will provide a foundation of alternative therapeutics in asthma. Currently, several long-acting muscarinic antagonists (LAMAs) are on the market for the treatment of respiratory diseases. Many studies have shown the effectiveness of tiotropium, a LAMA, as add-on therapy in uncontrolled asthma. These studies led to FDA approval for tiotropium use in asthma. In this review, we discuss how the neurotransmitter acetylcholine itself contributes to inflammation, bronchoconstriction, and remodeling in asthma. We further describe the current clinical studies evaluating LAMAs in adult and adolescent patients with asthma, providing a comprehensive review of the current known physiological benefits of LAMAs in respiratory disease.

  11. Side effects of pharmacotherapy on bone with long-acting gonadorelin agonist triptorelin for paraphilia.

    Science.gov (United States)

    Hoogeveen, John; Van der Veer, Eveline

    2008-03-01

    There have been limited research studies concerning the use of libido inhibitors for the treatment of patients with a paraphilia. Observational studies suggest that agents that lower testosterone are an effective treatment for paraphilia. We report a case of hormonal treatment of paraphilia that was associated with side effects. A 35-year-old man with a paraphilia was treated with long-acting gonadorelin. The desired result was reduced preoccupation with sexuality, but there were various side effects including a serious amount of bone loss. We believe that more attention should be given to the adverse effects of long-term treatment with triptorelin. In our view the drug regime needs to be revised.

  12. Barriers and Facilitators to Adolescents' Use of Long-Acting Reversible Contraceptives.

    Science.gov (United States)

    Pritt, Nicole M; Norris, Alison H; Berlan, Elise D

    2017-02-01

    Most pregnancies among teenagers are unintended and many can be attributed to contraception misuse or nonuse. The etonogestrel implant and intrauterine devices, referred to as long-acting reversible contraceptives, or LARCs, are the most effective reversible contraceptive methods. These methods are safe for use by adolescents, yet the number of LARC users remains low among adolescents in the United States. In this review we examine recent literature about barriers and facilitators to LARC use among adolescent women. Factors that influence decision-making and provision are organized into 4 categories: (1) cost and clinical operations; (2) adolescent awareness and attitudes; (3) confidentiality, consent, and parental attitudes; and (4) health care provider knowledge, attitudes, and counseling. Knowledge deficits and misconceptions among adolescents and their health care providers are key barriers to adolescent LARC use. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  13. A pediatric non-protein losing Menetrier's disease successfully treated with octreotide long acting release

    Institute of Scientific and Technical Information of China (English)

    Giovanni Di Nardo; Salvatore Oliva; Marina Aloi; Federica Ferrari; Simone Frediani; Adriana Marcheggiano; Salvatore Cucchiara

    2012-01-01

    Pediatric Menetrier's disease (MD) is an uncommon,acute,self-limited hypertrophic gastropathy characterized by enlarged gastric folds associated with epithelial hyperplasia and usually accompanied by protein losing gastropathy.Gastric cytomegalovirus infection is found in one third of MD children and its treatment is often associated with remission.Diagnosis often requires fullthickness biopsy due to inability to detect typical histological findings with conventional endoscopic biopsy.We report an uncommon case of non self-limited pediatric MD needing endoscopic mucosal resection for diagnosis which was then successfully treated with octreotide long-acting release (LAR).To the best of our knowledge,this is the first pediatric MD case successfully treated with octreotide LAR.Our experience suggests octreotide LAR as treatment for refractory MD before gastrectomy.

  14. Degludec, a new ultra-long-acting basal insulin for the treatment of diabetes mellitus type 1 and 2: advances in clinical research.

    Science.gov (United States)

    Muñoz Torres, Manuel

    2014-03-01

    Degludec is the most recent molecule of the ultra-long-acting basal insulin analogues approved for human use. It forms soluble multihexamers which after subcutaneous injection are converted into monomers, and are thus slowly and continuously absorbed into the bloodstream. This absorption mechanism confers degludec an ultra-long and stable action profile, with no concentration peaks. This paper discusses the most recent studies in patients with type 1 and 2 diabetes mellitus, which showed degludec to be non inferior in decreasing HbA1c, ensuring optimum glycemic control similar to that achieved with insulin glargine or detemir. Degludec also had an improved safety profile, as it was associated to a significantly lower rate of nocturnal hypoglycemia in both types of diabetes and to a potentially lower overall hypoglycemia rate in type 2 DM. Degludec also opens the possibility to use more flexible regimens.

  15. Long acting β2-agonist and corticosteroid restore airway glandular cell function altered by bacterial supernatant

    Directory of Open Access Journals (Sweden)

    Nawrocki-Raby Béatrice

    2010-01-01

    Full Text Available Abstract Background Staphylococcus aureus releases virulence factors (VF that may impair the innate protective functions of airway cells. The aim of this study was to determine whether a long-acting β2 adrenergic receptor agonist (salmeterol hydroxynaphthoate, Sal combined with a corticosteroid (fluticasone propionate, FP was able to regulate ion content and cytokine expression by airway glandular cells after exposure to S. aureus supernatant. Methods A human airway glandular cell line was incubated with S. aureus supernatant for 1 h and then treated with the combination Sal/FP for 4 h. The expression of actin and CFTR proteins was analyzed by immunofluorescence. Videomicroscopy was used to evaluate chloride secretion and X-ray microanalysis to measure the intracellular ion and water content. The pro-inflammatory cytokine expression was assessed by RT-PCR and ELISA. Results When the cells were incubated with S. aureus supernatant and then with Sal/FP, the cellular localisation of CFTR was apical compared to the cytoplasmic localisation in cells incubated with S. aureus supernatant alone. The incubation of airway epithelial cells with S. aureus supernatant reduced by 66% the chloride efflux that was fully restored by Sal/FP treatment. We also observed that Sal/FP treatment induced the restoration of ion (Cl and S and water content within the intracellular secretory granules of airway glandular cells and reduced the bacterial supernatant-dependent increase of pro-inflammatory cytokines IL8 and TNFα. Conclusions Our results demonstrate that treatment with the combination of a corticosteroid and a long-acting β2 adrenergic receptor agonist after bacterial infection restores the airway glandular cell function. Abnormal mucus induced by defective ion transport during pulmonary infection could benefit from treatment with a combination of β2 adrenergic receptor agonist and glucocorticoid.

  16. The antipsychotic olanzapine interacts with the gut microbiome to cause weight gain in mouse.

    Directory of Open Access Journals (Sweden)

    Andrew P Morgan

    Full Text Available The second-generation antipsychotic olanzapine is effective in reducing psychotic symptoms but can cause extreme weight gain in human patients. We investigated the role of the gut microbiota in this adverse drug effect using a mouse model. First, we used germ-free C57BL/6J mice to demonstrate that gut bacteria are necessary and sufficient for weight gain caused by oral delivery of olanzapine. Second, we surveyed fecal microbiota before, during, and after treatment and found that olanzapine potentiated a shift towards an "obesogenic" bacterial profile. Finally, we demonstrated that olanzapine has antimicrobial activity in vitro against resident enteric bacterial strains. These results collectively provide strong evidence for a mechanism underlying olanzapine-induced weight gain in mouse and a hypothesis for clinical translation in human patients.

  17. Effect of olanzapine treatment on INR of a patient receiving warfarin therapy

    Directory of Open Access Journals (Sweden)

    Derya Arslan

    2016-06-01

    Full Text Available Olanzapine is an atypical antipsychotic drug, commonly used in the management of psychotic symptoms in patients with schizoprenia and bipolar affective disorder. Deep venous thrombosis is a manifestation of venous thromboembolism. It is very well known that use of antipsychotic drugs increase the risk of thrombosis in a patient with schizophrenia. It has been reported in many studies the effects of olanzapine on thrombosis but there isn't any report about the effect of olanzapine on international normalized ratio (INR. in the medical literature. In this paper, a patient with schizophrenia and also family history of deep venous thrombosis who emerged deep venous thrombosis after being started on olanzapine treatment and effect of olanzapine treatment on INR has been reported. [Cukurova Med J 2016; 41(2.000: 370-373

  18. Chronic treatment with long-acting bromocriptine does not affect duration of the breeding season, voluntary food intake, body weight, or wool growth in the Scottish blackface ewe.

    Science.gov (United States)

    Curlewis, J D; Sibbald, A M; Milne, J A; McNeilly, A S

    1991-01-01

    The aim of this study was to determine whether suppression of the seasonal increase in prolactin concentrations by chronic treatment with the dopamine agonist bromocriptine would affect onset of anoestrus, voluntary food intake, body weight, and wool growth in a seasonal breed of sheep. Groups of eight Scottish Blackface ewes were injected i.m. each week with either the vehicle (Group A) or 2.0 mg (Group B), 6.0 mg (Group C), or 18.0 mg (Group D) of bromocriptine in a long-acting formulation, commencing on 18 January and terminating on 25 July (midwinter to midsummer in the northern hemisphere). Immediately before the bromocriptine injection, blood samples were taken for progesterone and prolactin determination. Voluntary food intakes were measured daily, and body weights were recorded every fortnight. Estimates of wool growth were made by weighing wool clipped from a measured area of skin once a month. Treatment had no effect on onset of anoestrus, voluntary food intake, body weight, or wool growth. Plasma prolactin concentrations increased significantly in all groups during the treatment period. From January to April, all doses of bromocriptine significantly reduced prolactin concentrations but later in the study (May and June) prolactin was significantly suppressed in Group D only, although even in this group prolactin concentrations increased between March and June. Pituitary prolactin content, measured at the end of the study in July, was also suppressed by bromocriptine. The gradual increase in prolactin concentrations in ewes receiving chronic bromocriptine was further investigated by treating a fifth group of ewes (Group E) with 18.0 mg of long-acting bromocriptine each week, commencing on 20 June.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Effects of olanzapine on regional C-Fos expression in rat forebrain.

    Science.gov (United States)

    Robertson, G S; Fibiger, H C

    1996-02-01

    Compared to typical antipsychotic drugs, clozapine produces a unique pattern of Fos-like immunoreactive neurons in the rat forebrain. It has been proposed, therefore, that this approach may be useful in identifying other agents with clozapine's therapeutic profile. In the present study, we examined the ability of olanzapine to increase the number of Fos-like immunoreactive neurons in the striatum, nucleus accumbens, lateral septal nucleus, and prefrontal cortex. Olanzapine (5, 10 mg/kg) produced dose-dependent increases in the number of Fos-positive neurons in the nucleus accumbens and lateral septal nucleus, important components of the limbic system that may mediate some of the therapeutic actions of neuroleptics. Olanzapine also produced dose-dependent increases in the number of Fos-positive neurons in the dorsolateral striatum, an effect that correlates with the ability of neuroleptics to produce extrapyramidal side-effects. The effects of olanzapine on regional c-fos expression are not therefore identical to clozapine, which is without effect in the dorsolateral striatum. However, olanzapine-induced increases in the dorsolateral striatum were considerably smaller than those generated in the nucleus accumbens suggesting that at low, potentially therapeutic doses olanzapine may not generate significant extrapyramidal side effects. Olanzapine also increased the number of Fos-positive neurons in medical prefrontal cortex, an action unique to clozapine and a few other atypical antipsychotics. These findings are consistent with the hypothesis that olanzapine is an atypical antipsychotic in the sense that it does not produce significant extrapyramidal side-effects at low therapeutic doses. However, extrapyramidal side-effects at higher doses can be predicted by these results. Finally, olanzapine's actions in the medial prefrontal cortex may be predictive of a clozapine-like profile with respect to actions on negative symptoms in schizophrenia. Additional clinical

  20. Role of indacaterol and the newer very long-acting β2-agonists in patients with stable COPD: a review

    Directory of Open Access Journals (Sweden)

    Ridolo E

    2013-09-01

    Full Text Available Erminia Ridolo,1 Marcello Montagni,1 Elisa Olivieri,1 Gian Galeazzo Riario-Sforza,2 Cristoforo Incorvaia2 1Department of Clinical and Experimental Medicine, University of Parma, Parma, 2Pulmonary Rehabilitation Unit, ICP Hospital, Milan, Italy Abstract: Bronchodilators are central drugs in the management of patients with chronic obstructive pulmonary disease (COPD. Indacaterol was the first agent of the novel family of very long-acting β2-agonists to be used as an inhaled bronchodilator for COPD and provides 24-hour therapeutic action, thus allowing once-daily administration. Data from clinical trials show that indacaterol has a bronchodilator effect similar to that of the anticholinergic tiotropium bromide and slightly higher efficacy compared with the long-acting β2-agonists, salmeterol and formoterol. Moreover, the safety profile is excellent and comparable with that of placebo. Concerning adherence with drug treatment and real-life management in respect to long-acting β2-agonists, once-daily dosing makes indacaterol more convenient for COPD patients and is likely to enhance patient adherence. Other very long-acting β2-agonists currently in development include vilanterol, olodaterol, and carmoterol, and these have shown good characteristics for clinical use in the studies reported thus far. Keywords: chronic obstructive pulmonary disease, bronchodilators, very long-acting β2-agonists

  1. Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analog liraglutide (NN2211): a 12-week, double-blind, randomized, controlled trial

    DEFF Research Database (Denmark)

    Madsbad, Sten; Schmitz, Ole; Ranstam, Jonas;

    2004-01-01

    OBJECTIVE: Liraglutide is a long-acting glucagon-like peptide 1 analog designed for once daily injection. This study assessed the efficacy and safety of liraglutide after 12 weeks of treatment in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A double-blind, randomized, parallel...

  2. Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analog liraglutide (NN2211): a 12-week, double-blind, randomized, controlled trial

    DEFF Research Database (Denmark)

    Madsbad, Sten; Schmitz, Ole; Ranstam, Jonas

    2004-01-01

    OBJECTIVE: Liraglutide is a long-acting glucagon-like peptide 1 analog designed for once daily injection. This study assessed the efficacy and safety of liraglutide after 12 weeks of treatment in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A double-blind, randomized, parallel...

  3. “Set it and forget it”: Women’s perceptions and opinions of long-acting topical vaginal gels

    Science.gov (United States)

    van den Berg, Jacob J.; Rosen, Rochelle K.; Bregman, Dana E.; Thompson, Lara A.; Jensen, Kathleen M.; Kiser, Patrick F.; Katz, David F.; Buckheit, Karen; Buckheit, Robert W.; Morrow, Kathleen M.

    2014-01-01

    Women’s initial understandings and anticipated acceptability of long-acting vaginal gels as potential anti-HIV microbicides was investigated by exploring the perceptibility variables associated with prototype formulations. Four focus groups with 29 women, aged 18–45, were conducted to consider gel prototypes with varied physicochemical and rheological properties. Participants responded favorably to the concept of long-acting vaginal gels as microbicides. Distinctions in understandings and stated needs regarding product dosing, characteristics, and effectiveness offer valuable insights into product design. Long-acting vaginal gels capable of protecting against HIV/STIs will be a viable option among potential users, with dosing frequency being an important factor in willingness to use. PMID:24248674

  4. Association between long-acting reversible contraceptive use, teenage pregnancy, and abortion rates in England

    Directory of Open Access Journals (Sweden)

    Connolly A

    2014-11-01

    Full Text Available Anne Connolly,1 Guilhem Pietri,2 Jingbo Yu,3 Samantha Humphreys4 1The Ridge Medical Practice, Cousen Road, Bradford, UK; 2HERON – A PAREXEL® Company, London, UK; 3Merck & Co, Inc., Whitehouse Station, NJ, USA; 4Merck Sharp & Dohme Limited, Hertfordshire, UK Background: Since the late 1990s, the British government has launched major strategies to address high teenage pregnancy and abortion rates in England. These have focused in part on improving access to contraception through national campaigns. This study assessed teenage pregnancy and abortion rate trends since 1998 and possible associations with usage of long-acting reversible contraceptives (LARCs. Methods: Teenage conception rates and age-specific abortion rates were obtained from the Office for National Statistics and the Department of Health. LARC usage data was obtained for Depo-Provera, Implanon/Nexplanon, intrauterine devices, Mirena, and Noristerat from the IMS British Pharmaceutical Index, IMS Hospital Pharmacy Audit, IMS Disease Analyzer, and KT-31 reports. Through linear regression methods, changes in conception and abortion-related outcomes during 1998–2011 and the associations with LARC usage were assessed. Results: Conception rates for girls younger than 18 years of age decreased significantly between 1998–2011, from 46.6 to 30.7 per 1,000 girls. A statistically significant association was observed between this decrease and increased LARC usage (P=0.0024 in this population. Abortion rates among females aged <18 years or aged 18–19 years decreased between 1998–2011, and their associations with increased LARC usage were statistically significant (P=0.0029 and P=0.0479, respectively. The pattern in older women was complex; abortion rates in women aged 20–24 years or 25–34 years increased slightly from 1998 to 2011, with stabilization during 2007–2011. Conclusion: Increased LARC usage in England was significantly associated with decreased teenage pregnancy rates

  5. Differential pharmacology and clinical utility of long-acting bronchodilators in COPD – focus on olodaterol

    Directory of Open Access Journals (Sweden)

    Matera MG

    2015-12-01

    Full Text Available Maria Gabriella Matera,1 Josuel Ora,2 Mario Cazzola2,3 1Department of Experimental Medicine, Unit of Pharmacology, Second University of Naples, Naples, 2Division of Respiratory Medicine, University Hospital Tor Vergata, 3Department of Systems Medicine, Respiratory Pharmacology Research Unit, University of Rome Tor Vergata, Rome, Italy Abstract: Olodaterol (BI 1744 CL is a novel, once-daily long-acting β2-agonist (LABA designed with the aim of improving β2-adrenoreceptor selectivity and intrinsic activity. Phase III pivotal trials have documented that olodaterol Respimat Soft Mist inhaler 5 µg induces fast onset of bronchodilation, comparable with formoterol at day 1. Moreover, significant lung function improvements have been documented up to 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease (COPD. Olodaterol was generally well tolerated and had an acceptable cardiovascular and respiratory adverse event profile. Regrettably, the clinical development of olodaterol is however still too partial to draw any firm conclusions on the positioning of this ultra-LABA as monotherapy in the management of COPD. Waiting for further data on the impact of olodaterol on different patient-reported outcomes, which however are widely available for indacaterol, and mainly for a head-to-head comparison between these two ultra-LABAs and between olodaterol long-acting antimuscarinic antagonists other than tiotropium, we believe it is correct to follow the clinical indications of indacaterol also for olodaterol. In any case, the parallel bronchodilating modes of action of olodaterol and tiotropium make them an attractive combination in COPD. The results from the ongoing large TOviTO Phase III trial program have documented the efficacy and safety of olodaterol/tiotropium fixed-dose combination as maintenance therapy in patients with moderate to very severe COPD. In particular, olodaterol/tiotropium fixed-dose combination provides

  6. Olanzapine for the treatment of bipolar disorder in children and adolescents.

    Science.gov (United States)

    Strawn, Jeffrey R; Delbello, Melissa P

    2008-02-01

    The second-generation antipsychotic olanzapine has been shown to be efficacious as a treatment for adults with bipolar disorder and is approved by the United States Food and Drug Administration for the treatment of acute manic or mixed episodes as well as for maintenance treatment in bipolar adults. This review examines the use of olanzapine for the treatment of children and adolescents with bipolar disorder and presents a discussion of the mechanism of action, pharmacokinetic and pharmacodynamic properties of olanzapine in children and adolescents. In addition, efficacy and safety data are reviewed and the risks and benefits of using olanzapine in bipolar youth are summarized. Articles published in English were identified using a search of the National Library of Medicine from 1990 to 2007 with manual review of references of each article as well as review of the US Clinical Trials database. Articles describing the use of olanzapine in children or adolescents were included. Olanzapine appears to have a rapid onset of action for mixed and manic episodes, but is associated with metabolic side effects including hyperprolactinemia, diabetes and weight gain. Therefore, olanzapine may best be used in the acute treatment of children and adolescents experiencing a manic or mixed episode as its side-effect profile may limit its use as a maintenance agent in this population.

  7. Effects of intracerebroventricular (ICV) olanzapine on insulin sensitivity and secretion in vivo: an animal model.

    Science.gov (United States)

    Hahn, Margaret K; Chintoh, Araba; Remington, Gary; Teo, Celine; Mann, Steve; Arenovich, Tamara; Fletcher, Paul; Lam, Loretta; Nobrega, Jose; Guenette, Melanie; Cohn, Tony; Giacca, Adria

    2014-03-01

    The atypical antipsychotics (AAPs) have been associated with an increased risk of type 2 diabetes. While weight gain associated with AAPs is a risk factor for diabetes, preclinical work suggests that among these medications, olanzapine, when given peripherally in a single dose, causes pronounced effects on insulin sensitivity and secretion. Given a critical role of the hypothalamus in control of glucose metabolism, we examined the effect of central administration of olanzapine. Sprague-Dawley rats were treated with a single 75 μg intracerebroventricular (ICV) dose of olanzapine and tested using separate hyperinsulinemic-euglycemic and hyperglycemic clamps. Dosing of olanzapine was established based on inhibition of amphetamine-induced locomotion. In contrast to the single dosing peripheral paradigm, there was no effect of central olanzapine on insulin sensitivity, either with respect to hepatic glucose production or peripheral glucose uptake. Analogous to the peripheral model, a single ICV dose of olanzapine followed by the hyperglycemic clamp decreased insulin (p=0.0041) and C-peptide response (p=0.0039) to glucose challenge as compared to vehicle, mirrored also by a decrease in the steady state glucose infusion rate required to maintain hyperglycemia (p=0.002). In conclusion, we demonstrate novel findings that at least part of the effect of olanzapine on beta-cell function in vivo is central.

  8. Amantadine for weight gain associated with olanzapine treatment.

    Science.gov (United States)

    Deberdt, Walter; Winokur, Andrew; Cavazzoni, Patrizia A; Trzaskoma, Quynh N; Carlson, Christopher D; Bymaster, Frank P; Wiener, Karen; Floris, Michel; Breier, Alan

    2005-01-01

    Patients with schizophrenia (Sch), schizoaffective, schizophreniform, or bipolar (BP) I disorders [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)]; not manic or acutely psychotic [Brief Psychiatric Rating Scale (BPRS) total score or =5% of their initial body weight were examined to determine whether amantadine could attenuate weight gain or promote weight loss. Olanzapine (Olz; 5-20 mg/day) was co-administered with double-blind treatment of 100-300 mg/day amantadine (Olz+Amt, n=60) or placebo (Olz+Plc, n=65). Visit-wise analysis of weight showed that weight change from baseline [last-observation-carried-forward (LOCF)] in the Olz+Amt group was significantly different from the Olz+Plc group at weeks 8 (P=0.042), 12 (P=0.029), and 16 (primary endpoint, mean+/-S.D.: -0.19+/-4.58 versus 1.28+/-4.26 kg, P=0.045). Mean BPRS total score, positive subscale, and anxiety-depression scores improved comparably in both groups, and Montgomery-Asberg Depression Rating Scale (MADRS) total score improved in the Olz+Amt group. Overall, amantadine was safe, was well tolerated, and attenuated weight gain or promoted weight loss in some patients who had gained weight during olanzapine therapy.

  9. How can lipid nanocarriers improve transdermal delivery of olanzapine?

    Science.gov (United States)

    Iqbal, Nimra; Vitorino, Carla; Taylor, Kevin M G

    2017-06-01

    The development of a transdermal nanocarrier drug delivery system with potential for the treatment of psychiatric disorders, such as schizophrenia and bipolar disorder, is described. Lipid nanocarriers (LN), encompassing various solid:liquid lipid compositions were formulated and assessed as potential nanosystems for transdermal delivery of olanzapine. A previously optimized method of hot high pressure homogenization (HPH) was adopted for the production of the LN, which comprised solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE). Precirol( ®) was selected as the solid lipid for progression of studies. SLN exhibited the best performance for transdermal delivery of olanzapine, based on in vitro release and permeation studies, coupled with results from physicochemical characterization of several solid:liquid lipid formulations. Stability tests, performed to give an indication of long-term storage behavior of the formulations, were in good agreement with previous studies for the best choice of solid:liquid lipid ratio. Overall, these findings highlight the SLN-based formulation as promising for the further inclusion in and production of transdermal patches, representing an innovative therapeutic approach.

  10. Role of indacaterol and the newer very long-acting β2-agonists in patients with stable COPD: a review

    Science.gov (United States)

    Ridolo, Erminia; Montagni, Marcello; Olivieri, Elisa; Riario-Sforza, Gian Galeazzo; Incorvaia, Cristoforo

    2013-01-01

    Bronchodilators are central drugs in the management of patients with chronic obstructive pulmonary disease (COPD). Indacaterol was the first agent of the novel family of very long-acting β2-agonists to be used as an inhaled bronchodilator for COPD and provides 24-hour therapeutic action, thus allowing once-daily administration. Data from clinical trials show that indacaterol has a bronchodilator effect similar to that of the anticholinergic tiotropium bromide and slightly higher efficacy compared with the long-acting β2-agonists, salmeterol and formoterol. Moreover, the safety profile is excellent and comparable with that of placebo. Concerning adherence with drug treatment and real-life management in respect to long-acting β2-agonists, once-daily dosing makes indacaterol more convenient for COPD patients and is likely to enhance patient adherence. Other very long-acting β2-agonists currently in development include vilanterol, olodaterol, and carmoterol, and these have shown good characteristics for clinical use in the studies reported thus far. PMID:24082783

  11. Conversion of daily pegvisomant to weekly pegvisomant combined with long-acting somatostatin analogs, in controlled acromegaly patients

    NARCIS (Netherlands)

    S.J.C.M.M. Neggers (Bas); W.W. de Herder (Wouter); R.A. Feelders (Richard); A-J. van der Lely (Aart-Jan)

    2011-01-01

    textabstractThe efficacy of combined treatment in active acromegaly with both long-acting somatostatin analogs (SRIF) and pegvisomant (PEG-V) has been well established. The aim was to describe the PEG-V dose reductions after the conversion from daily PEG-V to combination treatment. To clarify the in

  12. Antidote strategies to reverse anticoagulation with TB-402, a long-acting partial inhibitor of factor VIII

    NARCIS (Netherlands)

    Tangelder, M.; Long, C.; Emmerechts, J.; Jacquemin, M.; Peerlinck, K.; Vanassche, T.; Glazer, S.; Giesen, P.; Hoylaerts, M.; Verhamme, P.

    2012-01-01

    . Background: TB-402 is a partially inhibiting antibody of factor VIII that is under development as a long-acting anticoagulant. Patients and Methods: The reversibility of FVIII inhibition by TB-402 was evaluated in vitro after spiking with recombinant human FVIII (rhFVIII), human plasma-derived FVI

  13. Conversion of daily pegvisomant to weekly pegvisomant combined with long-acting somatostatin analogs, in controlled acromegaly patients

    NARCIS (Netherlands)

    S.J.C.M.M. Neggers (Bas); W.W. de Herder (Wouter); R.A. Feelders (Richard); A-J. van der Lely (Aart-Jan)

    2011-01-01

    textabstractThe efficacy of combined treatment in active acromegaly with both long-acting somatostatin analogs (SRIF) and pegvisomant (PEG-V) has been well established. The aim was to describe the PEG-V dose reductions after the conversion from daily PEG-V to combination treatment. To clarify the

  14. [Effect of barnidipine hydrochloride on the autonomic nervous system: difference between short- and long-acting components of calcium antagonist].

    Science.gov (United States)

    Soejima, K; Akaishi, M; Oyamada, K; Mitamura, H; Ogawa, S

    1997-07-01

    Short-acting calcium antagonists have a deleterious effect on the prognosis for patients with myocardial ischemia, possibly caused by overactivation of sympathetic nerves due to vasodilatation, negative inotropism, or coronary steal. However, there is considerable debate about whether long-acting calcium antagonists as well as the short-acting calcium antagonists have the same effect. Barnidipine-HCl is a newly-developed calcium antagonist with 1:2 short- and long-acting particles. This study evaluated the changes of autonomic tone due to barnidipine. Both the short- and long-acting effect of the calcium antagonist was evaluated. Eleven patients with primary hypertension underwent 24-hour ambulatory electrocardiogram and blood pressure monitoring before and after the treatment with barnidipine. Heart rate and blood pressure were compared before and after the medication. Heart rate variability was analyzed with a Marquette 8000/T. High frequency power (HF), as a parameter of vagal tone, and the ratio to low frequency power (LF), as a parameter of sympathetic tone, were obtained. Twenty-four-hour average blood pressure decreased significantly during the day, but nocturnal hypotension was not observed. Heart rate did not increase. HF decreased at the peak of the short- and long-acting components. LF/HF increased at the peak of the short-acting component. Short-acting particles of barnidipine had a deleterious effect on the autonomic tone, that is overactivation of sympathetic tone and suppression of vagal tone. Long-acting particles of barnidipine suppressed the vagal tone. These findings suggest that short-acting calcium antagonists may cause arrhythmia or deterioration of coronary ischemia.

  15. Pharmacokinetics of long-acting tenofovir alafenamide (GS-7340) subdermal implant for HIV prophylaxis.

    Science.gov (United States)

    Gunawardana, Manjula; Remedios-Chan, Mariana; Miller, Christine S; Fanter, Rob; Yang, Flora; Marzinke, Mark A; Hendrix, Craig W; Beliveau, Martin; Moss, John A; Smith, Thomas J; Baum, Marc M

    2015-07-01

    Oral or topical daily administration of antiretroviral (ARV) drugs to HIV-1-negative individuals in vulnerable populations is a promising strategy for HIV-1 prevention. Adherence to the dosing regimen has emerged as a critical factor determining efficacy outcomes of clinical trials. Because adherence to therapy is inversely related to the dosing period, sustained release or long-acting ARV formulations hold significant promise for increasing the effectiveness of HIV-1 preexposure prophylaxis (PrEP) by reducing dosing frequency. A novel, subdermal implant delivering the potent prodrug tenofovir alafenamide (TAF) with controlled, sustained, zero-order (linear) release characteristics is described. A candidate device delivering TAF at 0.92 mg day(-1) in vitro was evaluated in beagle dogs over 40 days for pharmacokinetics and preliminary safety. No adverse events related to treatment with the test article were noted during the course of the study, and no significant, unusual abnormalities were observed. The implant maintained a low systemic exposure to TAF (median, 0.85 ng ml(-1); interquartile range [IQR], 0.60 to 1.50 ng ml(-1)) and tenofovir (TFV; median, 15.0 ng ml(-1); IQR, 8.8 to 23.3 ng ml(-1)), the product of in vivo TAF hydrolysis. High concentrations (median, 512 fmol/10(6) cells over the first 35 days) of the pharmacologically active metabolite, TFV diphosphate, were observed in peripheral blood mononuclear cells at levels over 30 times higher than those associated with HIV-1 PrEP efficacy in humans. Our report on the first sustained-release nucleoside reverse transcriptase inhibitor (NRTI) for systemic delivery demonstrates a successful proof of principle and holds significant promise as a candidate for HIV-1 prophylaxis in vulnerable populations. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  16. Long-acting glucose-dependent insulinotropic polypeptide ameliorates obesity-induced adipose tissue inflammation.

    Science.gov (United States)

    Varol, Chen; Zvibel, Isabel; Spektor, Lior; Mantelmacher, Fernanda Dana; Vugman, Milena; Thurm, Tamar; Khatib, Marian; Elmaliah, Elinor; Halpern, Zamir; Fishman, Sigal

    2014-10-15

    Obesity induces low-grade chronic inflammation, manifested by proinflammatory polarization of adipose tissue innate and adaptive resident and recruited immune cells that contribute to insulin resistance (IR). The glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that mediates postprandial insulin secretion and has anabolic effects on the adipose tissue. Importantly, recent evidence suggested that GIP is a potential suppressor of inflammation in several metabolic models. In this study, we aimed to investigate the immunoregulatory role of GIP in a murine model of diet-induced obesity (DIO) using the long-acting GIP analog [d-Ala(2)]GIP. Administration of [d-Ala(2)]GIP resulted in adipocytes of increased size, increased levels of adipose tissue lipid droplet proteins, indicating better lipid storage capacity, and reduced adipose tissue inflammation. Flow cytometry analysis revealed reduced numbers of inflammatory Ly6C(hi) monocytes and F4/80(hi)CD11c(+) macrophages, associated with IR. In addition, [d-Ala(2)]GIP reduced adipose tissue infiltration of IFN-γ-producing CD8(+) and CD4(+) T cells. Furthermore, [d-Ala(2)]GIP treatment induced a favorable adipose tissue adipokine profile, manifested by a prominent reduction in key inflammatory cytokines (TNF-α, IL-1β, IFN-γ) and chemokines (CCL2, CCL8, and CCL5) and an increase in adiponectin. Notably, [d-Ala(2)]GIP also reduced the numbers of circulating neutrophils and proinflammatory Ly6C(hi) monocytes in mice fed regular chow or a high-fat diet. Finally, the beneficial immune-associated effects were accompanied by amelioration of IR and improved insulin signaling in liver and adipose tissue. Collectively, our results describe key beneficial immunoregulatory properties for GIP in DIO and reveal that its augmentation ameliorates adipose tissue inflammation and improves IR. Copyright © 2014 by The American Association of Immunologists, Inc.

  17. Provision of no-cost, long-acting contraception and teenage pregnancy.

    Science.gov (United States)

    Secura, Gina M; Madden, Tessa; McNicholas, Colleen; Mullersman, Jennifer; Buckel, Christina M; Zhao, Qiuhong; Peipert, Jeffrey F

    2014-10-02

    The rate of teenage pregnancy in the United States is higher than in other developed nations. Teenage births result in substantial costs, including public assistance, health care costs, and income losses due to lower educational attainment and reduced earning potential. The Contraceptive CHOICE Project was a large prospective cohort study designed to promote the use of long-acting, reversible contraceptive (LARC) methods to reduce unintended pregnancy in the St. Louis region. Participants were educated about reversible contraception, with an emphasis on the benefits of LARC methods, were provided with their choice of reversible contraception at no cost, and were followed for 2 to 3 years. We analyzed pregnancy, birth, and induced-abortion rates among teenage girls and women 15 to 19 years of age in this cohort and compared them with those observed nationally among U.S. teens in the same age group. Of the 1404 teenage girls and women enrolled in CHOICE, 72% chose an intrauterine device or implant (LARC methods); the remaining 28% chose another method. During the 2008-2013 period, the mean annual rates of pregnancy, birth, and abortion among CHOICE participants were 34.0, 19.4, and 9.7 per 1000 teens, respectively. In comparison, rates of pregnancy, birth, and abortion among sexually experienced U.S. teens in 2008 were 158.5, 94.0, and 41.5 per 1000, respectively. Teenage girls and women who were provided contraception at no cost and educated about reversible contraception and the benefits of LARC methods had rates of pregnancy, birth, and abortion that were much lower than the national rates for sexually experienced teens. (Funded by the Susan Thompson Buffett Foundation and others.).

  18. Loss of Asthma Control in Pediatric Patients after Discontinuation of Long-Acting Beta-Agonists

    Directory of Open Access Journals (Sweden)

    Adrian R. O'Hagan

    2012-01-01

    Full Text Available Recent asthma recommendations advocate the use of long-acting beta-agonists (LABAs in uncontrolled asthma, but also stress the importance of stepping down this therapy once asthma control has been achieved. The objective of this study was to evaluate downtitration of LABA therapy in pediatric patients who are well-controlled on combination-inhaled corticosteroid (ICS/LABA therapy. Clinical and physiologic outcomes were studied in children with moderate-to-severe persistent asthma after switching from combination (ICS/LABA to monotherapy with ICS. Of the 54 patients, 34 (63% were determined to have stable asthma after the switch, with a mean followup of 10.7 weeks. Twenty (37% had loss of asthma control leading to addition of leukotriene receptor antagonists, increased ICS, or restarting LABA. There were 2 exacerbations requiring treatment with systemic steroids. In patients with loss of control, there was a statistically significant decline in FEV1 (−8% versus −1.9%, =0.03 and asthma control test (−3.2 versus −0.5, =0.03. This did not approach significance for FEF25-75%, exhaled nitric oxide, lung volumes or airway reactivity. No demographic, asthma control measures, or lung function variables predicted loss of control. Pediatric patients with moderate-to-severe persistent asthma who discontinue LABA therapy have a 37% chance of losing asthma control resulting in augmented maintenance therapies. Recent recommendations of discontinuing LABA therapy as soon as control is achieved should be evaluated in a prospective long-term study.

  19. Relevance of dosage in adherence to treatment with long-acting anticholinergics in patients with COPD

    Directory of Open Access Journals (Sweden)

    Izquierdo JL

    2016-02-01

    Full Text Available José Luis Izquierdo,1 José Manuel Paredero,2 Raul Piedra3 1Department of Pneumology, Hospital Universitario de Guadalajara, 2Department of Pharmacy, 3Department of Primary Care, Guadalajara Integrated Care Management, Guadalajara, Spain Introduction: The aim of this study was to assess the degree of adherence for two standard regimens for administrating anticholinergic drugs (12 and 24 hours in patients with chronic obstruction of the airflow and to establish whether the use of a once-daily dose improves the level of treatment adherence.Methods: We used long-acting anticholinergics (LAMAs as a study variable, and included the entire health area of Castile-La Mancha, numbering 2,100,998 inhabitants, as the study population. We analyzed a total of 16,446 patients who had been prescribed a LAMA between January 1, 2013 and December 31, 2013. The follow-up period, based on a centralized system of electronic prescription management, was extended until December 2014.Results: During 2013, the medication collected was 7.4%–10.7% higher than indicated by labeling. This was very similar for all LAMAs, irrespective of the patient’s sex, the molecule, the device, and the drug dosage. We did not observe seasonal variations in the consumption of LAMAs, nor did we detect differences between prescription drugs for once-daily (every 24 hours versus twice-daily (every 12 hours administration, between the different molecules, or between different types of inhalers for the same molecule. The results were similar in 2014.Conclusion: The principal conclusion of this study is that, in an area with a centralized management system of pharmacological prescriptions, adherence to treatment with LAMAs is very high, irrespective of the molecules or inhalation device. We did not find that patients who used twice-daily medication had a lower adherence. Keywords: COPD, treatment, adherence, LABAs, LAMAs, PDC, asthma

  20. Long-acting Reversible Contraception for Adolescents and Young Adults: Patient and Provider Perspectives

    Science.gov (United States)

    Kavanaugh, Megan L.; Frohwirth, Lori; Jerman, Jenna; Popkin, Ronna; Ethier, Kathleen

    2013-01-01

    Study objective To describe and explore provider- and patient-level perspectives regarding long-acting reversible contraception (LARC) for teens and young adults (ages 16-24). Methods Data collection occurred between June – December 2011. We first conducted telephone interviews with administrative directors at 20 publicly funded facilities that provide family planning services. At six of these sites, we conducted a total of six focus group discussions (FGDs) with facility staff and forty-eight in-depth interviews (IDIs) with facility clients ages 16-24. Results Staff in the FGDs did not generally equate being a teen with ineligibility for IUDs. In contrast to staff, one quarter of the young women did perceive young age as rendering them ineligible. Clients and staff agreed that the “forgettable” nature of the methods and their duration were some of LARC’s most significant advantages. They also agreed that fear of pain associated with both insertion and removal and negative side effects were disadvantages. Some aspects of IUDs and implants were perceived as advantages by some clients but disadvantages by others. Common challenges to providing LARC-specific services to younger patients included extra time required to counsel young patients about LARC methods, outdated clinic policies requiring multiple visits to obtain IUDs, and a perceived higher removal rate among young women. The most commonly cited strategy for addressing many of these challenges was securing supplementary funding to support the provision of these services to young patients. Conclusion Incorporating young women’s perspectives on LARC methods into publicly funded family planning facilities’ efforts to provide these methods to a younger population may increase their use among young women. PMID:23287602

  1. Post-abortion initiation of long-acting reversible contraception in New Zealand.

    Science.gov (United States)

    Rose, Sally B; Garrett, Susan M

    2015-07-01

    Post-abortion initiation of long-acting reversible contraception (LARC) reduces subsequent abortion rates within 24 months, but the prevalence of post-abortion LARC use in New Zealand is unknown. To describe post-abortion initiation of intrauterine and implantable LARC methods in New Zealand between 2007 and 2012, and to determine what impact the introduction of government-funded (free) levonorgestrel (LNG) implants in August 2010 had on overall LARC use. Retrospective observational study involving New Zealand abortion clinic data. Nationally collated data on post-abortion LARC insertions were obtained for the period 2007-2012, and individual-level discharge data for patients attending a large urban hospital abortion clinic were analysed using descriptive statistics to describe annual uptake rates, and the demographic profile of LARC users during this period. Logistic regression analyses examined whether LARC use differed by parity and/or age over time. Post-abortion LARC use increased from 20.2% in 2007 to 45.6% in 2012. Intrauterine device use increased from 20.2% to 31.8% during this period, with implants contributing a further 14% to the overall use of LARC methods by 2012. Clinic data showed that LARC use increased among most demographic subgroups between 2009 and 2012, with the greatest increase among nulliparous under-20-year-olds (from 17.2% to 42.0%). Post-abortion LARC use has been steadily increasing in New Zealand since 2007. Overall LARC use significantly increased following the introduction of government-funded implants, particularly among young and nulliparous women. Improving access to alternative methods of LARC may further increase uptake and reduce unwanted pregnancy rates. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. Who is using long-acting reversible contraceptive methods? Findings from nine low-fertility countries.

    Science.gov (United States)

    Eeckhaut, Mieke C W; Sweeney, Megan M; Gipson, Jessica D

    2014-09-01

    Long-acting reversible contraceptive (LARC) methods-IUDs and implants-are more effective than other reversible methods, yet are little used in the United States. Examining which U.S. women use LARC methods and how they differ from users in other low-fertility countries may help point the way toward increasing use. Data from married or cohabiting women participating in the National Survey of Family Growth (2008-2010) and in eight countries' Generations and Gender Programme surveys (2004-2010) were used in bivariate and multinomial logistic regression analyses examining LARC use within each setting. The proportion of contraceptive use accounted for by LARC methods was generally greater in Europe (10-32%) than in the United States (10%) and Australia (7%). Compared with LARC use among comparable groups in other countries, use was particularly low among U.S. women who were married, were aged 40-44 or had had three or more children, yet was comparatively high among 18-24-year-olds. Among U.S. women, those aged 35-39 or 40-44 were more likely than 18-29-year-olds to rely on sterilization rather than on LARC methods (odds ratios, 3.0 and 10.7, respectively), those who had had three or more children were more likely to do so than were those who had had none or one (4.9), and women who had completed college were less likely than those who had not finished high school to do so (0.4). Certain subgroups of U.S. women may benefit from the reversibility and effectiveness of LARC methods. Copyright © 2014 by the Guttmacher Institute.

  3. Postabortion contraception: qualitative interviews on counseling and provision of long-acting reversible contraceptive methods.

    Science.gov (United States)

    Morse, Jessica; Freedman, Lori; Speidel, J Joseph; Thompson, Kirsten M J; Stratton, Laura; Harper, Cynthia C

    2012-06-01

    Long-acting reversible contraceptive (LARC) methods (IUDs and implants) are the most effective and cost-effective methods for women. Although they are safe to place immediately following an abortion, most clinics do not offer this service, in part because of the increased cost. In 2009, telephone interviews were conducted with 20 clinicians and 24 health educators at 25 abortion care practices across the country. A structured topic guide was used to explore general practice characteristics; training, knowledge and attitudes about LARC; and postabortion LARC counseling and provision. Transcripts of the digitally recorded interviews were coded and analyzed using inductive and deductive processes. Respondents were generally positive about the safety and effectiveness of LARC methods; those working in clinics that offered LARC methods immediately postabortion tended to have greater knowledge about LARC than others, and to perceive fewer risks and employ more evidence-based practices. LARC methods often were not included in contraceptive counseling for women at high risk of repeat unintended pregnancy, including young and nulliparous women. Barriers to provision were usually expressed in terms of financial cost--to patients and clinics--and concerns about impact on the smooth flow of clinic procedures. Education and encouragement from professional colleagues regarding LARC, as well as training and adequate reimbursement for devices, were considered critical to changing clinical practice to include immediate postabortion LARC provision. Despite evidence about the safety and cost-effectiveness of postabortion LARC provision, many clinics are not offering it because of financial and logistical concerns, resulting in missed opportunities for preventing repeat unintended pregnancies. Copyright © 2012 by the Guttmacher Institute.

  4. Long-Acting Reversible Contraceptive Placement Among Active-Duty U.S. Army Servicewomen.

    Science.gov (United States)

    Erickson, Anne K; Nelson, D Alan; Shaw, Jonathan G; Loftus, Pooja D; Kurina, Lianne M; Shaw, Kate A

    2017-05-01

    To quantify uptake of long-acting reversible contraceptives (LARC)-intrauterine devices (IUDs) and hormonal implants-among U.S. Army active-duty female soldiers and identify characteristics associated with uptake. This retrospective cohort study used the Stanford Military Data Repository, which includes all digitally recorded health encounters for active-duty U.S. Army soldiers from 2011 to 2014. We analyzed data from women aged 18-44 years to assess rates of LARC initiation using medical billing codes. We then evaluated predictors of LARC initiation using multivariable regression. Among 114,661 servicewomen, 14.5% received a LARC method; among those, 60% received an IUD. Intrauterine device insertions decreased over the study period (38.7-35.9 insertions per 1,000 women per year, β=0.14, 95% confidence interval [CI] -0.23 to -0.05, Pimplant insertions (20.3-35.4/1,000 women per year, β=0.41, CI 0.33-0.48, Pimplant users were in the youngest age category (18-22 years) compared with 9.6% and 2.0% in the oldest (36-44 years). The likelihood of uptake among the youngest women (compared with oldest) was most marked for implants (adjusted relative risk 7.12, CI 5.92-8.55; Pimplant use. Unmarried and childless soldiers were less likely to initiate LARC. These findings are consistent with potential underutilization and a need for education about LARC safety and reversibility in a population facing unique consequences for unintended pregnancies.

  5. Therapeutic Effect of Exendin-4, a Long-Acting Analogue of Glucagon-Like Peptide-1 Receptor Agonist, on Nerve Regeneration after the Crush Nerve Injury

    Directory of Open Access Journals (Sweden)

    Koji Yamamoto

    2013-01-01

    Full Text Available Glucagon-like peptide-1 (GLP-1 is glucose-dependent insulinotropic hormone secreted from enteroendocrine L cells. Its long-acting analogue, exendin-4, is equipotent to GLP-1 and is used to treat type 2 diabetes mellitus. In addition, exendin-4 has effects on the central and peripheral nervous system. In this study, we administered repeated intraperitoneal (i.p. injections of exendin-4 to examine whether exendin-4 is able to facilitate the recovery after the crush nerve injury. Exendin-4 injection was started immediately after crush injury and was repeated every day for subsequent 14 days. Rats subjected to sciatic nerve crush exhibited marked functional loss, electrophysiological dysfunction, and atrophy of the tibialis anterior muscle (TA. All these changes, except for the atrophy of TA, were improved significantly by the administration of exendin-4. Functional, electrophysiological, and morphological parameters indicated significant enhancement of nerve regeneration 4 weeks after nerve crush. These results suggest that exendin-4 is feasible for clinical application to treat peripheral nerve injury.

  6. Use of Long-Acting Somatostatin Analogue (Lanreotide) in an Adolescent with Diazoxide-Responsive Congenital Hyperinsulinism and Its Psychological Impact.

    Science.gov (United States)

    Shah, Pratik; Rahman, Sofia A; McElroy, Sharon; Gilbert, Clare; Morgan, Kate; Hinchey, Louise; Senniappan, Senthil; Levy, Hannah; Amin, Rakesh; Hussain, Khalid

    2015-01-01

    Congenital hyperinsulinism (CHI) is a common cause of hypoglycaemia due to unregulated insulin secretion from pancreatic β cells. Medical management includes use of oral diazoxide (a KATP channel agonist) and daily injectable octreotide (somatostatin analogue) therapy. However, diazoxide is associated with severe sideeffects such as coarse facies, hypertrichosis and psychosocial/compliance issues in adolescents. Lanreotide (a long-acting somatostatin analogue) is used in adults with neuroendocrine tumours; however, its role in patients with CHI has not been well described. A 15-year-old girl with diazoxide-responsive CHI had severe hypertrichosis secondary to diazoxide and subsequent compliance/psychosocial issues. She was commenced on 30 mg of lanreotide every 4 weeks as a deep subcutaneous injection, in an attempt to address these issues. She was able to come off diazoxide treatment 2 months after starting lanreotide. Presently, after 2.5 years of lanreotide treatment, her blood glucose control is stable with complete resolution of hypertrichosis. Clinically significant improvements in the self-reported Paediatric Quality of Life (PedsQL) questionnaire and Strengths and Difficulties Questionnaire (SDQ) were reported after 1 year on lanreotide. No side effects were found, and her liver/thyroid function and abdominal ultrasound have been normal. We report the first case on the use of lanreotide in an adolescent girl with diazoxide-responsive CHI with significant improvement of quality of life. © 2015 S. Karger AG, Basel.

  7. Olanzapine Versus Placebo in the Treatment of Adolescents With Bipolar Mania

    National Research Council Canada - National Science Library

    Robertson-Plouch, Carol; DelBello, Melissa; Lin, Daniel; Kryzhanovskaya, Ludmila; Xu, Wen; Biederman, Joseph; Tohen, Mauricio; Wagner, Karen; Carlson, Gabrielle; Dittmann, Ralf W; Wozniak, Janet; Kowatch, Robert; Findling, Robert

    2007-01-01

    Objective: The purpose of this study was to evaluate the efficacy and safety of olanzapine for the treatment of acute manic or mixed episodes associated with bipolar disorder in adolescents. Method...

  8. Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting

    Science.gov (United States)

    Navari, Rudolph M.; Qin, Rui; Ruddy, Kathryn J.; Liu, Heshan; Powell, Steven F.; Bajaj, Madhuri; Dietrich, Leah; Biggs, David; Lafky, Jacqueline M.; Loprinzi, Charles L.

    2016-01-01

    BACKGROUND We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy. METHODS In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3–receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide–doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point. RESULTS In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P = 0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P = 0.002), and the overall 120-hour period (37% vs. 22%, P = 0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P = 0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2. CONCLUSIONS Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.) PMID:27410922

  9. Olanzapine-induced Priapism in a Child with Asperger’s Syndrome

    Science.gov (United States)

    Bozkurt, Hasan; Şahin, Serkan

    2017-01-01

    Background: Priapism is a potentially painful and prolonged erection that occurs in the absence of any stimulation. Olanzapine has been reported to induce priapism in several adult cases with schizophrenia and/or mood disorders but very rarely reported in children. Case Report: 9-year-old male with Asperger’s Syndrome (AS) referred to our clinic with the complaints of inattention, hyperactivity and impulsivity. He was diagnosed with attention deficit hyperactivity disorder (ADHD) and given methylphenidate treatment which ameliorated his ADHD symptoms. He started to have severe loss of appetite after methylphenidate treatment so olanzapine 2.5 mg/day was added to cope with severe inappetence. However he experienced priapism after olanzapine and priapism resolved after ceasing the drug. His mother restarted olanzapine because he benefited from olanzapine. But the same episodes occurred soon after olanzapine again and his mother had to stop the medication. Conclusion: Because atypical antipsychotics are now widely used in children, unusual side effects such as priapism should be taken into consideration for the differential diagnosis. PMID:28251031

  10. The promotion of olanzapine in primary care: an examination of internal industry documents.

    Science.gov (United States)

    Spielmans, Glen I

    2009-07-01

    Media reports have discussed how olanzapine was marketed off-label for dementia and subsyndromal bipolar disorder. Much of this marketing occurred in primary care settings. However, these reports have provided few details. In legal proceedings, Lilly disclosed internal documents that detail the strategies utilized to market olanzapine. The current paper addresses the marketing of olanzapine in detail based upon a review of these documents. All 358 documents released by Lilly are publicly available online. Documents were utilized for this review if they were relevant to the marketing of olanzapine in primary care settings in the United States. It was found that olanzapine was marketed off-label in primary care settings for relatively mild symptoms that were framed as bipolar disorder and schizophrenia. A key strategy in this campaign was the use of hypothetical patient profiles in detailing visits, most of which clearly failed to meet diagnostic criteria for any recognized mental disorder. Evidence emerged that olanzapine was also marketed off-label as a treatment for dementia.

  11. An unusual case of hypothermia associated with therapeutic doses of olanzapine: a case report

    Directory of Open Access Journals (Sweden)

    Ratnayake Shiroma L

    2011-05-01

    Full Text Available Abstract Introduction We report a case of a 42-year-old man who had symptomatic hypothermia as a result of taking olanzapine for paranoid schizophrenia. According to published data, only a few cases of hypothermia associated with olanzapine have been reported since its introduction into clinical use. Case presentation A 42-year-old Sri Lankan man with schizophrenia who was being treated with a therapeutic dose of olanzapine presented with reduced level of consciousness. He had a core temperature of 32°C and was bradycardic. At the time of admission, the electrocardiogram showed sinus bradycardia with J waves. He did not have any risk factors for developing hypothermia except the use of olanzapine. There was improvement in his clinical condition with reversal of electrocardiogram changes following gradual rewarming and the omission of olanzapine. Conclusion Hypothermia induced by antipsychotic medications is not uncommon, but olanzapine-induced hypothermia is rare and occurrence has been reported during initiation or increasing the dose. But here the patient developed hypothermia without dose adjustment.

  12. Betahistine decreases olanzapine-induced weight gain and somnolence in humans.

    Science.gov (United States)

    Barak, Nir; Beck, Yaffa; Albeck, Joseph H

    2016-03-01

    Olanzapine's efficacy in schizophrenia is attributed to antagonism of dopamine and serotonin receptors. Olanzapine is also a potent histamine-H1 antagonist that results in weight gain and somnolence. Betahistine is a centrally acting histamine-H1 agonist, and therefore may reduce olanzapine's effect on histamine receptors in the brain. Olanzapine's high affinity for the histamine-H1 receptor warrants the use of high doses of betahistine. Forty-eight healthy women were recruited and randomized to receive either betahistine 144 mg/day or matching placebo for 4 weeks. Due to the high dose of betahistine, olanzapine was started only on the second week and titrated up to 10 mg/day, and co-administration continued for an additional 2 weeks. Only nominal differences in adverse events were noted between the treatment groups. Betahistine caused a 37% reduction in mean weight gain (1.24 kg in the betahistine arm vs. 1.93 kg in the placebo arm; p=.049) and 60% reduction in the mean increase in daytime Epworth sleepiness scores (1.82 units in the betahistine group vs. 3.57 units in the placebo group; p=.042). The present study suggests that betahistine-olanzapine co-administration, in healthy female subjects, yields an acceptable safety profile with mitigation of weight gain and somnolence. This should be further tested in a patient cohort.

  13. A Comparative Study between Olanzapine and Risperidone in the Management of Schizophrenia

    Directory of Open Access Journals (Sweden)

    Saeed Shoja Shafti

    2014-01-01

    Full Text Available Introduction. Since a variety of comparisons between risperidone and olanzapine have resulted in diverse outcomes, so safety and efficacy of them were compared again in a new trial. Method. Sixty female schizophrenic patients entered into one of the assigned groups for random allocation to olanzapine or risperidone (n=30 in each group in a double-blind, 12-week clinical trial. Scale for Assessment of Positive Symptoms (SAPS and Scale for Assessment of Negative Symptoms (SANS were used as the primary outcome measures. Clinical Global Impressions-Severity Scale (CGI-S, Schedule for Assessment of Insight (SAI, and finally Simpson Angus Scale (SAS as well were employed as secondary scales. Results. While both of olanzapine and risperidone were significantly effective for improvement of positive symptoms (P<0.0001, as regards negative symptoms, it was so only by means of olanzapine (P<0.0003. CGI-S and SAI, as well, were significantly improved in both of the groups. SAS increment was significant only in the risperidone group (P<0.02. Conclusion. While both of olanzapine and risperidone were equally effective for improvement of positive symptoms and insight, olanzapine showed superior efficacy with respect to negative symptoms, along with lesser extrapyramidal side effects, in comparison with risperidone.

  14. Thrombocytopenia associated with olanzapine: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Swapnajeet Sahoo

    2016-01-01

    Full Text Available There is limited literature on olanzapine-associated thrombocytopenia. In this report, we present a case of a 32-year-old female, suffering from persistent delusional disorder who had thrombocytopenia (46,000/mm3 with the use of olanzapine 25 mg/day, 6 weeks after starting medication. Blood film did not reveal any evidence of any dysplastic cells, disturbance in the count of other cell lines, and autoimmune workup including antinuclear antibodies and anti-neutrophil cytoplasmic antibodies were found to be negative. Given no other etiology, olanzapine was gradually tapered, and platelet counts were monitored. Reduction in the dose of olanzapine led to an improvement in platelet counts which reached the normal range after complete stoppage of olanzapine. In view of continued psychotic symptoms, she was started on clozapine and which was gradually increased to 200 mg/day with biweekly monitoring of total platelet counts before each increment in the dose of clozapine. Thrombocytopenia did not recur with use of clozapine. With clozapine, her psychosis improved by nearly 60%. A review of literature revealed only eight case reports supporting the association of olanzapine and thrombocytopenia.

  15. Bioequivalence Study of Two Long-Acting Formulations of Oxytetracycline Following Intramuscular Administration in Bovines

    Science.gov (United States)

    Mestorino, Nora; Marchetti, María Laura; Lucas, Mariana Florencia; Modamio, Pilar; Zeinsteger, Pedro; Fernández Lastra, Cecilia; Segarra, Ignacio; Mariño, Eduardo Luis

    2016-01-01

    The aim of this study was to evaluate the bioequivalence of two commercial long-acting formulations based on oxytetracycline (OTC) hydrochloride between the reference formulation (Terramycin LA, Pfizer) and a test formulation (Cyamicin LA, Fort Dodge Saude Animal). Both formulations were administered in a single intramuscular route at a dose of 20 mg OTC/kg of body weight in clinically healthy bovines. The study was carried out according to a one-period parallel design. Plasma samples were analyzed by high-pressure liquid chromatography. The limit of quantitation was 0.050 μg/mL with an accuracy of 101.67% with a coefficient of variation of 13.15%. Analysis of variance and 90% confidence interval tests were used to compare the bioavailability parameters (maximum plasma concentration, Cmax, and the area under the concentration-versus-time curve extrapolated to infinity, AUC0–∞) of both products. In the case of the time to maximum concentration (Tmax), non-parametric tests based on Wilcoxon’s signed rank test were preferred. The comparison of the mean AUC0–∞ values did not reveal any significant differences (311.40 ± 93.05 μg h/mL and 287.71 ± 45.31 μg h/mL, respectively). The results were similar for the Tmax (3.58 ± 0.90 h versus 3.42 ± 0.51 h). However, when comparing the mean Cmax some significant differences were found (8.73 ± 3.66 μg/mL and 10.43 ± 3.84 μg/mL, respectively). The 90% confidence intervals for the ratio of AUC0–∞ and Tmax values for the reference and test product are within the interval 80–125%, but the 90% confidence intervals for the ratio of Cmax falls outside the proposed interval. It was concluded that Cmax of test product are not within the 20% of those of the reference, thus suggesting that test OTC is not bioequivalent to the reference formulation. PMID:27446938

  16. Vouchers in Fragile States: Reducing Barriers to Long-Acting Reversible Contraception in Yemen and Pakistan.

    Science.gov (United States)

    Boddam-Whetham, Luke; Gul, Xaher; Al-Kobati, Eman; Gorter, Anna C

    2016-08-11

    In conflict-affected states, vouchers have reduced barriers to reproductive health services and have enabled health programs to use targeted subsidies to increase uptake of specific health services. Vouchers can also be used to channel funds to public- and private-service providers and improve service quality. The Yamaan Foundation for Health and Social Development in Yemen and the Marie Stopes Society (MSS) in Pakistan-both working with Options Consultancy Services-have developed voucher programs that subsidize voluntary access to long-acting reversible contraceptives (LARCs) and permanent methods (PMs) of family planning in their respective fragile countries. The programs focus on LARCs and PMs because these methods are particularly difficult for poor women to access due to their cost and to provider biases against offering them. Using estimates of expected voluntary uptake of LARCs and PMs for 2014 based on contraceptive prevalence rates, and comparing these with uptake of LARCs and PMs through the voucher programs, we show the substantial increase in service utilization that vouchers can enable by contributing to an expanded method choice. In the governorate of Lahj, Yemen, vouchers for family planning led to an estimated 38% increase in 2014 over the expected use of LARCs and PMs (720 vs. 521 expected). We applied the same approach in 13 districts of Punjab, Khyber Pakhtunkhwa (KPK), and Sindh provinces in Pakistan. Our calculations suggest that vouchers enabled 10 times more women than expected to choose LARCs and PMs in 2014 in those areas of Pakistan (73,639 vs. 6,455 expected). Voucher programs can promote and maintain access to family planning services where existing health systems are hampered. Vouchers are a flexible financing approach that enable expansion of contraceptive choice and the inclusion of the private sector in service delivery to the poor. They can keep financial resources flowing where the public sector is prevented from offering services

  17. Bioequivalence Study of Two Long-Acting Formulations of Oxytetracycline Following Intramuscular Administration in Bovines.

    Science.gov (United States)

    Mestorino, Nora; Marchetti, María Laura; Lucas, Mariana Florencia; Modamio, Pilar; Zeinsteger, Pedro; Fernández Lastra, Cecilia; Segarra, Ignacio; Mariño, Eduardo Luis

    2016-01-01

    The aim of this study was to evaluate the bioequivalence of two commercial long-acting formulations based on oxytetracycline (OTC) hydrochloride between the reference formulation (Terramycin LA, Pfizer) and a test formulation (Cyamicin LA, Fort Dodge Saude Animal). Both formulations were administered in a single intramuscular route at a dose of 20 mg OTC/kg of body weight in clinically healthy bovines. The study was carried out according to a one-period parallel design. Plasma samples were analyzed by high-pressure liquid chromatography. The limit of quantitation was 0.050 μg/mL with an accuracy of 101.67% with a coefficient of variation of 13.15%. Analysis of variance and 90% confidence interval tests were used to compare the bioavailability parameters (maximum plasma concentration, C max, and the area under the concentration-versus-time curve extrapolated to infinity, AUC0-∞) of both products. In the case of the time to maximum concentration (T max), non-parametric tests based on Wilcoxon's signed rank test were preferred. The comparison of the mean AUC0-∞ values did not reveal any significant differences (311.40 ± 93.05 μg h/mL and 287.71 ± 45.31 μg h/mL, respectively). The results were similar for the T max (3.58 ± 0.90 h versus 3.42 ± 0.51 h). However, when comparing the mean C max some significant differences were found (8.73 ± 3.66 μg/mL and 10.43 ± 3.84 μg/mL, respectively). The 90% confidence intervals for the ratio of AUC0-∞ and T max values for the reference and test product are within the interval 80-125%, but the 90% confidence intervals for the ratio of C max falls outside the proposed interval. It was concluded that C max of test product are not within the 20% of those of the reference, thus suggesting that test OTC is not bioequivalent to the reference formulation.

  18. Long-acting reversible contraception use among residents in obstetrics/gynecology training programs

    Directory of Open Access Journals (Sweden)

    Zigler RE

    2017-01-01

    Full Text Available Rachel E Zigler,1 Jeffrey F Peipert,1,2 Qiuhong Zhao,1 Ragini Maddipati,1 Colleen McNicholas1 1Department of Obstetrics and Gynecology, Division of Clinical Research and Family Planning, Washington University School of Medicine in St. Louis, St. Louis, MO, 2Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, USA Background: The objective of the study was to estimate the personal usage of long-acting reversible contraception (LARC among obstetrics and gynecology (Ob/Gyn residents in the United States and compare usage between programs with and without a Ryan Residency Training Program (Ryan Program, an educational program implemented to enhance resident training in family planning. Materials and methods: We performed a web-based, cross-sectional survey to explore contraceptive use among Ob/Gyn residents between November and December 2014. Thirty-two Ob/Gyn programs were invited to participate, and 24 programs (75% agreed to participate. We divided respondents into two groups based on whether or not their program had a Ryan Program. We excluded male residents without a current female partner as well as residents who were currently pregnant or trying to conceive. We evaluated predictors of LARC use using bivariate analysis and multivariable Poisson regression. Results: Of the 638 residents surveyed, 384 (60.2% responded to our survey and 351 were eligible for analysis. Of those analyzed, 49.3% (95% confidence interval [CI]: 44.1%, 54.5% reported current LARC use: 70.0% of residents in Ryan Programs compared to 26.8% in non-Ryan Programs (RRadj 2.14, 95% CI 1.63–2.80. Residents reporting a religious affiliation were less likely to use LARC than those who described themselves as non-religious (RRadj 0.76, 95% CI 0.64–0.92. Of residents reporting LARC use, 91% were using the levonorgestrel intrauterine device. Conclusion: LARC use in this population of women’s health specialists is substantially

  19. Double benefit of long-acting somatostatin analogs in a patient with coexistence of acromegaly and ulcerative colitis.

    Science.gov (United States)

    Yarman, S; Yalın, G Y; Dogansen, S C; Canbaz, B; Tanrıkulu, S; Akyuz, F

    2016-10-01

    Somatostatin analogs control GH/IGF-1 excess in acromegaly. Somatostatin receptors also mediate the complex effects of somatostatin on the gastrointestinal tract and may be defensive in inflammatory bowel diseases, such as ulcerative colitis. We present a patient who showed good response to long-acting octreotide (OCT-LAR) treatment in terms of both acromegaly and ulcerative colitis (UC). A 58-year-old female patient with diagnosis of acromegaly and ulcerative colitis was started on long-acting somatostatin treatment as a first-line treatment for acromegaly as she refused to undergo transsphenoidal surgery. During the follow-up period, a significant amelioration was also observed in the course of ulcerative colitis, and clinical remission of both diseases was achieved uneventfully. Somatostatin appears to be a promising candidate in the treatment of inflammatory bowel diseases. © 2016 John Wiley & Sons Ltd.

  20. Multispecies resistance of cattle gastrointestinal nematodes to long-acting avermectin formulations in Mato Grosso do Sul.

    Science.gov (United States)

    Borges, Fernando de Almeida; Borges, Dyego Gonçalves Lino; Heckler, Rafael Pereira; Neves, Juliana Paniago Lordello; Lopes, Fernando Gonçalves; Onizuka, Marcel Kenzo Vilalba

    2015-09-15

    The use of long-acting avermectins (AVMs) in cattle to treat infections with gastrointestinal nematodes was common in Brazil until its prohibition by state authorities. The prohibition; however, was rescinded in 2015, but a scientific discussion of the pros and cons of the use of these formulations is necessary. We evaluated the levels of resistance to 1.0 and 3.5% doramectin and to 3.15% ivermectin in cattle. The worms in animals treated with 3.5% doramectin were characterized by the suppression of oviposition and by a higher proportion of adult females carrying no eggs. Haemonchus placei, Cooperia punctata, C. pectinata, C. spatulata, and Oesophagostomum radiatum were resistant to the above compositions. The administration of long-acting AVM formulations did not result in a higher efficacy against these helminth populations.

  1. In Vitro and in Vivo Characterization of MOD-4023, a Long-Acting Carboxy-Terminal Peptide (CTP)-Modified Human Growth Hormone.

    Science.gov (United States)

    Hershkovitz, Oren; Bar-Ilan, Ahuva; Guy, Rachel; Felikman, Yana; Moschcovich, Laura; Hwa, Vivian; Rosenfeld, Ron G; Fima, Eyal; Hart, Gili

    2016-02-01

    MOD-4023 is a novel long-acting version of human growth hormone (hGH), containing the carboxy-terminal peptide (CTP) of human chorionic gonadotropin (hCG). MOD-4023 is being developed as a treatment for adults and children with growth hormone deficiency (GHD), which would require fewer injections than currently available GH formulations and thus reduce patient discomfort and increase compliance. This study characterizes MOD-4023's binding affinities for the growth hormone receptor, as well as the pharmacokinetic and pharmacodynamics, toxicology, and safety profiles of repeated dosing of MOD-4023 in Sprague-Dawley rats and Rhesus monkeys. Although MOD-4023 exhibited reduced in vitro potency and lower affinity to the GH receptor than recombinant hGH (rhGH), administration of MOD-4023 every 5 days in rats and monkeys resulted in exposure comparable to daily rhGH, and the serum half-life of MOD-4023 was significantly longer. Repeated administration of MOD-4023 led to elevated levels of insulin-like growth factor 1 (IGF-1), and twice-weekly injections of MOD-4023 resulted in larger increase in weight gain with fewer injections and a lower accumulative hGH dose. Thus, the increased half-life of MOD-4023 in comparison to hGH may increase the frequency of protein-receptor interactions and compensate for its decreased in vitro potency. MOD-4023 was found to be well-tolerated in rats and monkeys, with minimal adverse events, suggesting an acceptable safety profile. These results provide a basis for the continued clinical development of MOD-4023 as a novel treatment of GHD in children and adults.

  2. [Side effects of treatment with the long-acting gonadorelin agonist triptorelin in a case of paraphilia].

    Science.gov (United States)

    Hoogeveen, J H; van der Veer, E

    2007-01-01

    A 35-year-old man with a paraphilia was treated with long-acting gonadorelin. The desired result was reduced preoccupation with sexuality, but there were various side effects including a serious amount of bone loss. We believe that more attention should be given to the adverse effects of long-term treatment with triptorelin. In our view the drug regimen needs to be revised.

  3. Comparison of conventional and long-acting oxytetracyclines in prevention of induced Actinobacillus (Haemophilus) pleuropneumoniae infection of growing swine.

    OpenAIRE

    Kiorpes, A L; Bäckström, L R; Collins, M T; Kruse, G O

    1989-01-01

    These experiments tested the hypothesis that long-acting oxytetracycline (oxytetracycline-LA) was more effective than regular oxytetracycline in preventing porcine pleuropneumonia when administered either 24 or 48 h prior to experimental challenge with virulent strains of Actinobacillus pleuropneumoniae. Two experiments (1 and 2) were conducted using growing pigs (average weight 12-15 kg). Antibiotic treatments were administered once intramuscularly at 20 mg/kg body weight; controls received ...

  4. Knowledge and Perception on Long Acting and Permanent Contraceptive Methods in Adigrat Town, Tigray, Northern Ethiopia: A Qualitative Study

    Directory of Open Access Journals (Sweden)

    Alem Gebremariam

    2014-01-01

    Full Text Available Background. Long acting and permanent contraceptive methods have the potential to reduce unintended pregnancies but the contraceptive choice and utilization in Ethiopia are highly dominated by short term contraceptives. Objective. To assess the knowledge and perception on long acting and permanent contraceptives of married women and men in Northern Ethiopia. Method. A qualitative method was conducted in Adigrat on January, 2012. Four focus group discussions with married women and men and six in-depth interviews with family planning providers were conducted. Content analysis was used to synthesize the data. Result. Participants’ knowledge on long acting and permanent contraceptives is limited to recognizing the name of the methods. Most of the participants are not able to identify permanent methods as a method of contraception. They lack basic information on how these methods work and how they can use it. Women had fears and rumors about each of these methods. They prefer methods which do not require any procedure. Family planning providers stated as they have weakness on counseling of all contraceptive choices. Conclusion. There are personal barriers and knowledge gaps on these contraceptive methods. Improving the counseling service program can help women to increase knowledge and avoid misconceptions of each contraceptive choice.

  5. The effects of long-acting bronchodilators on total mortality in patients with stable chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Kliber Agnes

    2010-05-01

    Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD is the 4th leading cause of mortality worldwide. Long-acting bronchodilators are considered first line therapies for patients with COPD but their effects on mortality are not well known. We performed a comprehensive systematic review and meta-analysis to evaluate the effects of long-acting bronchodilators on total mortality in stable COPD. Methods Using MEDLINE, EMBASE and Cochrane Systematic Review databases, we identified high quality randomized controlled trials of tiotropium, formoterol, salmeterol, formoterol/budesonide or salmeterol/fluticasone in COPD that had a follow-up of 6 months or longer and reported on total mortality. Two reviewers independently abstracted data from the original trials and disagreements were resolved by iteration and consensus. Results Twenty-seven trials that included 30,495 patients were included in the review. Relative risk (RR for total mortality was calculated for each of the study and pooled together using a random-effects model. The combination of inhaled corticosteroid (ICS and long-acting beta-2 agonist (LABA therapy was associated with reduced total mortality compared with placebo (RR, 0.80; p = 0.005. Neither tiotropium (RR, 1.08; p = 0.61 nor LABA by itself (RR, 0.90; p = 0.21 was associated with mortality. Conclusions A combination of ICS and LABA reduced mortality by approximately 20%. Neither tiotropium nor LABA by itself modifies all-cause mortality in COPD.

  6. Pregnancy and the long-acting insulin analogue: a case study.

    Science.gov (United States)

    Caronna, Silvana; Cioni, Federico; Dall'Aglio, Elisabetta; Arsenio, Leone

    2006-04-01

    R.S. is a 22 years old Caucasian woman suffering from obesity, hypertension and Type I Diabetes Mellitus since the age of 6 years. Type I DM treatment includes 3 insulin injections at meal time and one glargine injection at bedtime. The insulin therapy regimen was prolonged during pregnancy and continued after childbirth. Optimal glycemic compensations were monitored throughout the pregnancy using HbA1c variations and other standard controls included in the OBG routine protocols, all within normal values. The pregnancy ended at the 38th week of gestation with a caesarean birth, during which a 3,54 Kg healthy boy with an APGAR of 9 was born. Both the mother and the newborn resulted in perfect health conditions confirming that the possibility of using glargine insulin profiles during pregnancy in selected cases with close monitoring may exist.

  7. 200 THE USE OF LONG-ACTING FSH-MAP5 IN SHEEP SUPEROVULATION PROGRAMS.

    Science.gov (United States)

    Fry, R

    2016-01-01

    The administration of sustained-release FSH-MAP5 in a 2-injection protocol has been shown to be as effective as a multiple-FSH injection protocol in inducing superovulation in cattle (Bo and Mapletoft 2014 Theriogenology 81, 38) and in sheep (Fry et al. 2016 Reprod. Fertil. Dev. 28, 250); however, the effect on embryo quality in the latter experiment was unclear. The following experiment further investigated the effect of FSH-MAP5 on ovulation rate and embryo quality in a sheep multiple-ovulation embryo transfer (MOET) program conducted in the breeding season. Two hundred sixteen Dohne merino ewes received a 12-day CIDR-S device containing 0.33g of progesterone (Zoetis, Florham Park, NJ, USA) plus 200mg of FSH IM (Folltropin-V; Vetoquinol, Belleville, Canada) and 400IU of eCG IM (Pregnecol: Vetoquinol) in 4 treatment groups. Group 1 (n=51) received 7 injections (a.m., p.m.) of FSH in saline (2.5, 2.0, 1.5, 1.5, 1.0, 1.0, and 0.5mL) starting 2.5 days before CIDR withdrawal and 400IU of eCG in saline at the time of the first FSH injection. Group 2 (n=53) received 6 injections (a.m., p.m.) of FSH in saline (3.0, 2.0, 1.5, 1.5, 1.0, and 1.0mL) starting 2.5 days before CIDR withdrawal and 400IU of eCG in saline at CIDR withdrawal. Group 3 (n=56) received 3.3mL of FSH in hyaluronan (50mg of MAP5, Vetoquinol) and 400IU of eCG in saline 2.5 days before CIDR withdrawal and 1.7mL of FSH-MAP5 at 0.5 days before CIDR withdrawal. Group 4 (n=56) received 3.3mL of FSH-MAP5 at 2.5 days before CIDR withdrawal, 1.7mL of FSH-MAP5 at 0.5 days before CIDR withdrawal, and 400IU of eCG in saline at CIDR withdrawal. Ewes were inseminated with semen collected and pooled from 5 rams at 36 to 40h after CIDR withdrawal. Donor ewes were slaughtered 6 days after AI, corpora lutea were counted on the ovary, and ova/embryos were collected. Data for corpora lutea, total ova/embryo, and transferable embryo was analysed by the Kruskal-Wallis test and differences between groups were determined by the

  8. Treatment of sexual dysfunction of hypogonadal patients with long-acting testosterone undecanoate (Nebido).

    Science.gov (United States)

    Yassin, Aksam A; Saad, Farid

    2006-12-01

    Recently, testosterone undecanoate (TU), a new parenteral testosterone (T) preparation has been introduced. Two of its distinctive features are (a) its prolonged action: after two initial loading injections 6 weeks apart, usually only one injection every 12 weeks is needed (b) over the full interval between two injections, plasma T levels are in the physiological range. New research presents convincing evidence that T has profound effects on tissues of the penis involved in the mechanism of erection and that testosterone deficiency impairs the anatomical and physiological substrate of erectile capacity, which is, at least, in part reversible upon androgen therapy. Our studies with TU demonstrated that venous leakage could be corrected with T treatment in a number of patients. We further could show that sexual functions, in a substantial number of elderly men, can be restored with treatment with T only. So, these results argue for determination of T levels in elderly men with sexual problems. If the levels are subnormal, T treatment is warranted.

  9. Alterations to melanocortinergic, GABAergic and cannabinoid neurotransmission associated with olanzapine-induced weight gain.

    Directory of Open Access Journals (Sweden)

    Katrina Weston-Green

    Full Text Available BACKGROUND/AIM: Second generation antipsychotics (SGAs are used to treat schizophrenia but can cause serious metabolic side-effects, such as obesity and diabetes. This study examined the effects of low to high doses of olanzapine on appetite/metabolic regulatory signals in the hypothalamus and brainstem to elucidate the mechanisms underlying olanzapine-induced obesity. METHODOLOGY/RESULTS: Levels of pro-opiomelanocortin (POMC, neuropeptide Y (NPY and glutamic acid decarboxylase (GAD(65, enzyme for GABA synthesis mRNA expression, and cannabinoid CB1 receptor (CB1R binding density (using [(3H]SR-141716A were examined in the arcuate nucleus (Arc and dorsal vagal complex (DVC of female Sprague Dawley rats following 0.25, 0.5, 1.0 or 2.0 mg/kg olanzapine or vehicle (3×/day, 14-days. Consistent with its weight gain liability, olanzapine significantly decreased anorexigenic POMC and increased orexigenic NPY mRNA expression in a dose-sensitive manner in the Arc. GAD(65 mRNA expression increased and CB1R binding density decreased in the Arc and DVC. Alterations to neurotransmission signals in the brain significantly correlated with body weight and adiposity. The minimum dosage threshold required to induce weight gain in the rat was 0.5 mg/kg olanzapine. CONCLUSIONS: Olanzapine-induced weight gain is associated with reduced appetite-inhibiting POMC and increased NPY. This study also supports a role for the CB1R and GABA in the mechanisms underlying weight gain side-effects, possibly by altering POMC transmission. Metabolic dysfunction can be modelled in the female rat using low, clinically-comparable olanzapine doses when administered in-line with the half-life of the drug.

  10. H3 histamine receptor antagonist pitolisant reverses some subchronic disturbances induced by olanzapine in mice.

    Science.gov (United States)

    Dudek, Magdalena; Kuder, Kamil; Kołaczkowski, Marcin; Olczyk, Adrian; Żmudzka, Elżbieta; Rak, Aleksandra; Bednarski, Marek; Pytka, Karolina; Sapa, Jacek; Kieć-Kononowicz, Katarzyna

    2016-10-01

    The use of atypical antipsychotic drugs like olanzapine is associated with side effects such as sedation and depression-like symptoms, especially during the initial period of the use. It is believed that the occurrence of these undesirable effectsis mainly the result of the histamine H1receptors blockade by olanzapine. In addition, use of olanzapine increases the level of triglycerides in the blood, which correlates with growing obesity. The aim of this study was to investigate the influence of pitolisant - H3 histamine antagonist - on subchronic olanzapine-induced depresion-like symptoms, sedation and hypertriglicerydemia. Forced swim test was conducted to determinate depressive-like effect of olanzapine and antidepressive-like activity during the co-administered pitolisant. The test was performed after the first and fifteenth day of the treatment of the mice. The spontaneous activity of the mice was measured on the fourteenth day of the treatment with a special, innovative RFID-system (Radio-frequency identification system) - TraffiCage (TSE-Systems, Germany). Triglyceride levels were determined on the sixteenth day of the experiment after 15 cycles of drug administration. Daily olanzapine treatment (4 mg/kg b.w., i.p., d.p.d) for 15 days significantly induces sedation (p < 0.05) and prolongs immobility time in forced swim tests (FST) in mice (p < 0.05); and also elevates the level of triglycerides (p < 0.05). Administration of pitolisant (10 mg/kg b.w., i.p.) subsequentto olanzapine normalizes these adverse effects. This study presents a promising alternative for counteracting some behavioral changes and metabolic disturbances which occur in the early period of treatment with antipsychotic drugs.

  11. Long-acting beta-agonists in the management of chronic obstructive pulmonary disease: current and future agents

    Directory of Open Access Journals (Sweden)

    Fabbri Leonardo M

    2010-10-01

    Full Text Available Abstract Chronic obstructive pulmonary disease (COPD is characterized by progressive airflow limitation and debilitating symptoms. For patients with moderate-to-severe COPD, long-acting bronchodilators are the mainstay of therapy; as symptoms progress, guidelines recommend combining bronchodilators from different classes to improve efficacy. Inhaled long-acting β2-agonists (LABAs have been licensed for the treatment of COPD since the late 1990s and include formoterol and salmeterol. They improve lung function, symptoms of breathlessness and exercise limitation, health-related quality of life, and may reduce the rate of exacerbations, although not all patients achieve clinically meaningful improvements in symptoms or health related quality of life. In addition, LABAs have an acceptable safety profile, and are not associated with an increased risk of respiratory mortality, although adverse effects such as palpitations and tremor may limit the dose that can be tolerated. Formoterol and salmeterol have 12-hour durations of action; however, sustained bronchodilation is desirable in COPD. A LABA with a 24-hour duration of action could provide improvements in efficacy, compared with twice-daily LABAs, and the once-daily dosing regimen could help improve compliance. It is also desirable that a new LABA should demonstrate fast onset of action, and a safety profile at least comparable to existing LABAs. A number of novel LABAs with once-daily profiles are in development which may be judged against these criteria. Indacaterol, a LABA with a 24-hour duration of bronchodilation and fast onset of action, is the most advanced of these. Preliminary results from large clinical trials suggest indacaterol improves lung function compared with placebo and other long-acting bronchodilators. Other LABAs with a 24-hour duration of bronchodilation include carmoterol, vilanterol trifenatate and oldaterol, with early results indicating potential for once-daily dosing in

  12. Novel GLP-1 Fusion Chimera as Potent Long Acting GLP-1 Receptor Agonist

    OpenAIRE

    Qinghua Wang; Kui Chen; Rui Liu; Fang Zhao; Sandeep Gupta; Nina Zhang; Prud'homme, Gerald J.

    2010-01-01

    GLP-1 has a variety of anti-diabetic effects. However, native GLP-1 is not suitable for therapy of diabetes due to its short half-life (t1/2168 h. Intraperitoneal glucose tolerance test (IPGTT) in mice showed that GLP-1/hIgG2 significantly decreased glucose excursion. Furthermore, IPGTT performed on mice one week after a single drug-injection also displayed significantly reduced glucose excursion, indicating that GLP-1/hIgG2 fusion protein has long-lasting effects on the modulation of glucose...

  13. Engineering a long-acting, potent GLP-1 analog for microstructure-based transdermal delivery.

    Science.gov (United States)

    Yang, Peng-Yu; Zou, Huafei; Chao, Elizabeth; Sherwood, Lance; Nunez, Vanessa; Keeney, Michael; Ghartey-Tagoe, Esi; Ding, Zhongli; Quirino, Herlinda; Luo, Xiaozhou; Welzel, Gus; Chen, Guohua; Singh, Parminder; Woods, Ashley K; Schultz, Peter G; Shen, Weijun

    2016-04-12

    Antidiabetic treatments aiming to reduce body weight are currently gaining increased interest. Exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist administered twice daily via s.c. injection, improves glycemic control, often with associated weight reduction. To further improve the therapeutic efficacy of exendin-4, we have developed a novel peptide engineering strategy that incorporates a serum protein binding motif onto a covalent side-chain staple and applied to the peptide to enhance its helicity and, as a consequence, its potency and serum half-life. We demonstrated that one of the resulting peptides, E6, has significantly improved half-life and glucose tolerance in an oral glucose tolerance test in rodents. Chronic treatment of E6 significantly decreased body weight and fasting blood glucose, improved lipid metabolism, and also reduced hepatic steatosis in diet-induced obese mice. Moreover, the high potency of E6 allowed us to administer this peptide using a dissolvable microstructure-based transdermal delivery system. Pharmacokinetic and pharmacodynamic studies in guinea pigs showed that a single 5-min application of a microstructure system containing E6 significantly improved glucose tolerance for 96 h. This delivery strategy may offer an effective and patient-friendly alternative to currently marketed GLP-1 injectables and can likely be extended to other peptide hormones.

  14. Two short-acting kappa opioid receptor antagonists (zyklophin and LY2444296) exhibited different behavioral effects from the long-acting antagonist norbinaltorphimine in mouse anxiety tests.

    Science.gov (United States)

    Huang, Peng; Yakovleva, Tatyana; Aldrich, Jane V; Tunis, Julia; Parry, Christopher; Liu-Chen, Lee-Yuan

    2016-02-26

    Prototypical long-acting kappa opioid receptor (KOPR) antagonists [e.g., norbinaltorphimine (norBNI)] have been reported to exert anxiolytic-like effects in several commonly used anxiety tests in rodents including the novelty-induced hypophagia (NIH) and elevated plus maze (EPM) tests. It remains unknown if the short-acting KOPR antagonists (e.g., zyklophin and LY2444296) have similar effects. In this study effects of zyklophin and LY2444296 (s.c.) were investigated in the NIH and EPM tests in mice 1h post-injection and compared with norBNI (i.p.) 48h post-administration. In the NIH test, zyklophin at 3 and 1mg/kg, but not 0.3mg/kg, or LY2444296 at 30mg/kg decreased the latency of palatable food consumption in novel cages, but had no effect in training cages, similar to norBNI (10mg/kg). Zyklophin at 3 or 1mg/kg increased or had a trend of increasing the amount of palatable food consumption in novel cages, with no effects in training cages, further indicating its anxiolytic-like effect, but norBNI (10mg/kg) and LY2444296 (30mg/kg) did not. In the EPM test, norBNI (10mg/kg) increased open arm time and % open arm entries or time, but zyklophin at all three doses and LY2444296 (30mg/kg) had no effects. In addition, zyklophin at 3mg/kg increased numbers of close and total arm entries on EPM, suggesting increased activity; however, norBNI and LY2444296 had no effects on close and total arm entries. Thus, all three KOPR antagonists had anxiolytic-like effects in the NIH test. However, only the long-acting one (norBNI), but not the short-acting ones (zyklophin and LY2444296), demonstrated anti-anxiety like effects in the EPM test. It remains to be investigated if the differences are due to the differences in their durations of action and/or pharmacodynamic properties.

  15. Olanzapine for the prevention and treatment of chronic nausea and chemotherapy-induced nausea and vomiting.

    Science.gov (United States)

    Navari, Rudolph M

    2014-01-05

    Olanzapine is an atypical antipsychotic agent of the thiobenzodiazepine class. It blocks multiple neurotransmitter receptors including dopaminergic at D1, D2, D3, D4 brain receptors, serotonergic at 5-HT2a, 5-HT2c, 5-HT3, 5-HT6 receptors, catecholamines at alpha1 adrenergic receptors, acetylcholine at muscarinic receptors, and histamine at H1 receptors. Olanzapine has five times the affinity for 5-HT2 receptors than D2 receptors and has been used to treat schizophrenia and delirium. Olanzapine's activity at multiple receptors, particularly at the D2, 5-HT2c, and 5-HT3 receptors which appear to be involved in nausea and emesis, has prompted its use in the treatment of nausea and vomiting refractory to standard antiemetics. Case reports and formal clinical trials have demonstrated its efficacy in the treatment of chronic nausea, the prevention of chemotherapy-induced nausea and emesis, and the treatment of breakthrough chemotherapy-induced nausea and emesis. Phase II and phase III clinical trials have demonstrated that there is a significant improvement in nausea when olanzapine is added to guideline directed prophylactic antiemetic agents 5-HT3 receptor antagonists and tachykinin NK1 receptor antagonists in patients receiving moderately or highly emetogenic chemotherapy Common side effects of olanzapine when used over a period of months include weight gain as well as an association with the onset of diabetes mellitus, but these effects have not been seen with short term use of daily doses of less than one week.

  16. Spectrum of binge eating symptomatology in patients treated with clozapine and olanzapine.

    Science.gov (United States)

    Theisen, F M; Linden, A; König, I R; Martin, M; Remschmidt, H; Hebebrand, J

    2003-01-01

    The authors explored the binge eating symptomatology in 74 patients receiving clozapine (N = 57) or olanzapine (N = 17), and compared body mass index (BMI, kg/m(2)) and weight gain in patients with and without binge eating symptomatology. Subjects who screened positively for binge eating were interviewed using a modified version of the Questionnaire on Eating and Weight Patterns (QEWP). Current BMIs were assessed cross-sectionally, BMIs at initiation of clozapine/olanzapine treatment retrospectively. Thirty-seven subjects (50%) screened positively. Taking clozapine and olanzapine together, 6/27 (22.2%) females and 3/47 (6.4%) males fulfilled criteria for binge eating disorder, 3/27 (11.1%) females and 2/47 (4.3%) males for bulimia nervosa. Patients who screened positively showed higher current BMIs (26.8 +/- 3.9 vs. 24.7 +/- 3.7 kg/m(2)) and higher BMI increments during clozapine/olanzapine treatment (3.9 +/- 3.1 vs. 2.6 +/- 3.4 kg/m(2)) than patients who screened negatively. We conclude that clozapine/olanzapine may induce binge eating and full blown eating disorders which may have predictive value for weight gain. For future research in this field we suggest a novel DSM-IV research classification "Medication-induced eating disorders".

  17. A comparative study of olanzapine versus asenapine in acute treatment of manic episode: A 3-week prospective study

    Directory of Open Access Journals (Sweden)

    Ajeet Sidana

    2014-01-01

    Full Text Available Introduction: Treatment of bipolar disorders has evolved over the years from conventional mood stabilizers to second-generation antipsychotics. Among the atypical antipsychotics, few have been approved by Food and Drug Administration as treatment of bipolar disorders. Aim: To study the efficacy and tolerability of olanzapine and asenapine in the acute treatment of bipolar disorder-manic episode in a 3-week randomized prospective study. Materials and Methods: A 3-week randomized, prospective, comparative, flexible doses of olanzapine (5-30 mg/day and asenapine (10-20 mg/day for acute treatment of bipolar disorder-current manic episode with or without psychotic symptoms in hospitalized patients. Results: The end-point reduction in mean score of Young Mania rating scale in the olanzapine group was 15.82 in comparison to 6.88 in the asenapine group. Mean score on clinical global impression for bipolar disorder and positive and negative syndrome scale was significantly less in the olanzapine group at the end of the study. 81.81% patients in olanzapine group and 17.60% patients in asenapine group had clinical response. There was significant average weight gain in the olanzapine group - 1.9 kg in comparison to 0.87 kg in asenapine group. Conclusion: The clinical response with olanzapine is significantly higher than the asenapine in the treatment of bipolar disorder-manic episode with or without psychotic symptoms. However, there is significant weight gain in olanzapine-treated patients.

  18. Reducing olanzapine-induced weight gain side effect by using betahistine: a study in the rat model.

    Science.gov (United States)

    Deng, Chao; Lian, Jiamei; Pai, Nagesh; Huang, Xu-Feng

    2012-09-01

    Olanzapine is effective at treating multiple domains of schizophrenia symptoms. However, it induces serious metabolic side effects. Antipsychotic drug's antagonistic affinity to histamine H₁ receptors has been identified as a main contributor for weight gain/obesity side effects. This study therefore investigated whether a combined treatment of betahistine (a H₁ receptor agonist and H₃ receptor antagonist) could reduce the body weight/obesity induced by olanzapine. Female Sprague Dawley rats were treated orally with olanzapine (1 mg/kg, t.i.d.) and/or betahistine (2.67 mg/kg, t.i.d.), or vehicle for two weeks. Rats treated with olanzapine exhibited significant body weight gain and increased food intake. Co-treatment of olanzapine with betahistine significantly prevented (-45%) weight gain and reduced feeding efficiency compared to sole olanzapine treatment. Betahistine treatment alone had no effect on weight gain and food intake. Olanzapine reduced locomotor activity, but not betahistine. These findings demonstrate that olanzapine-induced body weight gain can partially be reduced by co-treatment with betahistine. Betahistine has H₃ receptor antagonistic effects to increase histamine release, which may augment its direct agonistic effects on H₁ receptors. These findings have important implications for clinical trials using betahistine to control antipsychotic-induced obesity side effects.

  19. Prevalence and factors affecting use of long acting and permanent contraceptive methods in Jinka town, Southern Ethiopia: a cross sectional study.

    Science.gov (United States)

    Mekonnen, Getachew; Enquselassie, Fikre; Tesfaye, Gezahegn; Semahegn, Agumasie

    2014-01-01

    In Ethiopia, knowledge of contraceptive methods is high though there is low contraceptive prevalence rate. This study was aimed to assess prevalence and associated factors of long acting and permanent contraceptive methods in Jinka town, southern Ethiopia. Community based cross sectional survey was conducted to assess the prevalence and factors affecting long acting and permanent methods of contraceptives utilization from March to April 2008. Eight hundred child bearing age women were participated in the quantitative study and 32 purposively selected focus group discussants were participated in the qualitative study. Face to face interview was used for data collection. Data were analyzed by SPSS version 13.0 statistical software. Descriptive statistics and logistic regression were computed to analyze the data. The prevalence of long acting and permanent contraceptive method was 7.3%. Three fourth (76.1%) of the women have ever heard about implants and implant 28 (50%) were the most widely used method. Almost two third of women had intention to use long acting and permanent methods. Knowledge of contraceptive and age of women have significant association with the use of long acting and permanent contraceptive methods. The overall prevalence of long acting and permanent contraceptive method was low. Knowledge of contraceptive and age of women have significant association with use of long acting and permanent contraceptive. Extensive health information should be provided.

  20. Long-Acting PASylated Leptin Ameliorates Obesity by Promoting Satiety and Preventing Hypometabolism in Leptin-Deficient Lep(ob/ob) Mice.

    Science.gov (United States)

    Bolze, Florian; Morath, Volker; Bast, Andrea; Rink, Nadine; Schlapschy, Martin; Mocek, Sabine; Skerra, Arne; Klingenspor, Martin

    2016-01-01

    Body weight loss of Lep(ob/ob) mice in response to leptin is larger than expected from the reduction in energy intake alone, suggesting a thermogenic action of unknown magnitude. We exploited the superior pharmacological properties of a novel long-acting leptin prepared via PASylation to study the contribution of its anorexigenic and thermogenic effects. PASylation, the genetic fusion of leptin with a conformationally disordered polypeptide comprising 600 Pro/Ala/Ser (PAS) residues, provides a superior way to increase the hydrodynamic volume of the fusion protein, thus retarding kidney filtration and extending plasma half-life. Here a single PAS(600)-leptin injection (300 pmol/g) resulted in a maximal weight reduction of 21% 6 days after application. The negative energy balance of 300 kJ/(4 d) was driven by a decrease in energy intake, whereas energy expenditure remained stable. Mice that were food restricted to the same extent showed an energy deficit of only 220 kJ/(4 d) owing to recurring torpor bouts. Therefore, the anorexigenic effect of PAS(600)-leptin contributes 75% to weight loss, whereas the thermogenic action accounts for 25% by preventing hypometabolism. In a second experiment, just four injections of PAS(600)-leptin (100 pmol/g) administered in 5- to 6-day intervals rectified the Lep(ob/ob) phenotype. In total, 16 nmol of PAS(600)-leptin per mouse triggered a weight loss of 43% within 20 days and normalized hypothermia and glucose homeostasis as well as hepatic steatosis. The beneficial properties of PAS(600)-leptin are substantiated by a comparison with previous studies in which approximately 400 nmol (∼25-fold) unmodified leptin was mandatory to achieve similar improvements.

  1. Comparison of inhaled long-acting β-agonist and anticholinergic effectiveness in older patients with chronic obstructive pulmonary disease: a cohort study.

    Science.gov (United States)

    Gershon, Andrea; Croxford, Ruth; To, Teresa; Stanbrook, Matthew B; Upshur, Ross; Sanchez-Romeu, Paula; Stukel, Thérèse

    2011-05-03

    Chronic obstructive pulmonary disease (COPD), a largely preventable and manageable respiratory condition, affects an estimated 12% to 20% of adults. Long-acting inhaled β-agonists and anticholinergics have both been shown to improve COPD outcomes and are recommended for moderate to severe disease; however, little is known about their comparative effectiveness. To compare survival in older patients with COPD who initially receive inhaled long-acting β-agonists with that of patients who receive anticholinergics. Population-based, retrospective cohort study. Ontario, Canada. Patients aged 66 years or older (who carry the largest burden of COPD and for whom data were available) who met a validated case definition of COPD on the basis of health administrative data and were newly prescribed an inhaled long-acting β-agonist or a long-acting anticholinergic (but not both) between 2003 and 2007. Patients were followed for up to 5.5 years. The primary outcome was all-cause mortality. A total of 46 403 patients with COPD (mean age, 77 years; 49% women) were included. Overall mortality was 38.2%. Mortality was higher in patients initially prescribed a long-acting anticholinergic than in those initially prescribed a long-acting inhaled β-agonist (adjusted hazard ratio, 1.14 [95% CI, 1.09 to 1.19]). Rates of hospitalizations and emergency department visits were also higher in those initially prescribed a long-acting anticholinergic. Patients were classified as having COPD on the basis of health administrative records, which did not contain information about lung function. Older adults initially prescribed long-acting inhaled β-agonists for the management of moderate COPD seem to have lower mortality than those initially prescribed long-acting anticholinergics. Further research is needed to confirm these findings in younger patients and in a randomized, controlled trial. Government of Ontario, Canada.

  2. Long-acting GLP-1 analogs for the treatment of type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Vilsbøll, Tina; Knop, Filip K

    2008-01-01

    Type 2 diabetes mellitus is characterized by insulin resistance, impaired glucose-induced insulin secretion, and inappropriately elevated glucagon levels which eventually result in hyperglycemia. The currently available treatment modalities for type 2 diabetes are often unsatisfactory in getting...... for the treatment of type 2 diabetes has become available in the US (since October 2005) and in Europe (since May 2007): the incretin-based therapies. The incretin-based therapies fall into two different classes: (i) incretin mimetics, i.e. injectable peptide preparations with actions similar to the natural...... patients to glycemic goals, even when used in combination, and therefore many patients develop microvascular and macrovascular diabetic complications. Additionally, these treatment modalities are often limited by inconvenient dosage regimens and safety and tolerability issues, the latter including...

  3. Long-acting GLP-1 analogs for the treatment of type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Vilsbøll, Tina; Knop, Filip K

    2008-01-01

    Type 2 diabetes mellitus is characterized by insulin resistance, impaired glucose-induced insulin secretion, and inappropriately elevated glucagon levels which eventually result in hyperglycemia. The currently available treatment modalities for type 2 diabetes are often unsatisfactory in getting...... for the treatment of type 2 diabetes has become available in the US (since October 2005) and in Europe (since May 2007): the incretin-based therapies. The incretin-based therapies fall into two different classes: (i) incretin mimetics, i.e. injectable peptide preparations with actions similar to the natural...... patients to glycemic goals, even when used in combination, and therefore many patients develop microvascular and macrovascular diabetic complications. Additionally, these treatment modalities are often limited by inconvenient dosage regimens and safety and tolerability issues, the latter including...

  4. Novel GLP-1 fusion chimera as potent long acting GLP-1 receptor agonist.

    Directory of Open Access Journals (Sweden)

    Qinghua Wang

    Full Text Available GLP-1 has a variety of anti-diabetic effects. However, native GLP-1 is not suitable for therapy of diabetes due to its short half-life (t1/2168 h. Intraperitoneal glucose tolerance test (IPGTT in mice showed that GLP-1/hIgG2 significantly decreased glucose excursion. Furthermore, IPGTT performed on mice one week after a single drug-injection also displayed significantly reduced glucose excursion, indicating that GLP-1/hIgG2 fusion protein has long-lasting effects on the modulation of glucose homeostasis. GLP-1/hIgG2 was found to be effective in reducing the incidence of diabetes in multiple-low-dose streptozotocin-induced type 1 diabetes in mice. Together, the long-lasting bioactive GLP-1/hIgG2 retains native GLP-1 activities and thus may serve as a potent GLP-1 receptor agonist.

  5. Onset of efficacy and tolerability following the initiation dosing of long-acting paliperidone palmitate: post-hoc analyses of a randomized, double-blind clinical trial

    Directory of Open Access Journals (Sweden)

    Fu Dong-Jing

    2011-05-01

    Full Text Available Abstract Background Paliperidone palmitate is a long-acting injectable atypical antipsychotic for the acute and maintenance treatment of adults with schizophrenia. The recommended initiation dosing regimen is 234 mg on Day 1 and 156 mg on Day 8 via intramuscular (deltoid injection; followed by 39 to 234 mg once-monthly thereafter (deltoid or gluteal. These post-hoc analyses addressed two commonly encountered clinical issues regarding the initiation dosing: the time to onset of efficacy and the associated tolerability. Methods In a 13-week double-blind trial, 652 subjects with schizophrenia were randomized to paliperidone palmitate 39, 156, or 234 mg (corresponding to 25, 100, or 150 mg equivalents of paliperidone, respectively or placebo (NCT#00590577. Subjects randomized to paliperidone palmitate received 234 mg on Day 1, followed by their randomized fixed dose on Day 8, and monthly thereafter, with no oral antipsychotic supplementation. The onset of efficacy was defined as the first timepoint where the paliperidone palmitate group showed significant improvement in the Positive and Negative Syndrome Scale (PANSS score compared to placebo (Analysis of Covariance [ANCOVA] models and Last Observation Carried Forward [LOCF] methodology without adjusting for multiplicity using data from the Days 4, 8, 22, and 36 assessments. Adverse event (AE rates and relative risks (RR with 95% confidence intervals (CI versus placebo were determined. Results Paliperidone palmitate 234 mg on Day 1 was associated with greater improvement than placebo on Least Squares (LS mean PANSS total score at Day 8 (p = 0.037. After the Day 8 injection of 156 mg, there was continued PANSS improvement at Day 22 (p ≤ 0.007 vs. placebo and Day 36 (p Conclusions Significantly greater symptom improvement was observed by Day 8 with paliperidone palmitate (234 mg on Day 1 compared to placebo; this effect was maintained after the 156 mg Day 8 injection, with a trend towards a dose

  6. Prescribing of opioid analgesics and related mortality before and after the introduction of long-acting oxycodone

    Science.gov (United States)

    Dhalla, Irfan A.; Mamdani, Muhammad M.; Sivilotti, Marco L.A.; Kopp, Alex; Qureshi, Omar; Juurlink, David N.

    2009-01-01

    Introduction Opioid-related mortality appears to be increasing in Canada. We examined the true extent of the problem and the impact of the introduction of long-acting oxycodone. Methods We examined trends in the prescribing of opioid analgesics in the province of Ontario from 1991 to 2007. We reviewed all deaths related to opioid use between 1991 and 2004. We linked 3271 of these deaths to administrative data to examine the patients’ use of health care services before death. Using time-series analysis, we determined whether the addition of long-acting oxycodone to the provincial drug formulary in January 2000 was associated with an increase in opioid-related mortality. Results From 1991 to 2007, annual prescriptions for opioids increased from 458 to 591 per 1000 individuals. Opioid-related deaths doubled, from 13.7 per million in 1991 to 27.2 per million in 2004. Prescriptions of oxycodone increased by 850% between 1991 and 2007. The addition of long-acting oxycodone to the drug formulary was associated with a 5-fold increase in oxycodone-related mortality (p opioid-related mortality (p = 0.02). The manner of death was deemed unintentional by the coroner in 54.2% and undetermined in 21.9% of cases. Use of health care services in the month before death was common: for example, of the 3066 patients for whom data on physician visits were available, 66.4% had visited a physician in the month before death; of the 1095 patients for whom individual-level prescribing data were available, 56.1% had filled a prescription for an opioid in the month before death. Interpretation Opioid-related deaths in Ontario have increased markedly since 1991. A significant portion of the increase was associated with the addition of long-acting oxycodone to the provincial drug formulary. Most of the deaths were deemed unintentional. The frequency of visits to a physician and prescriptions for opioids in the month before death suggests a missed opportunity for prevention. PMID:19969578

  7. The long-acting GLP-1 derivative NN2211 ameliorates glycemia and increases beta-cell mass in diabetic mice

    DEFF Research Database (Denmark)

    Rolin, Bidda; Larsen, Marianne O; Gotfredsen, Carsten F;

    2002-01-01

    NN2211 is a long-acting, metabolically stable glucagon-like peptide-1 (GLP-1) derivative designed for once daily administration in humans. NN2211 dose dependently reduced the glycemic levels in ob/ob mice, with antihyperglycemic activity still evident 24 h postdose. Apart from an initial reduction...... for increased proliferation. In db/db mice, exendin-4 and NN2211 decreased blood glucose compared with vehicle, but NN2211 had a longer duration of action. Food intake was lowered only on day 1 with both compounds, and body weight was unaffected. beta-Cell proliferation rate and mass were significantly...

  8. Treatment of advanced pancreatic cancer with the long-acting somatostatin analogue lanreotide: in vitro and in vivo results

    Science.gov (United States)

    Raderer, M; Hamilton, G; Kurtaran, A; Valencak, J; Haberl, I; Hoffmann, O; Kornek, G V; Vorbeck, F; Hejna, M H L; Virgolini, I; Scheithauer, W

    1999-01-01

    Fourteen patients with metastatic pancreatic adenocarcinoma were treated with the long-acting somatostatin (SST) analogue lanreotide. No objective response was obtained, and the median survival was 4 months (range 1.8–7 months). Pancreatic cancer could not be visualized by means of SST-receptor (R) scintigraphy in our patients. In vitro data also demonstrated absence of SSTR2 expression, suggesting pancreatic cancer not to be a potential target for treatment with SST analogues. © 1999 Cancer Research Campaign PMID:10027326

  9. New developments in long-acting reversible contraception: the promise of intrauterine devices and implants to improve family planning services.

    Science.gov (United States)

    Turok, David K; Gawron, Lori M; Lawson, Samantha

    2016-11-01

    After decades of having the developed world's highest rates of unintended pregnancy, the United States finally shows signs of improvement. This progress is likely due in large part to increased use of highly effective long-acting reversible methods of contraception. These methods can be placed and do not require any maintenance to provide years of contraception as effective as sterilization. Upon removal, fertility returns to baseline rates. This article addresses advances in both software-improved use and elimination of barriers to provide these methods; and hardware-novel delivery systems and devices. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  10. Olanzapine induced biochemical and histopathological changes after its chronic administration in rats

    Directory of Open Access Journals (Sweden)

    Rehmat Shah

    2016-11-01

    Full Text Available Objective: Olanzapine is a second generation antipsychotic acting mainly as a dopamine D2 and serotonine 5-HT2 receptors antagonist prescribed in the treatment of schizophrenia and various other psychiatric illnesses. Even though olanzapine is widely used in psychiatry, its effects on the architecture of pancreas, liver and kidneys are little known. The histology of pancreas especially has never been studied. For these reasons, the current study was designed to elucidate the toxic effects of chronic administration of olanzapine on pancreas, liver and kidneys and the enzymes released by these tissues in an escalating dose manner. Methods: Fourteen male rats were divided into two groups equally, the olanzapine group and the controls. Olanzapine was administered in a dose of 5 mg/kg/d for the first eight weeks, 10 mg/kg/d for next four weeks and 15 mg/kg/d through the last two week period of 14 weeks experiment. The controls received acidified saline only. Both the groups received restricted diet (20 g/12 h. The body weight and level of random blood sugar (RBS were measured on a weekly basis. The levels of lipase, amylase, alanine transaminase (ALT and aspartate transaminase (AST were determined terminally. At the end of the experiment, the tissues were dissected out for histopathological evaluation. Results: Significant loss in body weight, change in the level of random blood sugar (∗∗P  0.05. The pancreas has shown derangement of beta cells and fibrotic growth. A mild to moderate focal increase in glomerular cellularity, cellular proliferation and glomerular capsules with negligible basement membranes were observed in the kidneys. No changes were observed in the architecture of the liver. Conclusion: The findings of this study indicated that the incidence of adverse effects associated with olanzapine could be prevented/alleviated/delayed by allowing restricted diet.

  11. RNA sequencing reveals a slow to fast muscle fiber type transition after olanzapine infusion in rats.

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    Christopher J Lynch

    Full Text Available Second generation antipsychotics (SGAs, like olanzapine, exhibit acute metabolic side effects leading to metabolic inflexibility, hyperglycemia, adiposity and diabetes. Understanding how SGAs affect the skeletal muscle transcriptome could elucidate approaches for mitigating these side effects. Male Sprague-Dawley rats were infused intravenously with vehicle or olanzapine for 24h using a dose leading to a mild hyperglycemia. RNA-Seq was performed on gastrocnemius muscle, followed by alignment of the data with the Rat Genome Assembly 5.0. Olanzapine altered expression of 1347 out of 26407 genes. Genes encoding skeletal muscle fiber-type specific sarcomeric, ion channel, glycolytic, O2- and Ca2+-handling, TCA cycle, vascularization and lipid oxidation proteins and pathways, along with NADH shuttles and LDH isoforms were affected. Bioinformatics analyses indicate that olanzapine decreased the expression of slower and more oxidative fiber type genes (e.g., type 1, while up regulating those for the most glycolytic and least metabolically flexible, fast twitch fiber type, IIb. Protein turnover genes, necessary to bring about transition, were also up regulated. Potential upstream regulators were also identified. Olanzapine appears to be rapidly affecting the muscle transcriptome to bring about a change to a fast-glycolytic fiber type. Such fiber types are more susceptible than slow muscle to atrophy, and such transitions are observed in chronic metabolic diseases. Thus these effects could contribute to the altered body composition and metabolic disease olanzapine causes. A potential interventional strategy is implicated because aerobic exercise, in contrast to resistance exercise, can oppose such slow to fast fiber transitions.

  12. Efficacy, tolerability and cost effectiveness of zotepine versus olanzapine in patients of acute schizophrenia

    Directory of Open Access Journals (Sweden)

    Saroj Kothari

    2013-10-01

    Full Text Available Background: Schizophrenia is a functional psychosis with severe personality changes and thought disorders without cerebral damage. No reports are available in literature regarding efficacy and tolerability of atypical antipsychotic drug zotepine over olanzapine a preferred drug worldwide for the treatment of schizophrenia. Therefore, present study is undertaken to evaluate efficacy, tolerability and cost effectiveness of zotepine over olanzapine in patients suffering from schizophrenia. Methods: A prospective, randomized, single blind, parallel, 6 weeks clinical study was conducted on a total of 112 patients, of schizophrenia attending psychiatry outpatient department at G. R. Medical College, Gwalior, India randomized into two groups (56 in each. Patients received either olanzapine (10-20mg or zotepine (75-150mg per day for a period of 6 week. Efficacy was measured by Positive and Negative Syndrome Scale (PANSS and Clinical Global Impression (CGI scale whereas tolerability was measured by dropout rate and frequency of adverse effects. Cost effectiveness was calculated in terms of cost incurred for improvement at the end of treatment period. Results: Both the drugs showed significant (P.0.05. Olanzapine showed significantly better (P0.05 between the two groups. Incidence of akathisia and drop out (16% and 23% with zotepine were significant (P<0.05 as compared to olanzapine (2% and 11% respectively. Conclusions: Though the efficacy of both the drugs is comparable, olanzapine appears to have better tolerability and cost effectiveness than zotepine in patients of schizophrenia. [Int J Basic Clin Pharmacol 2013; 2(5.000: 577-582

  13. Olanzapine as an antiemetic in refractory nausea and vomiting in advanced cancer.

    Science.gov (United States)

    Srivastava, Manish; Brito-Dellan, Norman; Davis, Mellar P; Leach, Marie; Lagman, Ruth

    2003-06-01

    Nausea and vomiting are difficult symptoms to manage in patients with advanced cancer. Several classes of antiemetics are available, including phenothiazines, butyrophenones, substituted benzamides and selective serotonin antagonists, as well as corticosteroids. Most patients will respond to either single agents or combinations that frequently include corticosteroids. A minority of patients will have nausea that fails to respond. The atypical antipsychotic, olanzapine, relieves nausea in some patients failing to respond to the usual antiemetics. Two case reports are presented and the rationale for olanzapine's benefit is discussed.

  14. [3-D ultrasound-assisted gait analysis of schizophrenic patients. Comparison between conventional neuroleptics and olanzapine].

    Science.gov (United States)

    Putzhammer, Albert; Heindl, Bernhard; Müller, Jürgen; Broll, Karin; Pfeiff, Liane; Perfahl, Maria; Hess, Linda; Koch, Horst

    2003-05-01

    Schizophrenic disorders as well as neuroleptic treatment can affect locomotion. The study assessed the influence of neuroleptic treatment on human gait via ultrasonic topometric gait analysis. In a control sample the test system proved high test-retest-reliability. Spatial and temporal gait parameters were assessed in schizophrenic patients without neuroleptic treatment (n = 12) and under treatment with conventional neuroleptics (n = 14) and re-assessed after treatment change to the atypical neuroleptic olanzapine in a repeated measures design. After switch from conventional neuroleptics to olanzapine patients showed an increase of gait velocity (p step length (p gait analysis.

  15. Corpus luteum development and function after supplementation of long-acting progesterone during the early luteal phase in beef cattle.

    Science.gov (United States)

    Pugliesi, G; Oliveria, M L; Scolari, S C; Lopes, E; Pinaffi, F V; Miagawa, B T; Paiva, Y N; Maio, J R G; Nogueira, G P; Binelli, M

    2014-02-01

    Strategic supplementation of P4 may be used to increase conception rates in cattle, but timing of supplementation in relation to ovulation, mass of supplementary P4 and formulation of the P4-containing supplement has not been determined for beef cattle. Effects of supplementation of long-acting progesterone (P4) on Days 2 or 3 post-ovulation on development, function and regression of corpus luteum (CL) were studied in beef cattle. Cows were synchronized with an oestradiol/P4-based protocol and treated with 150 or 300 mg of long-acting P4 on Day 2 or 3 post-ovulation (6-7 cows/group). Colour-doppler ultrasound scanning and blood sample collection were performed from Day 2-21.5. Plasma P4 concentrations were greater (p  0.05) among groups, suggesting no effect of P4 treatment on luteal development. The frequency of cows that began luteolysis before Day 15 was greater (p beef cattle. © 2013 Blackwell Verlag GmbH.

  16. Comparison of resource use by COPD patients on inhaled therapies with long-acting bronchodilators: a database study

    Directory of Open Access Journals (Sweden)

    Kozma Chris M

    2011-12-01

    Full Text Available Abstract Background The purpose of this analysis was to compare health care costs and utilization among COPD patients who had long-acting beta-2 agonist (LABA OR long-acting muscarinic antagonist (LAMA; LABA AND LAMA; or LABA, LAMA, AND inhaled corticosteroid (ICS prescription claims. Methods This was a 12 month pre-post, retrospective analysis using COPD patients in a national administrative insurance database. Propensity score and exact matching were used to match patients 1:1:1 between the LABA or LAMA (formoterol, salmeterol, or tiotropium, LABA and LAMA (tiotropium/formoterol or tiotropium/salmeterol, and LABA, LAMA and ICS (bronchodilators plus steroid groups. Post-period comparisons were evaluated with analysis of covariance. Costs were evaluated from a commercial payer perspective. Results A total of 523 patients were matched using 29 pre-period variables (e.g., demographics, medication exposure. Post-match assessments indicated balance among the cohorts. COPD-related costs differed among groups (LABA or LAMA $2,051 SE = 91; LABA and LAMA $2,823 SE = 62; LABA, LAMA and ICS $3,546 SE = 89; all p Conclusions Significant cost differences driven mainly by pharmaceuticals were observed among LABA or LAMA, LABA and LAMA and LABA, LAMA and ICS therapies. A COPD-related cost offset was observed from single bronchodilator to two bronchodilators. Addition of an ICS with two bronchodilators resulted in higher treatment costs without reduction in other COPD-related costs compared with two bronchodilators.

  17. Rural women are more likely to use long acting contraceptive in Tigray region, Northern Ethiopia: a comparative community-based cross sectional study.

    Science.gov (United States)

    Alemayehu, Mussie; Kalayu, Aster; Desta, Alem; Gebremichael, Hailay; Hagos, Tesfalem; Yebyo, Henock

    2015-09-04

    In the latest report of Ethiopian Demographic and Health Survey (EDHS) 2011, the maternal mortality ratio (MMR) was estimated at 676/100,000 live births, with total fertility rate at 4.8 and contraceptive prevalence rate at 29 %. Knowledge and utilization of long acting contraceptive in the Tigray region are low. This study aims at comparing and identifying factors related to the utilization of long acting contraceptive in urban versus rural settings of Ethiopia. A comparative community-based cross-sectional study, comprised of quantitative and qualitative methods, was conducted among 1035 married women in Wukro (urban area) and Kilteawlaelo district (rural area) in March, 2013. Stratified sampling technique was employed to approach the study participants. Data were analyzed using SPSS version 20. Multiple logistic regression analysis was used to identify the respective effect of independent predictors on utilization of long acting contraceptive. The proportion of long acting contraceptive use among the respondents was 19.9 % in the town of Wukro and 37.8 % in the district of Kilteawlaelo. Implanon was the most common type of contraceptive used in both districts, urban (75 %) and rural (94 %). The odds of using the long acting contraceptive method were three times higher among married women in the rural areas as compared with the urban women [AOR = 3. 30; 95 %, CI:2.17, 5.04]. No or limited support from male partners was an obstacle to using long acting contraceptive method [AOR = 0. 24, 95 of CI: 0.13, 0.44]. Moreover, married women whose partner did not permit them to use long acting contraceptive [AOR = 0. 47, 95 % of CI: 0.24, 0.92] and women who attended primary education [AOR = 0.24, 95 %, CI: 0.13, 0.44] were significantly associated with long acting contraceptive use. Overall, the proportion of long acting contraceptive use has found to be low. Rural women were more likely to use long acting contraceptives as compared to urban women

  18. Demand for long acting contraceptive methods and associated factors among family planning service users, Northwest Ethiopia: a health facility based cross sectional study.

    Science.gov (United States)

    Yalew, Saleamlak Adbaru; Zeleke, Berihun Megabiaw; Teferra, Alemayehu Shimeka

    2015-02-04

    Demand for long acting contraceptive methods is one of the key factors for total fertility rate and reproductive health issues. Increased demand for these methods can decline fertility rate through spacing and limiting family size in turn improving maternal and family health and socioeconomic development of a country. The aim of this study was to assess demand for long acting contraceptives and associated factors among family planning users in Debre-Tabor Town, Northwest Ethiopia. Facility based cross-sectional study was conducted from July to August 2013. Data was collected on 487 current family planning users through face to face interview using structured questionnaire. Study participants were selected by systematic sampling method. Data were entered in to Epi Info and analyzed by using SPSS version 20. Bi-variable and multi-variable regression analyses were done to identify factors associated with demand for long acting contraceptive methods. Odds ratio with 95% CI was used to assess the association between the independent variables and demand for long acting family planning methods. The study showed that, demand for long acting contraceptives was 17%. Only 9.2% of the women were using long acting contraceptive methods (met need). About 7.8% of women were using short acting methods while they actually want to use long acting methods (unmet need). Demand for LACMs was positively associated 3 with being a daily labour (AOR = 3.87, 95% CI = [1.06, 14.20]), being a student (AOR = 2.64, 95% CI = [1.27, 5.47]), no future birth intensions (AOR = 2.17, 95% CI = [1.12, 4.23]), having five or more children (AOR = 1.67, 95% CI = [1.58, 4.83]), deciding together with husbands for using the methods (AOR = 2.73, 95% CI = [1.40, 5.32]) and often having discussion with husband (AOR = 3.89, 95% CI = [1.98, 7.65]). Clients treated poorly by the health care providers during taking the services was negatively associated with demand for LACMs (AOR = 0.42, 95% CI = [0.24, 0

  19. Effect of long-acting testosterone undecanoate treatment on quality of life in men with testosterone deficiency syndrome: a double blind randomized controlled trial

    Institute of Scientific and Technical Information of China (English)

    Seng-Fah Tong; Chirk-Jenn Ng; Boon-Cheok Lee; Verna-KM Lee; Ee-Ming Khoo; Eng-Giap Lee; Hui-Meng Tan

    2012-01-01

    This study aimed to investigate the effect of intramuscular injection of testosterone undecanoate on overall quality of life (QoL) in men with testosterone deficiency syndrome (TDS).A randomized controlled trial over a 12-month period was carried out in 2009.One hundred and twenty men aged 40 years and above with a diagnosis of TDS (serum total testosterone < 12 nmol l-1 and total Aging Male Symptom (AMS) scores ≥ 27) were invited to participate.Interventions comprised intramuscular injection of either placebo or 1000 mg testosterone undecanoate,given at weeks 0,6,18,30 and 42.This paper presents the secondary analysis of QoL changes measured in the scores of Short-Form-12 (SF-12) scale at baseline,weeks 30 and 48 after the first injection.A total of 56/60 and 58/60 men from the active treatment and placebo group,respectively,completed the study.At week 48,before adjusting for baseline differences,the QoL of men in the treatment group improved significantly in five out of the eight domains on SF-12.The physical health composite scores improved 4.0 points from a baseline of 41.9±7.0 in the treatment group compared to 0.8 point from a baseline of 43.7±7.1 in the placebo group (F=3.652,P=0.027).The mental health composite scores improved 4.4 points from a baseline of 37.1±9.0 in the treatment group compared to 1.0 points from a baseline of 37.6±7.9 in the placebo group (F=4.514,P=0.018).After adjusting for baseline differences,significant improvement was observed in mental health composite scores,but not in physical health composite scores.Long-acting testosterone undecanoate significantly improved the mental health component of QoL in men with TDS.

  20. Expression and Characterization of a Potent Long-Acting GLP-1 Receptor Agonist, GLP-1-IgG2σ-Fc.

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    Yi Yang

    Full Text Available Human GLP-1 (glucagon-like peptide-1 can produce a remarkable improvement in glycemic control in patients with type 2 diabetes. However, its clinical benefits are limited by its short half-life, which is less than 2 min because of its small size and rapid enzymatic inactivation by dipeptidyl peptidase IV. We engineered GLP-1-IgG2σ-Fc, a 68-kDa fusion protein linking a variant human GLP-1 (A8G/G26E/R36G to a human IgG2σ constant heavy-chain. A stably transfected Chinese hamster ovary cell line was obtained using electroporation. Western blotting showed that the expressed protein was immunoreactive to both GLP-1 and IgG antibodies. GLP-1-IgG2σ-Fc stimulated insulin secretion from INS-1 cells in a dose- and glucose-dependent manner and increased insulin mRNA expression. The half-life of GLP-1-IgG2σ-Fc in cynomolgus monkeys was approximately 57.1 ± 4.5 h. In the KKAy mouse model of diabetes, one intraperitoneal injection of GLP-1-IgG2σ-Fc (1 mg/kg reduced blood glucose levels for 5 days. A 4-week repeat-administration study identified sustained effects on blood glucose levels. Oral glucose tolerance tests conducted at the beginning and end of this 4-week period showed that GLP-1-IgG2σ-Fc produced a stable glucose lowering effect. In addition, KKAy mice treated with GLP-1-IgG2σ-Fc showed statistically significant weight loss from day 23. In conclusion, these properties of GLP-1-IgG2σ-Fc demonstrated that it represented a potential long-acting GLP-1 receptor agonist for the treatment of type 2 diabetes.

  1. Does lower dose of long-acting triptorelin maintain pituitary suppression and produce good live birth rate in long down-regulation protocol for in-vitro fertilization?

    Science.gov (United States)

    Chen, Xin; Feng, Shu-xian; Guo, Ping-ping; He, Yu-xia; Liu, Yu-dong; Ye, De-sheng; Chen, Shi-ling

    2016-04-01

    The effects of pituitary suppression with one-third depot of long-acting gonadotropin-releasing hormone (GnRH) agonist in GnRH agonist long protocol for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) were investigated. A retrospective cohort study was performed on 3186 cycles undergoing IVF/ICSI with GnRH agonist long protocol in a university-affiliated infertility center. The pituitary was suppressed with depot triptorelin of 1.25 mg or 1.875 mg. There was no significant difference in live birth rate between 1.25 mg triptorelin group and 1.875 mg triptorelin group (41.2% vs. 43.7%). The mean luteinizing hormone (LH) level on follicle-stimulating hormone (FSH) starting day was significantly higher in 1.25 mg triptorelin group. The mean LH level on the day of human chorionic gonadotrophin (hCG) administration was slightly but statistically higher in 1.25 mg triptorelin group. There was no significant difference in the total FSH dose between the two groups. The number of retrieved oocytes was slightly but statistically less in 1.25 mg triptorelin group than in 1.875 mg triptorelin group (12.90±5.82 vs. 13.52±6.97). There was no significant difference in clinical pregnancy rate between the two groups (50.5% vs. 54.5%). It was suggested that one-third depot triptorelin can achieve satisfactory pituitary suppression and produce good live birth rates in a long protocol for IVF/ICSI.

  2. The metabolic effects of olanzapine and topiramate in rats and humans

    NARCIS (Netherlands)

    Evers, S.S.; van Dijk, G.; van Vliet, A.; Scheurink, A.J.W.

    2011-01-01

    In humans the anti-psychotic Olanzapine (OLZ) has negative side effects on metabolism: it causes weight gain and increases the risk of developing type 2 Diabetes. The anti-convulsant Topiramate (TPM) has the opposite effects: it reduces body weight and improves insulin sensitivity. Because of this,

  3. Open-label study of olanzapine in children with pervasive developmental disorder.

    NARCIS (Netherlands)

    Kemner, C.; Swinkels, S.H.N.; Jonge, M.J.A. de; Tuynman-Qua, H.G.; Engeland, H.M. van

    2002-01-01

    The effects of olanzapine on the symptomatology of children with pervasive developmental disorder with emphasis on problems of communication and the safety of the drug were investigated in a 3-month open-label, open-dosage study. Participating in the study were 25 children age 6 to 16 years with a d

  4. Microtitrimetric determination of a drug content of pharmaceuticals containing olanzapine in non-aqueous medium

    Directory of Open Access Journals (Sweden)

    KANAKAPURA BASAVAIAH

    2009-05-01

    Full Text Available Two simple, rapid, reliable and cost-effective methods based on titrimetry in non-aqueous medium are described for the determination of olanzapine in pharmaceuticals. In these methods, the drug dissolved in the glacial acetic acid was titrated with the acetous perchloric acid with visual and potentiometric end point detection, crystal violet being used as the indicator for visual titration. The methods are applicable over 1-15 mg range of olanzapine. The procedures were applied to determine olanzapine in pharmaceutical products and the results were found to be in a good agreement with those obtained by the reference method. Associated pharmaceutical materials did not interfere. The precision results, expressed by inter-day and intra-day relative standard deviation values, were satisfactory, higher than 2%. The accuracy was satisfactory as well. The methods proved to be suitable for the analysis of olanzapine in bulk drug and in tablets. The accuracy and reliability of the methods were further ascertained by recovery studies via a standard addition technique with percent recoveries in the range 97.51-103.7% with a standard deviation of less than 2%.

  5. The stress stability of olanzapine: studies of interactions with excipients in solid state pharmaceutical formulations.

    Science.gov (United States)

    Djordjević Filijović, Nataša; Antonijević, Milan D; Pavlović, Aleksandar; Vučković, Ivan; Nikolić, Katarina; Agbaba, Danica

    2015-03-01

    Stress stability testing represents an important part of the drug development process. It is used as an important tool for the identification of degradation products and degradation pathways, as well as for the assessment of changes in physical form of drug molecules. The impact of excipients on the stability of olanzapine confirms that levels of impurities and degradants are limiting parameters and are therefore used for stability evaluation. The major degradation product of olanzapine was identified as 2-methyl-5,10-dihydro-4H-thieno[2,3-b][1,5]benzodiazepine-4-one (III). The structure of III was determined by using LC-MS, IR and NMR. Compatibility and stress stability results demonstrated that tablet formulations of olanzapine are sensitive to temperature and moisture. In samples protected from moisture, the increase in concentration of III was shown to be highly temperature dependent and the degradation followed zero-order kinetics. In addition, studies of olanzapine with excipients and in formulated tablets revealed polymorphic phase changes in some samples, influenced by a combination of stress temperature and humidity conditions. Polymorphic transitions were monitored using x-ray powder diffraction (XRPD) analysis and exhibited no correlation between the phase change (appearance of a new polymorph) and the degradation process.

  6. Risperidone versus olanzapine in the acute treatment of Persistent Delusional Disorder: A retrospective analysis.

    Science.gov (United States)

    Kulkarni, Karishma; Arasappa, Rashmi; Prasad M, Krishna; Zutshi, Amit; Chand, Prabhat K; Murthy, Pratima; Philip, Mariamma; Muralidharan, Kesavan

    2017-07-01

    There is a dearth of prospective trials studying treatment response in Persistent Delusional Disorder (PDD) to guide clinical practice. Available retrospective data indicate good response to second-generation antipsychotics (SGAs). We selected the data of patients prescribed either olanzapine or risperidone from a retrospective chart review of PDD (n=455) at our centre. We compared the two groups olanzapine (n =86) versus risperidone (n =280) on dose, drug adherence, response and adverse effects. The two groups were comparable on socio-demographic and clinical characteristics of PDD. There was no statistically significant difference between the two groups on adherence (>80%) and response to treatment (>52% good response). Olanzapine was effective at lower mean chlorpromazine equivalents than risperidone. Logistic regression analysis identified shorter mean duration of illness, good adherence and absence of substance dependence as predictors of good response to both drugs. Our study indicates that acute PDD responds well to treatment with both risperidone and olanzapine, provided adherence can be ensured. In the absence of specific treatment guidelines and randomized controlled trials for PDD, our analysis reaffirms the efficacy of SGAs. Copyright © 2017. Published by Elsevier B.V.

  7. Olanzapine-induced Fos expression in the rat forebrain; cross-tolerance with haloperidol and clozapine

    NARCIS (Netherlands)

    Sebens, JB; Koch, T; Ter Horst, GJ; Korf, J

    1998-01-01

    Acute administration of the atypical antipsychotic drug olanzapine (5 mg kg(-1) i.p.) increased the number of Fos-positive cells moderately in the prefrontal cortex and the striatum; more pronounced were the effects in the nucleus accumbens, the lateral septum, the hypothalamic paraventricular nucle

  8. Olanzapine-Induced Mania in Bipolar Spectrum Disorder:A Case Report

    Directory of Open Access Journals (Sweden)

    Mehrdad Eftekhar

    2006-07-01

    Full Text Available Objective: To report the case of a 46-year old male with major depressive disorder, who represented manic symptoms, when olanzapine was added to his treatment. Method: A 46-year old female, with a diagnosis of treatment resistant depression was referred to the authors. He had past history of depression for more than 20 years. The symptoms were present nearly every day since 1981, without any distinct period of remission, nor any noticeable fluctuation. His irritability had been disruptive to his family all these years. His doctor had prescribed maprotiline 25 mg/day, and lorazepam, 2mg/day, in addition to fluoxetine for the last 5 months. He is also a father of two children with methylphenidateresistant and sodium valproate-responsive attention-deficit hyperactivity disorder. Considering the antidepressant effects of olanzapine and its positive effects on irritability, the authors added olanzapine, to the patient’s previous medications. Results: After one week, he showed new problems such as talkativeness and beginning to smoke for the first time in his life, elevated mood, grandiosity about his intelligence and abilities, talkativeness, and shopping sprees. The score on the mania rating scale was 14. Fluoxetine was discontinued and sodium valproate, were prescribed. It took around 2 months to completely control the manic symptoms. Conclusions: In the patients with depression who show bipolar spectrum disorder features, adding mood stabilizers may be preferred to the drugs as olanzapine which could induce mania.

  9. Olanzapine-induced cerebral metabolic changes related to symptom improvement in schizophrenia.

    Science.gov (United States)

    Molina, Vicente; Gispert, Juan D; Reig, Santiago; Pascau, Javier; Martínez, Raúl; Sanz, Javier; Palomo, Tomás; Desco, Manuel

    2005-01-01

    The pattern of brain metabolic changes produced by olanzapine has yet to be described, despite the theoretical and clinical interest of this new antipsychotic. We studied a group of 17 schizophrenic patients who underwent two fluoro-deoxyglucose-positron emission tomography (FDG-PET) studies under two different conditions: a baseline scan during treatment with either conventional antipsychotics (n=15) or risperidone (n=2) and a second scan performed 17-24 weeks after switching to olanzapine. PET scans were obtained while performing a standard cognitive paradigm (Continuous Performance Test) and analysed by means of Statistical Parametric Mapping. No significant metabolic changes were found in the comparison between pre- and post-olanzapine conditions. A brain map of the statistical power of our design showed that changes up to 3% in the frontal and up to 8% in the occipital region were not likely to exist (1-beta=0.8). The degree of improvement in positive symptoms was related to the amount of activity decrease in the right orbital region and to the amount of activity increase in the primary visual area. Improvement in negative symptoms was associated with an activity increase in the dorsal prefrontal cortex, and a higher baseline activity in both temporal poles. These correlation patterns suggest that the functional mechanism of action of olanzapine may share traits from both typical and atypical neuroleptics.

  10. Olanzapine-induced weight gain: lessons learned from developing rat models

    NARCIS (Netherlands)

    van der Zwaal, E.M.

    2011-01-01

    Olanzapine is an effective and commonly prescribed antipsychotic drug, used for the treatment of schizophrenia and bipolar disorder. Unfortunately significant weight gain is a common side effect. In order to effectively address this side effect, it is crucial to gain insight into the underlying mech

  11. Olanzapine orally-disintegrating tablet in severe psychotic agitation: a naturalistic study.

    Science.gov (United States)

    Pascual, J C; Pérez, V; Martín, J L R; Safont, G; Puigdemont, D; Alvarez, E

    2007-01-01

    This study was conducted to determine effectiveness and safety of olanzapine in patients with severe agitation. A naturalistic, open-label study in 80 acutely agitated psychotic patients visited in our psychiatric emergency department. Patients received either a 20-mg olanzapine orally-disintegrating tablet or conventional treatment depending on attending psychiatrist's preference. Efficacy was assessed by the Excitement Component of the Positive and Negative Syndrome Scale (PANSS-EC), the Agitation-Calmness Evaluation Scale (ACES) and pragmatic variables (second pharmacological intervention and need for physical restraints). 60 % patients completed a 6 hour trial. Both groups showed a significant reduction in mean PANSS-EC score. The olanzapine-treated group showed statistically significant improvements: PANSS-EC (F=122.9; df=2.4; p=0.000), ACES (F=68.2; df=2.8; p=0.000). Treatment was well-tolerated and no serious side-effects were observed. In this naturalistic study in patients with severe agitation, 20-mg oral olanzapine was effective, rapid and safe.

  12. Influence of olanzapine on QT variability and complexity measures of heart rate in patients with schizophrenia.

    Science.gov (United States)

    Bär, Karl-Jürgen; Koschke, Mandy; Berger, Sandy; Schulz, Steffen; Tancer, Manuel; Voss, Andreas; Yeragani, Vikram K

    2008-12-01

    Previous studies have shown that untreated patients with acute schizophrenia present with reduced heart rate variability and complexity as well as increased QT variability. This autonomic dysregulation might contribute to increased cardiac morbidity and mortality in these patients. However, the additional effects of newer antipsychotics on autonomic dysfunction have not been investigated, applying these new cardiac parameters to gain information about the regulation at sinus node level as well as the susceptibility to arrhythmias. We have investigated 15 patients with acute schizophrenia before and after established olanzapine treatment and compared them with matched controls. New nonlinear parameters (approximate entropy, compression entropy, fractal dimension) of heart rate variability and also the QT-variability index were calculated. In accordance with previous results, we have observed reduced complexity of heart rate regulation in untreated patients. Furthermore, the QT-variability index was significantly increased in unmedicated patients, indicating increased repolarization lability. Reduction of the heart rate regulation complexity after olanzapine treatment was seen, as measured by compression entropy of heart rate. No change in QT variability was observed after treatment. This study shows that unmedicated patients with acute schizophrenia experience autonomic dysfunction. Olanzapine treatment seems to have very little additional impact in regard to the QT variability. However, the decrease in heart rate complexity after olanzapine treatment suggests decreased cardiac vagal function, which may increase the risk for cardiac mortality. Further studies are warranted to gain more insight into cardiac regulation in schizophrenia and the effect of novel antipsychotics.

  13. Olanzapine-high potency antipsychotic drug inducing significant weight gain: A case report

    Directory of Open Access Journals (Sweden)

    Marić Nađa P.

    2008-01-01

    Full Text Available INTRODUCTION Olanzapine is a second generation antipsychotic (SGA with a high level of therapeutic effectiveness in schizophrenia and other psychotic disorders. Along with the positive therapeutic effects, an increase of the body weight frequently occurs. According to the literature, the average weight gain is about 6-7 kg during several months of treatment. This could be valued as a moderate weight increase. CASE OUTLINE This article presents a case of a young female with schizophrenia, without clinical improvement with several antipsychotics (clozapine, risperidone, haloperidol and with the occurrence of significant neurological side effects. The treatment started with olanzapine (baseline was associated with good initial response (PANSS reduction 20% in the first two weeks and the improvement was maintained further on (PANSS reduction 50% after 16 weeks. Significant increase (20 kg, 40% in weight appeared during the following 16 weeks (BMI at baseline 17.9 kg/m2; BMI 16 weeks later 25.1 kg/m2. CONCLUSION High effectiveness of olanzapine in schizophrenia symptoms reduction was accompanied by a significant weight gain. However, this drug leads to impaired glucoregulation, dyslipidaemia etc. It also increases the risk of diabetes and cardio-vascular diseases, i.e. the main causes of mortality in schizophrenia after a suicide. Therefore, clinicians are suggested to focus on possible predictors of weight gain during olanzapine therapy, and act accordingly in order to prevent serious health consequences.

  14. Role of Polymeric Excipients in the Stabilization of Olanzapine when Exposed to Aqueous Environments

    Directory of Open Access Journals (Sweden)

    Maria Paisana

    2015-12-01

    Full Text Available Hydrate formation is a phase transition which can occur during manufacturing processes involving water. This work considers the prevention of hydration of anhydrous olanzapine and hydrate conversions in the presence of water and polymers (polyethyleneglycol; hydroxypropylcellulose; polyvinylpyrrolidone in forming pellets by wet extrusion and spheronisation. Anhydrous olanzapine was added to water with or without those polymers prior to extrusion with microcrystalline cellulose. Assessment of olanzapine conversion was made by XRP-Diffraction; FTIR spectroscopy; calorimetry (DSC and microscopy (SEM for crystal size and shape. The addition of water converted the anhydrous form into dihydrate B and higher hydrate; whereas polyethyleneglycol promoted a selective hydrate conversion into the higher hydrate olanzapine form. Both polyvinylpyrrolidone and hydroxypropylcellulose prevented the hydrate transformations of the anhydrous drug; the latter even in the presence of hydrate seeds. This may be explained by the higher H-bond ability; higher network association and higher hydrophobicity of hydroxypropylcellulose by comparison with polyethyleneglycol and polyvinylpyrrolidone; which could contribute to its higher affinity to the crystal surfaces of the hydrate nuclei/initial crystals and promoting steric hindrance to the incorporation of other drug molecules into the crystal lattice; thus, preventing the crystal growth. The addition of microcrystalline cellulose needed for the pellets production (final product did not eliminate the protector effect of both hydroxypropylcellulose and polyvinylpyrrolidone during pellets’ processing and dissolution evaluation.

  15. Open-label study of olanzapine in children with pervasive developmental disorder.

    NARCIS (Netherlands)

    Kemner, C.; Swinkels, S.H.N.; Jonge, M.J.A. de; Tuynman-Qua, H.G.; Engeland, H.M. van

    2002-01-01

    The effects of olanzapine on the symptomatology of children with pervasive developmental disorder with emphasis on problems of communication and the safety of the drug were investigated in a 3-month open-label, open-dosage study. Participating in the study were 25 children age 6 to 16 years with a

  16. Olanzapine-induced weight gain: lessons learned from developing rat models

    NARCIS (Netherlands)

    van der Zwaal, E.M.

    2011-01-01

    Olanzapine is an effective and commonly prescribed antipsychotic drug, used for the treatment of schizophrenia and bipolar disorder. Unfortunately significant weight gain is a common side effect. In order to effectively address this side effect, it is crucial to gain insight into the underlying

  17. The role of hypothalamic pathways in the metabolic side effects of Olanzapine

    NARCIS (Netherlands)

    Girault, E.M.

    2013-01-01

    Atypical antipsychotic drugs such as Olanzapine (Ola) induce weight gain and metabolic changes associated with the development of type 2 diabetes. The mechanisms underlying these undesired side effects are currently unknown. In this thesis, we showed that both acute and chronic administration of Ola

  18. Improving Access to Long-Acting Contraceptive Methods and Reducing Unplanned Pregnancy Among Women with Substance Use Disorders.

    Science.gov (United States)

    Black, Kirsten I; Day, Carolyn A

    2016-01-01

    Much has been written about the consequences of substance use in pregnancy, but there has been far less focus on the prevention of unintended pregnancies in women with substance use disorders (SUDs). We examine the literature on pregnancy incidence for women with SUDs, the clinical and economic benefits of increasing access to long-acting reversible contraceptive (LARC) methods in this population, and the current hurdles to increased access and uptake. High rates of unintended pregnancies and poor physical and psychosocial outcomes among women with SUDs underscore the need for increased access to, and uptake of, LARC methods among these women. A small number of studies that focused on improving access to contraception, especially LARC, via integrated contraception services predominantly provided in drug treatment programs were identified. However, a number of barriers remain, highlighting that much more research is needed in this area.

  19. Quantitative determination of amorphous nicardipine hydrochloride in long acting formula (NIC-LA) using light anhydrous silicic acid.

    Science.gov (United States)

    Kohinata, Takeru; Fujii, Mitsuo; Nakamura, Souichiro; Hamada, Noritaka; Yonemochi, Etsuo; Terada, Katsuhide

    2004-12-01

    We investigated a method to quantitatively determine amorphous nicardipine hydrochloride (NIC) in the NIC-long acting formula (LA) model formulas prepared using NIC, light anhydrous silicic acid (LASA) and carboxymethylethylcellulose (CMEC). Consequently, since the quantity of total NIC in the formula can be determined by means of HPLC and crystal NIC can be determined by the differential scanning calorimetry (DSC) method because the heat of fusion (85.08 J/g) of NIC is constant and unaffected by excipients, we developed the HPLC-DSC method by which the quantity of amorphous NIC is calculated as the difference between the quantity of total NIC determined by HPLC and the quantity of crystal NIC determined by DSC. This practical HPLC-DSC method was confirmed to have good accuracy and reproducibility.

  20. PHARMACOKINETIC EVALUATION OF A LONG-ACTING FENTANYL SOLUTION AFTER TRANSDERMAL ADMINISTRATION IN HELMETED GUINEAFOWL (NUMIDA MELEAGRIS).

    Science.gov (United States)

    Waugh, Lynnette; Knych, Heather; Cole, Gretchen; D'Agostino, Jennifer

    2016-06-01

    The objective of this study was to investigate the pharmacokinetics of a long-acting fentanyl solution in helmeted guineafowl ( Numida meleagris ) after transdermal administration. Twenty-one guineafowl received a single administration of 5 mg/kg of fentanyl transdermal solution. No adverse effects on behavior were appreciated. Plasma fentanyl concentrations were determined by liquid chromatography-mass spectrometry analysis of protein-precipitated samples. Mean maximum plasma concentration was 228.8 ng/ml at 4 hr. The mean plasma terminal half-life was 33.2 hr. At 168 hr the mean plasma concentration was 1.3 ng/ml. A single topical dose of 5 mg/kg appears to be safe for use in this species and maintained plasma concentrations above those reported to be analgesic in dogs for at least 7 days.

  1. The safety of long-acting ß2-agonists in the treatment of stable chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Decramer ML

    2013-01-01

    Full Text Available Marc L Decramer,1 Nicola A Hanania,2 Jan O Lötvall,3 Barbara P Yawn41Respiratory Division, University Hospital, KU Leuven, Belgium; 2Section of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, Houston, TX, USA; 3Krefting Research Centre, University of Gothenburg, Gothenburg, Sweden; 4Department of Research, Olmsted Medical Center, Rochester, MN, USABackground: Inhaled long-acting bronchodilators are the mainstay of pharmacotherapy for chronic obstructive pulmonary disease (COPD. Both the twice-daily long-acting ß2-adrenoceptor agonists (LABAs salmeterol and formoterol and the once-daily LABA indacaterol are indicated for use in COPD. This review examines current evidence for the safety of LABAs in COPD, focusing on their effect on exacerbations and deaths.Methods: We searched PubMed for placebo-controlled studies evaluating long-term (≥24 weeks use of formoterol, salmeterol, or indacaterol in patients with stable COPD, published between January 1990 and September 2012. We summarized data relating to exacerbations and adverse events, particularly events related to COPD.Results: From 20 studies examined (8774 LABA-treated patients, there was no evidence of an association between LABA treatment and increased exacerbations, COPD-related adverse events, or deaths. Where analyzed as an efficacy outcome, LABA treatment was generally associated with significant or numerical reductions in COPD exacerbations compared with placebo. Incidences of COPD-related adverse events were similar for active and placebo treatments. The incidence of adverse events typically associated with the ß2-agonist drug class such as skeletal muscle tremors and palpitations was low (often <1% of patients, and there were no reports of increased incidence of cardiac arrhythmias. The systemic effects of ß2-adrenoceptor stimulation, such as high glucose and potassium levels, were considered minor.Conclusion: Current evidence from clinical studies of the

  2. Cost effectiveness of olanzapine in prevention of affective episodes in bipolar disorder in the United Kingdom.

    Science.gov (United States)

    McKendrick, J; Cerri, K H; Lloyd, A; D'Ausilio, A; Dando, S; Chinn, C

    2007-08-01

    This study evaluated the cost effectiveness of olanzapine compared with lithium as maintenance therapy for patients with bipolar I disorder (BP1) in the UK. A Markov model was developed to assess costs and outcomes from the perspective of the UK National Health Service over a 1-year period. Patients enter the model after stabilization of a manic episode and are then treated with olanzapine or lithium. Using the findings of a recent randomized clinical trial, the model considers the monthly risk of manic or depressive episodes and of dropping out from allocated therapy. health care resources associated with acute episodes were derived primarily from a recent UK chart review. Costs of maintenance therapy and monitoring were also considered. Key factors influencing cost effectiveness were identified and included in a stochastic sensitivity analysis. The model estimated that, compared to lithium, olanzapine significantly reduced the annual number of acute mood episodes per patient from 0.81 to 0.58 (difference -0.23; 95% CI: -0.34, -0.12). Per patient average annual care costs fell by 799 UK pounds (95% CI: - 1,824 UK pounds, 59 UK pounds) driven by reduced inpatient days--but the cost difference was not statistically significant. Sensitivity analysis found the results to be robust to plausible variation in the model's parameters. The model estimated that using olanzapine instead of lithium as maintenance therapy for BP1 would significantly reduce the rate of acute mood events resulting in reduced hospital costs. Based on available evidence, there is a high likelihood that olanzapine would reduce costs of care compared to lithium.

  3. Midazolam-Droperidol, Droperidol, or Olanzapine for Acute Agitation: A Randomized Clinical Trial.

    Science.gov (United States)

    Taylor, David McD; Yap, Celene Y L; Knott, Jonathan C; Taylor, Simone E; Phillips, Georgina A; Karro, Jonathan; Chan, Esther W; Kong, David C M; Castle, David J

    2017-03-01

    We aim to determine the most efficacious of 3 common medication regimens for the sedation of acutely agitated emergency department (ED) patients. We undertook a randomized, controlled, double-blind, triple-dummy, clinical trial in 2 metropolitan EDs between October 2014 and August 2015. Patients aged 18 to 65 years and requiring intravenous medication sedation for acute agitation were enrolled and randomized to an intravenous bolus of midazolam 5 mg-droperidol 5 mg, droperidol 10 mg, or olanzapine 10 mg. Two additional doses were administered, if required: midazolam 5 mg, droperidol 5 mg, or olanzapine 5 mg. The primary outcome was the proportion of patients adequately sedated at 10 minutes. Three hundred forty-nine patients were randomized to the 3 groups. Baseline characteristics were similar across the groups. Ten minutes after the first dose, significantly more patients in the midazolam-droperidol group were adequately sedated compared with the droperidol and olanzapine groups: differences in proportions 25.0% (95% confidence interval [CI] 12.0% to 38.1%) and 25.4% (95% CI 12.7% to 38.3%), respectively. For times to sedation, the differences in medians between the midazolam-droperidol group and the droperidol and olanzapine groups were 6 (95% CI 3 to 8) and 6 (95% CI 3 to 7) minutes, respectively. Patients in the midazolam-droperidol group required fewer additional doses or alternative drugs to achieve adequate sedation. The 3 groups' adverse event rates and lengths of stay did not differ. Midazolam-droperidol combination therapy is superior, in the doses studied, to either droperidol or olanzapine monotherapy for intravenous sedation of the acutely agitated ED patient. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  4. Ziprasidone versus olanzapine, risperidone or quetiapine in patients with chronic schizophrenia: a 12-week open-label, multicentre clinical trial

    DEFF Research Database (Denmark)

    Lublin, Henrik; Haug, Hans-Joachim; Koponen, Hannu

    2009-01-01

    The efficacy, safety and tolerability of ziprasidone versus the comparators olanzapine, risperidone or quetiapine were investigated in adult patients with chronic schizophrenia, schizoaffective and schizophreniform disorders, with lack of efficacy or intolerance to their previous antipsychotic tr...

  5. Effect of olanzapine or fluoxetine and combined olanzapine with fluoxetine on citrate synthase activity in rat brain%奥氮平与氟西汀单独或联合给药对大鼠脑内柠檬酸合成酶活性的影响

    Institute of Scientific and Technical Information of China (English)

    张普; 孔丽敏

    2016-01-01

    目的:研究奥氮平与氟西汀单独或两药联合给药对大鼠脑内柠檬酸合成酶活性短期和长期的影响。方法135只Wistar大鼠随机分为对照组与实验组。对照组腹腔注射生理盐水,实验组再分为几个亚组。2个剂量奥氮平组(3,6 mg· kg-1),2个剂量氟西汀组(12.5,25.0 mg· kg-1),联合用药组:A组(3 mg· kg-1奥氮平+12.5 mg · kg-1氟西汀)、B 组(3 mg · kg-1奥氮平+25.0 mg· kg-1氟西汀)、C组(6 mg· kg-1奥氮平+12.5 mg · kg -1氟西汀)、D组(6 mg· kg-1奥氮平+25.0 mg· kg-1氟西汀),连续给药28 d。用分光光度法测定并比较第1次给药后2 h、末次给药后2,24 h的大鼠前额叶皮层、海马区和纹状体柠檬酸合成酶的活性。结果与对照组相比,在给药第1次后2 h,2个剂量奥氮平组、大剂量氟西汀组、联合A组的大鼠海马区柠檬酸合成酶活性明显增加( P<0.05)。结论短程小剂量奥氮平联合氟西汀可显著增加大鼠脑内柠檬酸合成酶活性。%Objective To evaluated the effect of acute and chronic ad-ministration of fluoxetine , olanzapine and the combination of fluoxetine/olanzapine on citrate synthase activity in rat brain.Methods One hun-dred and thirty-five Wistar rats were randomly divided into control group and experimental group.The rats of the control group received injections of saline.The rats of the experimental group were divided into 8 sub groups by the ways of treament:low and high dose of olanzapine groups (3,6 mg· kg -1 ),the low and high dose of fluoxetine groups (12.5,25.0 mg· kg-1 ), the two -drug combination:A group(3 mg· kg -1 olanza-pine +12.5 mg· kg -1 fluoxetine), B group(3 mg· kg -1 olanzapine +25 mg · kg -1 fluoxetine ) , C group ( 6 mg · kg -1 olanzapine +12.5 mg· kg-1 fluoxetine), D group(6 mg· kg -1 olanzapine +25 mg· kg -1 fluoxetine ).Saline or medications were given once a day , which lasted

  6. Enhancing the aqueous solubility and dissolution of olanzapine using freeze-drying

    Directory of Open Access Journals (Sweden)

    Mudit Dixit

    2011-12-01

    Full Text Available The aim of the present study was to develop an olanzapine freeze-dried tablet (FDT. The solubility and dissolution rate of poorly water-soluble olanzapine was improved by preparing a freeze-dried tablet of olanzapine using the freeze-drying technique . The FDT was prepared by dispersing the drug in an aqueous solution of highly water-soluble carrier materials consisting of gelatin, glycine, and sorbitol. The mixture was poured in to the pockets of blister packs and then was subjected to freezing and lyophilisation. The FDT was characterised by DSC, XRD and SEM and was evaluated for saturation solubility and dissolution. The samples were stored in a stability chamber to investigate their physical stability. Results obtained by DSC and X-ray were analysed and showed the crystalline state of olanzapine in FDT transformation to the amorphous state during the formation of FDT. Scanning electron microscope (SEM results suggest reduction in olanzapine particle size. The solubility of olanzapine from the FDT was observed to be nearly four and a half times greater than the pure drug. Results obtained from dissolution studies showed that olanzapine FDT significantly improved the dissolution rate of the drug compared with the physical mixture (PM and the pure drug. More than 90% of olanzapine in FDT dissolved within 5 minutes, compared to only 19.78% of olanzapine pure drug dissolved over the course of 60 minutes. In a stability test, the release profile of the FDT was unchanged, as compared to the freshly prepared FDT after 90 days of storing.O objetivo do presente estudo foi desenvolver comprimidos liofilizados de olanzapina (FDT. A solubilidade e a taxa de dissolução da olanzapina, fracamente solúvel em água, foram melhoradas com a preparação de comprimidos liofilizados de olanzapina usando a técnica de liofilização. O FDT foi preparado por dispersão do fármaco em solução aquosa de materiais altamente solúveis em água, como gelatina

  7. Darbepoetin alpha, a long-acting erythropoeitin derivate, does not alter LPS evoked myocardial depression and gene expression of Bax, Bcl-Xs, Bcl-XL, Bcl-2, and TNF-alpha.

    Science.gov (United States)

    Brendt, Peter; Frey, Ulrich; Adamzik, Michael; Schäfer, Simon T; Peters, Jürgen

    2009-01-01

    Darbepoetin alpha (DA), a long-acting erythropoietin derivative stimulating erythropoiesis, can, by antiapoptotic effects, mitigate myocardial I/R injury. We tested the hypothesis that DA treatment improves left ventricular function (LV) in LPS evoked cardiomyopathy and alters gene expression of apoptosis-regulating proteins (Bcl-XL, Bcl-2, Bax, and Bcl-Xs) and TNF-alpha. In a prospective, controlled, randomized study in Lewis rats (n = 56; 8 groups), myocardial depression was evoked by LPS administration (serotype O127:B8; 10 mg/kg, i.p.). Darbepoetin alpha or vehicle was injected either 24 h before (pretreatment) or 2 h after LPS injection (treatment). Hearts were isolated 8 h after LPS injection, perfused (Krebs-Henseleit solution) in a Langendorff apparatus, and LV developed pressure and its derivatives were measured. For gene expression analysis, real-time polymerase chain reaction of LV specimen was performed. LPS decreased LV developed pressure (-64.6 +/- 7.9 mmHg) and its derivates by more than 60% in comparison to vehicle (P Xs, Bax, and TNF-alpha, but this was not altered by DA pretreatment. Furthermore, there was no effect on Bcl-Xl and Bcl-2 expression by DA alone. Whereas proapoptotic genes of the myocardium are up-regulated in LPS-induced cardiomyopathy, neither DA pretreatment nor treatment has significant effects on LV function or gene expression. This may suggest cardiac resistance to darbepoetin in LPS-mediated sepsis.

  8. Olanzapine Prevents the PCP-induced Reduction in the Neurite Outgrowth of Prefrontal Cortical Neurons via NRG1.

    Science.gov (United States)

    Zhang, Qingsheng; Yu, Yinghua; Huang, Xu-Feng

    2016-01-19

    Accumulating evidence suggests that reducing neurite outgrowth and synaptic plasticity plays a critical role in the pathology of cognitive deficits in schizophrenia. The N-methyl-D-aspartate receptor antagonist phencyclidine (PCP) can induce symptoms of schizophrenia as well as reduce dendritic spine density and neurite growth. The antipsychotic drug olanzapine may improve these deficits. This study aimed to investigate: (1) if olanzapine prevents PCP-induced suppression of neurite outgrowth and synaptic protein expression; (2) if olanzapine affects the Akt-GSK3 signaling pathway; and (3) the role of neuregulin 1 (NRG1) in this process. Immunofluorescence revealed that PCP treatment for 24 hours reduces both neurite length (28.5%) and the number of neurite branches (35.6%) in primary prefrontal cortical neuron cultures. PCP reduced protein and mRNA expressions of synaptophysin (24.9% and 23.2%, respectively) and PSD95 (31.5% and 21.4%, respectively), and the protein expression of p-Akt (26.7%) and p-GSK3β (35.2%). Olanzapine co-treatment prevented these PCP-induced effects in normal neurons but not in neurons from NRG1-knockout mice. These results indicate that NRG1 mediates the preventive effects of olanzapine on the PCP-induced impairment of neurite outgrowth and synaptic protein expression. This study provides potential targets for interventions on improving the efficacy of olanzapine on preventing cognitive deficits in schizophrenia.

  9. Sulpiride augmentation of olanzapine in the management of treatment-resistant chronic schizophrenia: evidence for improvement of mood symptomatology.

    Science.gov (United States)

    Kotler, Moshe; Strous, Rael D; Reznik, Ilya; Shwartz, Sima; Weizman, Abraham; Spivak, Baruch

    2004-01-01

    Several recent studies, albeit limited in sample number, design and generalizability, have suggested that augmentation of atypical antipsychotic medication (such as clozapine and olanzapine) with sulpiride, a substituted benzamide antipsychotic medication, may play a role in the management of treatment-resistant psychotic conditions. The objective of this study was to investigate any change in clinical symptomatology or side-effect profile in treatment-resistant schizophrenia patients receiving sulpiride in addition to olanzapine. Seventeen patients with treatment-resistant chronic schizophrenia, who were receiving olanzapine monotherapy for at least 6 months before study commencement, were randomized in a 1:1 fashion to receive either adjunctive treatment with sulpiride (study group) or to continue their pre-study treatment with olanzapine with no medication augmentation (control group), each for a period of 8 weeks. Changes in measures of positive and negative symptoms, anxiety, depression and extrapyramidal symptoms were assessed at baseline and at 8 weeks. Study observations indicated no significant differences in the changes in positive or negative symptomatology between patients receiving a combined regimen of olanzapine with sulpiride (600 mg/ day) augmentation and controls. However, a significantly greater improvement of depressive symptomatology (P Depression) was noted in the sulpiride augmentation group. These data indicate improvement in depressive symptomatology with sulpiride augmentation of olanzapine in treatment-resistant chronic schizophrenia patients.

  10. Long-acting muscarinic antagonists (LAMA) added to combination long-acting beta2-agonists and inhaled corticosteroids (LABA/ICS) versus LABA/ICS for adults with asthma.

    Science.gov (United States)

    Kew, Kayleigh M; Dahri, Karen

    2016-01-21

    Maintenance treatment with long-acting beta2-agonists and inhaled corticosteroids (LABA/ICS) can relieve asthma symptoms and reduce the frequency of exacerbations, but there are limited treatment options for people who do not gain control on combination LABA/ICS. Long-acting muscarinic antagonists (LAMA) are a class of inhaled drug which have been effective for people with chronic obstructive pulmonary disease and are now becoming available for people with asthma to take alongside their LABA/ICS inhaler. To assess the effects of adding a long-acting muscarinic antagonist (LAMA) to combination long-acting beta2-agonists (LABA) and inhaled corticosteroids (ICS) in adults whose asthma is not well controlled by LABA/ICS. We identified trials from the Cochrane Airways Review Group Specialised Register (CAGR) up to January 2016. We also searched ClinicalTrials.gov, the WHO trials portal, and reference lists of other reviews, and we contacted trial authors for additional information. We included parallel randomised controlled trials (RCTs) of at least 12 weeks' duration. Studies met the inclusion criteria if they compared LAMA as an add-on to LABA/ICS versus LABA/ICS alone for adults with asthma. We included studies reported as full text, those published as abstract only, and unpublished data. Primary outcomes were exacerbations requiring oral corticosteroids (OCS), validated measures of asthma control, and serious adverse events (including mortality). Two review authors screened searches and independently extracted details on risk of bias and numerical data. We analysed dichotomous data as odds ratios (ORs) and continuous data as mean differences (MD) using a random-effects model. We rated all outcomes using GRADE. We found four double-blind, double-dummy trials comparing LAMA to placebo, including 1197 people with asthma taking combination LABA/ICS. One of the trials was designed to study glycopyrronium bromide but was withdrawn prior to enrolment, and the other three

  11. Embryo transfer in no cycling Crioula and Quarter horse breeds treated with estradiol cipionate and long-acting progesterone

    Directory of Open Access Journals (Sweden)

    Fernanda Kaercher

    2011-12-01

    Full Text Available The aim of this work was to prepare the mares for embryo transfer. In group 1 (G1,treated, n=15, recipient mares in anoestrus or in a transition period were treated with 5.0, 3.0 and 2.0 mg of estradiol cipionate at the days 0, 1 and 2 respectively, beginning at the day of ovulation (DO. From the fourth day on, the mares this group received long-acting progesterone weekly, up to the 120 day of gestation. At D8, the embryo was collected from the donor and transferred to the recipient. At D12, the ultrasonographyc diagnosis of pregnancy was carried out. The control group (G2, not treated, n=20 was formed by cycling recipient mares, displaying ovulation at each 2 to 3 days after the donors mare ovulation. The pregnancy rate was higher (p<0.05 in the mares from G2 (85.0% than from G1 (53.3%. Thus, it could be concluded that the treated mares although showed lesser pregnancy rate than the cycling mare, were satisfactory alternative to be used mainly when there is no available cycling recipient.

  12. Insulin degludec, a long-acting once-daily basal analogue for type 1 and type 2 diabetes mellitus.

    Science.gov (United States)

    Berard, Lori; MacNeill, Gail

    2015-02-01

    Here, we discuss certain practical issues related to use of insulin degludec, a new long-acting basal insulin analogue. Degludec provides uniform ("peakless") action that extends over more than 24 hours and is highly consistent from dose to dose. Like the 2 previously available basal analogues (detemir and glargine), degludec is expected to simplify dose adjustment and enable patients to reach their glycemic targets with reduced risk of hypoglycemia. Phase 3 clinical trials involving type 1 and type 2 diabetes have demonstrated that degludec was noninferior to glargine in allowing patients to reach a target glycated hemoglobin (A1C) of 7%, and nocturnal hypoglycemia occurred significantly less frequently with degludec. In addition, when dosing intervals vary substantially from day to day, degludec continues to be effective and to maintain a low rate of nocturnal hypoglycemia. Degludec thus has the potential to reduce risk of nocturnal hypoglycemia, to enhance the flexibility of the dosing schedule and to improve patient and caregiver confidence in the stability of glycemic control. A dedicated injector, the FlexTouch prefilled pen, containing degludec 200 units/mL, will be recommended for most patients with type 2 diabetes. Degludec will also be available as 100 units/mL cartridges, to be used in the NovoPen 4 by patients requiring smaller basal insulin doses, including most patients with type 1 diabetes.

  13. Effects of the long-acting calcium channel blocker barnidipine hydrochloride on 24-h ambulatory blood pressure.

    Science.gov (United States)

    Kuwajima, Iwao; Abe, Keishi

    2002-02-01

    The effect of the long acting calcium channel blocker, barnidipine hydrochloride (barnidipine) on 24-h ambulatory blood pressure (ABP) was evaluated in J-MUBA (Japanese Multicentre Study on Barnidipine with Ambulatory Blood Pressure Monitoring). Following an observation period of two weeks, antihypertensive treatment with barnidipine was continued for at least six months. At the end of each period, ABP were measured. The patients were divided into high- and low-range groups based on ABP measurement. Throughout the 24 h, barnidipine exerted an excellent antihypertensive effect in the high-range group, but not in the low-range group. Barnidipine had comparable effects in the daytime and nighttime in inverted dippers and non-dippers, but it was more effective on daytime ABP than on nighttime ABP in dippers and in extreme dippers. Morning blood pressure before and after waking was evaluated before and after barnidipine administration in 233 patients. Barnidipine inhibited increases in blood pressure before and after waking, especially in surge-type patients whose blood pressure increased rapidly after waking. A positive correlation among 24-h ABP, daytime and night time ABP, morning blood pressure, and clinic blood pressure during the observation period and the antihypertensive effect of barnidipine was observed, with barnidipine exhibiting stronger antihypertensive effects in patients with persistently high blood pressure. It was concluded that the antihypertensive effects of barnidipine are maintained for 24 h but it has no excessive hypotensive effects on lower blood pressure and is thus a safe antihypertensive agent.

  14. Impulse Oscillometry; Therapeutic Impacts of Transdermal Long-Acting Beta-2 Agonist Patch in Elderly Asthma with Inhaled Corticosteroid Alone

    Directory of Open Access Journals (Sweden)

    Hiroshi Tanaka

    2012-01-01

    Full Text Available Growing interest had been focused on the involvement of the small airways in asthma, and impulse oscillometry (IOS has been utilized as pulmonary functions for detecting large and small airways diseases separately. IOS can measure respiratory resistance and reactance at multiple frequencies, not available by spirometry or body plethysmography, is non-invasive techniques and convenient for elderly patients with a low dependency on cooperation during tidal breathing. IOS indices were well correlated with not only predicted FEV1 but also FEF25-75, residual volume/total lung capacity, delta N2 of a single nitrogen washout test which representing air trapping and inhomogeneous ventilation in the distal lung. These parameters and QOL scores were improved by additional transdermal long-acting beta-2 agonist patch even in well-controlled elderly asthma treating with inhaled corticosteoids alone. IOS may have a complementary role of spirometry in detecting subtle airways changes in general practice. However, systemic studies are required to investigate the clinical implication of each IOS index.

  15. Development of long-acting bioadhesive vaginal gels of oxybutynin: formulation, in vitro and in vivo evaluations.

    Science.gov (United States)

    Tuğcu-Demiröz, Fatmanur; Acartürk, Füsun; Erdoğan, Deniz

    2013-11-30

    Overactive bladder (OAB) and vaginal dryness are common problems after menopause. Oxybutynin (OXY) is an antimuscarinic agent that has been available for more than 30 years in the treatment of OAB patients. The aim of the work reported in this paper was to develop long acting mucoadhesive gel formulations of OXY and to investigate their effects on blood levels compared to those of oral OXY immediate release tablets, in rabbits. Mucoadhesive gels were prepared with chitosan, hydroxypropyl methylcellulose (HPMC K100M) and Poloxamer 407 (Pluronic F 127). The physicopharmaceutical properties of gels were evaluated. The gel formulation which was prepared with HPMC K100M, exhibited the highest viscosity, the greatest adhesiveness, cohesiveness and mucoadhesion values. The formulation which was prepared from HPMC K100M showed suitable permeation characteristics across the vaginal mucosa. Comparative bioavailability studies were carried out on rabbits with vaginal HPMC gel, vaginal chitosan gel, vaginal OXY solution and commercially available oral Üropan tablets. It was concluded that the highest AUC and relative bioavailability values were obtained for the bioadhesive vaginal gel formulation prepared with HPMC K100M. Therefore, the mucoadhesive vaginal gels of OXY can be a promising and innovative alternative therapeutic system for the treatment of OAB. It can be safely used in cases of overactive bladder and as well as vaginal dryness after menopause.

  16. Long-acting Reversible Contraception Among Homeless Women Veterans With Chronic Health Conditions: A Retrospective Cohort Study.

    Science.gov (United States)

    Gawron, Lori M; Redd, Andrew; Suo, Ying; Pettey, Warren; Turok, David K; Gundlapalli, Adi V

    2017-09-01

    US women Veterans are at increased risk of homelessness and chronic health conditions associated with unintended pregnancy. Veterans Health Administration (VHA) provision of long-acting reversible contraception (LARC) can assist in healthy pregnancy planning. To evaluate perinatal risk factors and LARC exposure in ever-homeless women Veterans. A retrospective cohort study of women Veterans using VHA administrative data from fiscal years 2002-2015. We included 41,747 ever-homeless women Veterans age 18-44 years and 46,391 housed women Veterans matched by military service period. A subgroup of 7773 ever-homeless and 8674 matched housed women Veterans deployed in Iraq and Afghanistan [Operations Enduring Freedom/Iraqi Freedom/New Dawn (OEF/OIF/OND)] conflicts comprised a second analytic cohort. Descriptive statistics compared demographic, military, health conditions, and LARC exposure in ever-homeless versus housed women Veterans. Multivariable logistic regression explored factors associated with LARC exposure in the OEF/OIF/OND subgroup. All health conditions were significantly higher in ever-homeless versus housed Veterans: mental health disorder in 84.5% versus 48.7% (Phomeless women Veterans and providing LARC access. The prevalence of perinatal risk factors in ever-homeless women Veterans highlights a need for further programmatic enhancements to improve reproductive planning.

  17. Effects of Three Types of Long-acting Contraceptive Implants on Menstrual Blood Loss in 89 Women

    Institute of Scientific and Technical Information of China (English)

    韩丽晖; 范慧民; 龚泉; 谢争; 孟凡; 洪玉凤; 王文娟

    1999-01-01

    Objective: To study the effects of three types of contraceptive implants: the domestic No I , No I implants and Norplant on menstrual blood loss (MBL). Method: Eighty-nine healthy subjects were randomly allocated to three groups.Menstrual blood loss was measured before implanting and 3, 6, and 12 months after implantation. Results: MBL of the three groups prior to the use of implant were 43. 3±6. 9ml,48.9±4. 3 ml, and 43.7±5. 5ml respectively, and decreased significantly at all post-implantation periods. MBLs were 32. 8±13. 2ml, 24. 8±5. 5ml, and 19. 7±9.3ml at the 3rd month after implantation and 23. 9±5. 9 ml, 40. 8±10. 4 ml, 25. 9±6. 0 ml at the 12th month after implantation respectively, sigmficantly less than before implantation(P<0. 05~0. 01). A tendency was seen in increase of hemoglobin concentraition. Conclusion: Long-acting contraceptive implants decreased menstrual blood loss and elevates hemoglobin concentration. They are applicable to women as a contraceptive method without blood loss effects.

  18. Study of long-acting reversible contraceptive use in a UK primary care database: validation of methodology.

    Science.gov (United States)

    Cea Soriano, Lucía; Wallander, Mari-Ann; Andersson, Susan W; Requena, Gema; García-Rodríguez, Luis A

    2014-02-01

    OBJECTIVES To develop and validate algorithms to identify new users of long-acting reversible contraceptives (LARCs) in a primary care database, The Health Improvement Network (THIN). METHODS Women in THIN aged 12 to 49 years in 2005 were studied. THIN was searched using Read and MULTILEX codes to identify new users of copper intrauterine devices (Cu-IUDs), the levonorgestrel-releasing intrauterine system (LNG-IUS) and progestogen-only implants. Validation was undertaken for a randomly selected sample of 398 LARC users, in which their primary care physicians were asked to complete a questionnaire detailing LARC use. RESULTS Questionnaires were received for 379 patients (95%), confirming 316 (83%) as new LARC users. Confirmation rates for Cu-IUDs, the LNG-IUS and progestogen-only implants were 64%, 94% and 89%, respectively. The use of Read codes alone had the lowest confirmation rate, particularly for Cu-IUD users. Confirmation rates increased by using MULTILEX codes when available, or by examination of computerised medical records. CONCLUSIONS Computer algorithms were used to identify new LARC users. While THIN is a useful resource for studying LARC uptake, steps to gather additional information are necessary to ensure the validity of LARC classification.

  19. Factors impacting knowledge and use of long acting and permanent contraceptive methods by postpartum HIV positive and negative women in Cape Town, South Africa: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Credé Sarah

    2012-03-01

    Full Text Available Abstract Background The prevention of unintended pregnancies among HIV positive women is a neglected strategy in the fight against HIV/AIDS. Women who want to avoid unintended pregnancies can do this by using a modern contraceptive method. Contraceptive choice, in particular the use of long acting and permanent methods (LAPMs, is poorly understood among HIV-positive women. This study aimed to compare factors that influence women's choice in contraception and women's knowledge and attitudes towards the IUD and female sterilization by HIV-status in a high HIV prevalence setting, Cape Town, South Africa. Methods A quantitative cross-sectional survey was conducted using an interviewer-administered questionnaire amongst 265 HIV positive and 273 HIV-negative postpartum women in Cape Town. Contraceptive use, reproductive history and the future fertility intentions of postpartum women were compared using chi-squared tests, Wilcoxon rank-sum and Fisher's exact tests where appropriate. Women's knowledge and attitudes towards long acting and permanent methods as well as factors that influence women's choice in contraception were examined. Results The majority of women reported that their most recent pregnancy was unplanned (61.6% HIV positive and 63.2% HIV negative. Current use of contraception was high with no difference by HIV status (89.8% HIV positive and 89% HIV negative. Most women were using short acting methods, primarily the 3-monthly injectable (Depo Provera. Method convenience and health care provider recommendations were found to most commonly influence method choice. A small percentage of women (6.44% were using long acting and permanent methods, all of whom were using sterilization; however, it was found that poor knowledge regarding LAPMs is likely to be contributing to the poor uptake of these methods. Conclusions Improving contraceptive counselling to include LAPM and strengthening services for these methods are warranted in this setting

  20. Efficacy of amisulpride and olanzapine for negative symptoms and cognitive impairments: An open-label clinical study

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    Subodh Kumar

    2014-01-01

    Full Text Available Background: Negative symptoms and diminished cognitive ability are also considered as core features of schizophrenia. There are many studies in which negative symptoms and cognitive impairments are individually treated with atypical antipsychotic in comparison with either a placebo or a typical antipsychotic. There is paucity of studies comparing the efficacy of olanzapine and amisulpride on improvement of negative symptoms and cognitive impairments. Aim: To examine the effectiveness of amisulpride and olanzapine in treatment of negative symptoms and cognitive impairments in schizophrenia. Materials and Methods: Total 40 adult inpatients diagnosed as schizophrenia fulfilling inclusion/exclusion criteria were included in the study with their informed consent. These patients were recruited consecutively to one of the two drug regimen group, i.e. tab Amisulpride (100-300 mg/day and tab Olanzapine (10-20 mg. Patients were evaluated on day 0 and day 60 with various rating scales like Scale for the Assessment of Negative Symptoms (SANS, Scale for the Assessment of Positive Symptoms (SAPS, Schizophrenia Cognition Rating Scale (SCoRS, Brief Psychiatric Rating Scale (BPRS, Calgary Depression Scale for Schizophrenia (CDSS, and three different scales to measure drug side effects. Results: The mean SANS score in amisulpride and olanzapine group at day 0 and day 60 were 83.89 (±12.67 and 21.00 (±11.82 and 84.40 (±13.22 and 26.75 (±12.41, respectively. The mean rank of SCoRS global in amisulpride and olanzapine group at day 0 and day 60 were 4.78 (±1.13 and 2.78 (±0.63 and 4.85 (±1.18 and 3.30 (±1.12, respectively. The percentage improvement in SANS, SAPS, SCoRS interviewer, and SCoRS global in amisulpride group are 74.96%, 13.36%, 54.14%, and 42.00%, respectively. Similarly in olanzapine group percentage improvement in SANS, SAPS, SCoRS interviewer, and SCoRS global are 68.30%, 30.28%, 35.22%, and 31.95%, respectively. There is significant

  1. RESEARCH ON THE STABILITY OF LONG-ACTING INJECTION OF KETOPROFEN%酮洛芬长效注射剂的稳定性研究

    Institute of Scientific and Technical Information of China (English)

    万昕; 尹宗宁; 程强

    2004-01-01

    目的:考察酮洛芬长效注射剂的稳定性.方法:建立酮洛芬长效注射剂的含量测定方法,进行加速试验及室温留样试验,考察其外观、pH值、含量变化.结果:本品对光稳定,对热稳定性较差.结论:本品应置阴凉处保存.

  2. Pregnancy exposure to olanzapine, quetiapine, risperidone, aripiprazole and risk of congenital malformations. A systematic review

    DEFF Research Database (Denmark)

    Ennis, Zandra Nymand; Damkier, Per

    2015-01-01

    To review available data on first-trimester exposure to olanzapine, quetiapine, risperidone and aripiprazole and risk of congenital malformations. We performed a systematic literature search in accordance with PRISMA guidelines identifying studies containing original data on first......-trimester exposure and pregnancy outcome with respect to congenital malformations. Cumulated data for olanzapine were 1090 first-trimester-exposed pregnancies with 38 malformations resulting in a malformation rate of 3.5%. The corresponding numbers for quetiapine, risperidone and aripiprazole were 443/16 (3.6%), 432...... of congenital malformation. Data for quetiapine and risperidone do not suggest a substantially increased risk, while the risk estimate for aripiprazole remains imprecise owing to a low amount of data....

  3. A patient with schizophrenia presenting with post-lobotomy catatonia treated with olanzapine: a case report.

    Science.gov (United States)

    Kumagai, Ryo; Kitazawa, Maiko; Ishibiki, Yoshiro; Narumi, Kenji; Ichimiya, Yosuke

    2017-05-01

    A 79-year-old Japanese woman with schizophrenia was hospitalized because of idiopathic duodenal stenosis. Three days after discontinuing ingestion, including the administration of psychotropic drugs, the patient demonstrated incoherent behaviour and strong general muscle tension, and was unable to engage in conversation. Computed tomography indicated bilateral regions of low density in the frontal lobes, subsequent to which she was diagnosed with post-lobotomy catatonia. Administration of olanzapine (10 mg/day) improved the patient's condition within a short period. Previous studies have demonstrated an association between the dysfunction of frontal circuits and catatonia; therefore, the observed catatonic episode might relate to the disconnection of nerve fibres in the prefrontal lobes induced by her lobotomy. Olanzapine was likely effective in treating catatonia because of its reported efficacy in improving frontal lobe function. © 2016 The Authors. Psychogeriatrics © 2016 Japanese Psychogeriatric Society.

  4. Fever development in neuroleptic malignant syndrome during treatment with olanzapine and clozapine.

    Science.gov (United States)

    Szota, Anna; Ogłodek, Ewa; Araszkiewicz, Aleksander

    2013-01-01

    Neuroleptic malignant syndrome (NMS) is the most dangerous life-threatening complication of antipsychotic medication. It's development is connected with the blockade of dopaminergic transmission (D2 receptors) in the nigrostriatal system of the brain. Fever is one of the main symptoms of this syndrome and it's elevation is due to the activation of the immune system. Numerous studies report that treatment with clozapine (doses 37.5-600 mg) or olanzapine (doses 10-25 mg) or the use of these drugs in polytherapy cause pyrexia between 37.8-40.6 °C. Additionally, levels of proinflammatory interleukins such as IL-6, IL-1,TNF-α were increased. The aim of this article is to describe how olanzapine and clozapine influence fever development in NMS, in relation to the dose of the drug taken by schizophrenic patients including changes in immunological system.

  5. Acute-Onset Type 1 Diabetes that Developed During the Administration of Olanzapine

    Science.gov (United States)

    Iwaku, Kenji; Otuka, Fumiko; Taniyama, Matsuo

    2017-01-01

    The patient was 32-year-old man, who received olanzapine for schizophrenia and developed polyuria and thirst without drinking soft-drinks after 4 months. Five months after the initiation of treatment, he developed diabetic ketoacidosis (blood glucose: 490 mg/dL, HbA1c: 15.5%). He was diagnosed with type 1 diabetes (glutamic acid decarboxylase (GAD)-Ab: 5.6 U/mL, IA-2 Ab: 5.9 U/mL, fasting C-peptide: 0.12 ng/mL) and was put on intensive insulin therapy. At four months after the onset of 1A diabetes, he experienced a honeymoon phase that was sustained until the 40th month of treatment. We hypothesize that the administration of olanzapine to a patient with pre-type 1A diabetes induced marked hyperglycemia and accelerated the onset of type 1A diabetes. PMID:28154279

  6. [Preparation and the biological effect of fusion protein GLP-1-exendin-4/ IgG4(Fc) fusion protein as long acting GLP-1 receptor agonist].

    Science.gov (United States)

    Zheng, Yun-cheng

    2015-12-01

    . It can be used as a long-acting GLP-1 agonists.

  7. Factors influencing use of long-acting versus short-acting contraceptive methods among reproductive-age women in a resource-limited setting.

    Science.gov (United States)

    Tibaijuka, Leevan; Odongo, Robert; Welikhe, Emma; Mukisa, Wilber; Kugonza, Lilian; Busingye, Imelda; Nabukalu, Phelomena; Ngonzi, Joseph; Asiimwe, Stephen B; Bajunirwe, Francis

    2017-04-04

    Unplanned pregnancy remains a common problem in many resource-limited settings, mostly due to limited access to modern family planning (FP) services. In particular, use of the more effective long-acting reversible contraceptive (LARC) methods (i.e., intrauterine devices and hormonal implants) remains low compared to the short-acting methods (i.e., condoms, hormonal pills, injectable hormones, and spermicides). Among reproductive-age women attending FP and antenatal care clinics in Uganda, we assessed perceptions and practices regarding the use of modern contraceptive methods. We specifically aimed to evaluate factors influencing method selection. We performed a mixed-methods cross-sectional study, in which we administered structured interviews to 180 clients, and conducted 4 focus group discussions (FGDs) with 36 clients and 8 in-depth personal qualitative interviews with health service providers. We summarized quantitative data and performed latent content analysis on transcripts from the FGDs and qualitative interviews. The prevalence of ever use for LARC methods was 23%. Method characteristics (e.g., client control) appeared to drive method selection more often than structural factors (such as method availability) or individual client characteristics (such as knowledge and perceptions). The most common reasons for choosing LARC methods were: longer protection; better child-spacing; and effectiveness. The most common reasons for not choosing LARC methods included requiring a client-controlled method and desiring to conceive in the near future. The most common reasons for choosing short-acting methods were ease of access; lower cost; privacy; perceived fewer side effects; and freedom to stop using a method without involving the health provider. The personal characteristics of clients, which appeared to be important were client knowledge and number of children. The structural factor which appeared to be important was method availability. Our results suggest that

  8. 长效奥曲肽治疗垂体促甲状腺激素瘤一例临床探讨%A case of thyrotropin-secreting pituitary adenoma treated with long-acting octreotide formulation

    Institute of Scientific and Technical Information of China (English)

    陈晓平; 王昕; 邢小燕; 卢毅; 李光伟

    2011-01-01

    A 56-year-old man with 1-year history of palpitation, heat intolerance and sweating, was diagnosed as thyrotropin (TSH) -secreting pituitary adenoma based on the symptoms of hypermetabolism, enlarged thyroid gland, inappropriately increased serum TSH concomitantly elevated plasma thyroid hormones and a pituitary tumor demonstrated on magnetic resonance imaging. Long-acting octreotide formulation was administered at a dose of 20 mg intramuscularly. Tumor volume shrinkage and improvement of thyroid function was achieved after a single drug injection; and the thyroid function returned to normal in 28 days. It is suggested that long-acting octreotide formulation might be used as a routine therapeutic approach prior to pituitary surgery, which may enhance the effectiveness of surgery and postoperative recovery.%一例56岁男性垂体促甲状腺激素(TSH)瘤患者,病史一年,有心悸、怕热、多汗等高代谢症候群;甲状腺肿大;在血甲状腺激素水平明显增加的同时,TSH水平升高;核磁扫描示垂体肿瘤.经长效奥曲肽20mg注射一次治疗后,肿瘤体积缩小,甲状腺功能明显好转,治疗后第28天转为正常.长效奥曲肽可为TSH瘤患者手术前的常规用药,有利于手术顺利进行及术后康复.

  9. Physiogenomic comparison of weight profiles of olanzapine- and risperidone-treated patients.

    Science.gov (United States)

    Ruaño, G; Goethe, J W; Caley, C; Woolley, S; Holford, T R; Kocherla, M; Windemuth, A; de Leon, J

    2007-05-01

    Atypical antipsychotics induce pre-diabetic symptoms in some but not all patients, characterized most notably by elevated weight. The side effect profiles of the various drugs in the class differ, however, raising the possibility of drug-specific mechanisms for similar side effects. We used physiogenomic analysis, an approach previously employed to study the genetics of drug and diet response, to discover and compare genetic associations with weight profiles observed in patients treated with olanzapine and risperidone as an approach to unraveling contrasting mechanistic features of both drugs. A total of 29 single nucleotide polymorphisms (SNPs) were selected from 13 candidate genes relevant to two potential pharmacological axes of psychotropic-related weight profiles, appetite peptides and peripheral lipid homeostasis. We applied physiogenomic analysis to a cross-section of 67 and 101 patients being treated with olanzapine and risperidone, respectively, and assessed genetic associations with the weight profiles. Weight profiles in patients treated with olanzapine were significantly associated with SNPs in the genes for apolipoprotein E, apolipoprotein A4 and scavenger receptor class B, member 1. Weight profiles in patients treated with risperidone were significantly associated with SNPs in the genes for leptin receptor, neuropeptide Y receptor Y5 and paraoxonase 1. These results are consistent with contrasting mechanisms for the weight profile of patients treated with these drugs. Genes associated with olanzapine weight profiles may be related to peripheral lipid homeostatic axes, whereas those associated with risperidone's may be related to brain appetite peptide regulation. Future physiogenomic studies will include neurotransmitter receptor SNPs and validation in independent samples.

  10. Schizophrenia relapse after stopping olanzapine treatment during pregnancy: a case report

    Directory of Open Access Journals (Sweden)

    Ifteni P

    2014-10-01

    Full Text Available Petru Ifteni,1,2 Marius A Moga,1 Victoria Burtea,1,2 Christoph U Correll3,4 1Faculty of Medicine, Transilvania University, Brasov, Romania; 2Psychiatry and Neurology Hospital, Brasov, Romania; 3Department of Psychiatry, The Zucker Hillside Hospital, North Shore-Long Island Jewish (LIJ Health System, New York, NY, USA; 4Hofstra North Shore-LIJ School of Medicine, New York, NY, USA Abstract: Women with schizophrenia have a high risk for symptom exacerbation or relapse during pregnancy and thereafter. Relapses are more frequent when antipsychotics are discontinued. This paper describes the case of a 28-year old woman with schizophrenia who continued treatment with olanzapine during the first trimester. Olanzapine, a second-generation antipsychotic, was administered at a therapeutic dose from week 1 of gestation until week 13 when she reported the pregnancy to her psychiatrist. Despite the psychiatrist’s recommendation to continue treatment, the patient stopped olanzapine at 20 weeks. She was hospitalized at week 36 for a schizophrenia relapse and was transferred to the obstetrics department where she gave birth by Cesarean section to a normal child. This case is important, illustrating the perils of unplanned pregnancy during antipsychotic treatment and abrupt discontinuation. Ultimately, clinical decisions should be made on a case-by-case basis, weighing the risks to the mother in terms of symptom exacerbation and relapse if antipsychotic treatment is discontinued, and the potential risk to the fetus regarding possible teratogenic effects of continued antipsychotic treatment. Keywords: relapse, pregnancy, schizophrenia, olanzapine

  11. Report of a Rare Case of Olanzapine and Risperidone Induced Hypomania

    Directory of Open Access Journals (Sweden)

    AR Zahiroddin

    2006-07-01

    Full Text Available Introduction & Objective: Hypomania is a mood disorder with symptoms of constantly high expansive or irritable mood. After a 4-day period, the patient feels to be in need of less sleep, being talkative, or feeling pressure if not treated kindly, having flight of ideas, distractibility, and increase in goal oriented activities (including social, occupational, educational or sexual activities and being extravagant. Hypomania could be a mood episode of bipolar I and II mood disorder or cyclothymia and could be resulted from consumption of drugs, materials, Electro Convulsive Therapy (ECT or photo therapy. Case: The present report is the case of a 57-year old married woman, who has had a record of bipolar I mood disorder since 30 years ago. The patient was hospitalized once in psychiatry hospital and referred to psychiatry office 2 years ago. She has been under medication therapy by lithium 600 mg, nortriptyline 75 mg, and colonazpam 1 mg. She has taken risperidone 2 mg, the symptoms of hypomania have revealed. After stopping the consumption of risperidone, the treatment continued by lithium tablet 900 mg, eskazina tablet 4 mg, nortriptyline 75 mg for one day. She was under care for 15 months and then due to muscle complications of lithium, pessimism, auditory and visual hallucination, she was recommended to take olanzapine tablet 5 mg once every night. Two days after taking olanzapine the symptoms of hypomania revealed. Consumption of olanzapine was then stopped and the symptoms disappeared and she was brought under control after taking sodiumvalproate tablet. Conclusion: Rarely could Hypomania be a mood episode induced by consuming atypical antipsychotics such as risperidone and olanzapine.

  12. Direct association between orbitofrontal atrophy and the response of psychotic symptoms to olanzapine in schizophrenia.

    Science.gov (United States)

    Molina, Vicente; Sanz, Javier; Benito, Carlos; Palomo, Tomás

    2004-07-01

    The study of cerebral variables associated with response to neuroleptics holds interest from both theoretical and clinical points of view. To date, no studies have aimed to identify predictors of response to olanzapine based on cerebral measurements. Here, we used magnetic resonance to assess the relationship between volumes of the prefrontal (dorsolateral and orbitofrontal) and temporal (temporal lobe and hippocampus) cortical regions and ventricles and, on the other hand, the response to olanzapine in 16 schizophrenic patients. Data from 42 healthy controls were used to calculate volume residuals in the patients, defined as deviations from the expected values, given individual age and intracranial volume. Residuals thus represent the effect of illness on regional measurements. The association between clinical change and those residuals was calculated separately for the positive, negative and total scores from the Positive and Negative Syndrome Scale (PANSS). There was a significant direct association between the degree of orbitofrontal atrophy and the improvement of positive symptoms with olanzapine. No predictors were found for change in the negative dimension. A trend was found for patients with larger ventricles to show a greater global decrease in total PANSS scores. Neither age nor duration of illness explained a significant proportion of the symptom improvement. This result, together with others from the literature, supports the idea that atypical antipsychotics may offer some benefit to patients with significant regional atrophy, and this may have implications for the choice of antipsychotic in clinical practice.

  13. Spectroscopic and molecular docking studies on the interaction of the drug olanzapine with calf thymus DNA

    Science.gov (United States)

    Shahabadi, Nahid; Bagheri, Somayeh

    2015-02-01

    The present study investigated the binding interaction between olanzapine and calf thymus DNA (ct-DNA) using emission, absorption, circular dichroism, viscosity measurements and molecular modeling. Thermodynamic parameters (ΔH < 0 and ΔS < 0) indicated that hydrogen bond and van der Waals play main roles in the binding of the drug to ct-DNA. Spectrophotometric studies of the interaction of olanzapine with DNA have shown that it could bind to ct-DNA (Kb = 2 × 103 M-1). The binding constant is comparable to standard groove binding drugs. Competitive fluorimetric studies with Hoechst 33258 have shown that olanzapine exhibits the ability to displace the DNA-bound Hoechst 33258 indicating that binds strongly in minor groove of DNA helix. Furthermore, the drug induces detectable changes in the CD spectrum of ct-DNA as well as changes in its viscosity. All of the experimental results prove that the groove binding must be predominant. The results obtained from experimental data were in good agreement with molecular modeling studies.

  14. Olanzapine-Induced Diabetic Ketoacidosis and Neuroleptic Malignant Syndrome with Rhabdomyolysis: A Case Report

    Directory of Open Access Journals (Sweden)

    Young Kyoung Sa

    2013-03-01

    Full Text Available Atypical antipsychotics have replaced conventional antipsychotics in the treatment of schizophrenia because they have less of a propensity to cause undesirable neurologic adverse events including extrapyramidal symptoms, tardive dyskinesia, and neuroleptic malignant syndrome (NMS. However, atypical antipsychotics have been known to result in various metabolic complications such as impaired glucose tolerance, diabetes and even diabetic ketoacidosis (DKA. In addition, a number of NMS cases have been reported in patients treated with atypical antipsychotics, although the absolute incidence of neurologic side effects is currently significantly low. Here, we report a patient who simultaneously developed DKA, acute renal failure and NMS with rhabdomyolysis after olanzapine treatment. Olanzapine-induced metabolic complications and NMS were dramatically improved with cessation of the olanzapine treatment and initiation of supportive management including fluid therapy, hemodialysis, and intensive glycemic control using insulin. At short-term follow-up, insulin secretion was markedly recovered as evidenced by a restoration of serum C-peptide level, and the patient no longer required any hypoglycemic medications. Despite the dramatic increase in the use of atypical antipsychotics treatment, individualized treatments along with careful monitoring may be prudent for high risk or vulnerable patients in order to avoid the development of metabolic side effects.

  15. Plasma metabonomics study of first-Episode schizophrenia treated with olanzapine in female patients.

    Science.gov (United States)

    Qiao, Ying; Zhang, Lei; He, Shen; Wen, Hui; Yu, Yi-Min; Cao, Chun-Hua; Li, Hua-Fang

    2016-03-23

    Schizophrenia is a persistent chronic mental illness with an unknown pathogenic mechanism; no empirical laboratory-based tests are available to support the diagnosis of schizophrenia or to identify biomarkers correlated with the therapeutic effect of olanzapine. For this study, 15 female first-episode, drug-naïve patients with schizophrenia and 15 healthy female volunteers were recruited. Tests for blood glucose and lipids were conducted at baseline and after 4 weeks of treatment with olanzapine. UPLC-MS based metabonomic analysis was performed on both case and control groups to identify biomarkers of schizophrenia at baseline and to explore which biomarkers correlated with the therapeutic effect of olanzapine after a 4-week treatment. Compared with the control group, the case group showed significant changes in plasma metabolites. Thirteen distinct metabolites were identified. Among all the therapeutically effective cases, levels of these metabolites appeared to shift towards the normal trend; 8 of the identified 13 metabolites changed dramatically. The metabolites that we found are potential biomarkers for the diagnosis and treatment of schizophrenia.

  16. Addition of inhaled long-acting beta2-agonists to inhaled steroids as first line therapy for persistent asthma in steroid-naive adults and children.

    LENUS (Irish Health Repository)

    Ni Chroinin, Muireann

    2009-01-01

    Consensus statements recommend the addition of long-acting inhaled ss2-agonists (LABA) only in asthmatic patients who are inadequately controlled on inhaled corticosteroids (ICS). It is not uncommon for some patients to be commenced on ICS and LABA together as initial therapy.

  17. HelpDesk answers: is it safe to add long-acting β-2 agonists to inhaled corticosteroids in patients with persistent asthma?

    Science.gov (United States)

    Townsend, Laurie; Madlon-Kay, Diane J

    2015-06-01

    Possibly. Long-acting β-2 agonists (LABAs) used in combination with inhaled corticosteroids (ICS) don't appear to increase all-cause mortality or serious adverse events in patients with persistent asthma compared with ICS alone. Studies showing an increase in catastrophic events had serious methodologic issues. A large surveillance study is ongoing.

  18. Impact of multiple-dose versus single-dose inhaler devices on COPD patients' persistence with long-acting beta2-agonists: a dispensing database analysis

    NARCIS (Netherlands)

    Boven, J.F. van; Raaij, J.J. van; Galien, R. van der; Postma, M.J.; Molen, T. van der; Dekhuijzen, P.N.R.; Vegter, S.

    2014-01-01

    BACKGROUND: With a growing availability of different devices and types of medication, additional evidence is required to assist clinicians in prescribing the optimal medication in relation to chronic obstructive pulmonary disease (COPD) patients' persistence with long-acting beta2-agonists (LABAs).

  19. Impact of multiple-dose versus single-dose inhaler devices on COPD patients' persistence with long-acting beta(2)-agonists : a dispensing database analysis

    NARCIS (Netherlands)

    van Boven, Job F. M.; van Raaij, Joost J.; van der Galiën, Ruben; Postma, Maarten J.; van der Molen, Thys; Dekhuijzen, P. N. Richard; Vegter, Stefan

    2014-01-01

    BACKGROUND: With a growing availability of different devices and types of medication, additional evidence is required to assist clinicians in prescribing the optimal medication in relation to chronic obstructive pulmonary disease (COPD) patients' persistence with long-acting beta(2)-agonists

  20. A double-blind comparison of the effect of the antipsychotics haloperidol and olanzapine on sleep in mania

    Directory of Open Access Journals (Sweden)

    R.A. Moreno

    2007-03-01

    Full Text Available The effects of haloperidol and olanzapine on polysomnographic measures made in bipolar patients during manic episodes were compared. Twelve DSM-IV mania patients were randomly assigned to receive either haloperidol (mean ± SD final dosage: 5.8 ± 3.8 mg or olanzapine (mean ± SD final dosage: 13.6 ± 6.9 mg in a 6-week, double-blind, randomized, controlled clinical trial. One-night polysomnographic evaluation was performed before and after the haloperidol or olanzapine treatment. Psychopathology and illness severity were rated respectively with the Young Mania Rating Scale (YMRS and the Clinical Global Impressions - Bipolar version (CGI-BP. There was a significant improvement in the YMRS and CGI-BP scores at the end of the study for both groups. Mixed ANOVA used to compare the polysomnographic measures of both drugs demonstrated significant improvement in sleep measures with olanzapine. In the olanzapine group, statistically significant time-drug interaction effects on sleep continuity measures were observed: sleep efficiency (mean ± SEM pre-treatment value: 6.7 ± 20.3%; after-treatment: 85.7 ± 10.9%, total wake time (pre-treatment: 140.0 ± 92.5 min; after-treatment: 55.2 ± 44.2 min, and wake time after sleep onset (pre-treatment: 109.7 ± 70.8 min; after-treatment: 32.2 ± 20.7 min. Conversely, improvement of polysomnographic measures was not observed for the haloperidol group (P > 0.05. These results suggest that olanzapine is more effective than haloperidol in terms of sleep-promoting effects, although olanzapine is comparatively as effective as haloperidol in treating mania. Polysomnography records should provide useful information on how manic states can be affected by psychopharmacological agents.

  1. Medroxyprogesterone Injection

    Science.gov (United States)

    Medroxyprogesterone intramuscular (into a muscle) injection and medroxyprogesterone subcutaneous (under the skin) injection are used to prevent pregnancy. Medroxyprogesterone subcutaneous injection is also used to treat endometriosis (a condition in which ...

  2. Pentamidine Injection

    Science.gov (United States)

    Pentamidine injection is used to treat pneumonia caused by a fungus called Pneumocystis carinii. It is in ... Pentamidine injection comes as powder to be mixed with liquid to be injected intramuscularly (into a muscle) ...

  3. Urban-rural differences in attitudes and practices toward long-acting reversible contraceptives among family planning providers in Texas.

    Science.gov (United States)

    Vaaler, Margaret L; Kalanges, Lauri K; Fonseca, Vincent P; Castrucci, Brian C

    2012-03-01

    Despite the elevated rates of teen and unplanned pregnancies across the United States, long-acting reversible contraceptives (LARCs) remain a less utilized birth control method. The present study investigated family planning providers' attitudes and considerations when recommending family planning methods and LARCs to clients. Additionally, this study explored whether urban-rural differences exist in providers' attitudes toward LARCs and in clients' use of LARCs. Data were collected using an online survey of family planning providers at Title X clinics in Texas. Survey data was linked to family planning client data from the Family Planning Annual Report (2008). Findings indicated that, although providers were aware of the advantages of LARCs, clients' LARC use remains infrequent. Providers reported that the benefits of hormone implants include their effectiveness for 3 years and that they are an option for women who cannot take estrogen-based birth control. Providers acknowledged the benefits of several types of LARCs; however, urban providers were more likely to acknowledge the benefits of hormone implants compared with their rural counterparts. Results also indicated barriers to recommending LARCs, such as providers' misinformation about LARCs and their caution in recommending LARCs to adolescents. However, findings also indicated providers lack training in LARC insertion, specifically among those practicing in rural areas. In light of the effectiveness and longevity of LARCs, teenagers and clients living in rural areas are ideal LARC candidates. Increased training among family planning providers, especially for those practicing in rural areas, may increase their recommendations of LARCs to clients. Copyright © 2012 Jacobs Institute of Women

  4. A phase 2 trial of long-acting TransCon growth hormone in adult GH deficiency

    Directory of Open Access Journals (Sweden)

    Charlotte Höybye

    2017-03-01

    Full Text Available TransCon growth hormone is a sustained-release human growth hormone prodrug under development in which unmodified growth hormone is transiently linked to a carrier molecule. It is intended as an alternative to daily growth hormone in the treatment of growth hormone deficiency. This was a multi-center, randomized, open-label, active-controlled trial designed to compare the safety (including tolerability and immunogenicity, pharmacokinetics and pharmacodynamics of three doses of weekly TransCon GH to daily growth hormone (Omnitrope. Thirty-seven adult males and females diagnosed with adult growth hormone deficiency and stable on growth hormone replacement therapy for at least 3 months were, following a wash-out period, randomized (regardless of their pre-study dose to one of three TransCon GH doses (0.02, 0.04 and 0.08 mg GH/kg/week or Omnitrope 0.04 mg GH/kg/week (divided into 7 equal daily doses for 4 weeks. Main outcomes evaluated were adverse events, immunogenicity and growth hormone and insulin-like growth factor 1 levels. TransCon GH was well tolerated; fatigue and headache were the most frequent drug-related adverse events and reported in all groups. No lipoatrophy or nodule formation was reported. No anti-growth hormone-binding antibodies were detected. TransCon GH demonstrated a linear, dose-dependent increase in growth hormone exposure without accumulation. Growth hormone maximum serum concentration and insulin-like growth factor 1 exposure were similar after TransCon GH or Omnitrope administered at comparable doses. The results suggest that long-acting TransCon GH has a profile similar to daily growth hormone but with a more convenient dosing regimen. These findings support further TransCon GH development.

  5. Validation of the manufacturing process used to produce long-acting recombinant factor IX Fc fusion protein.

    Science.gov (United States)

    McCue, J; Osborne, D; Dumont, J; Peters, R; Mei, B; Pierce, G F; Kobayashi, K; Euwart, D

    2014-07-01

    Recombinant factor IX Fc (rFIXFc) fusion protein is the first of a new class of bioengineered long-acting factors approved for the treatment and prevention of bleeding episodes in haemophilia B. The aim of this work was to describe the manufacturing process for rFIXFc, to assess product quality and to evaluate the capacity of the process to remove impurities and viruses. This manufacturing process utilized a transferable and scalable platform approach established for therapeutic antibody manufacturing and adapted for production of the rFIXFc molecule. rFIXFc was produced using a process free of human- and animal-derived raw materials and a host cell line derived from human embryonic kidney (HEK) 293H cells. The process employed multi-step purification and viral clearance processing, including use of a protein A affinity capture chromatography step, which binds to the Fc portion of the rFIXFc molecule with high affinity and specificity, and a 15 nm pore size virus removal nanofilter. Process validation studies were performed to evaluate identity, purity, activity and safety. The manufacturing process produced rFIXFc with consistent product quality and high purity. Impurity clearance validation studies demonstrated robust and reproducible removal of process-related impurities and adventitious viruses. The rFIXFc manufacturing process produces a highly pure product, free of non-human glycan structures. Validation studies demonstrate that this product is produced with consistent quality and purity. In addition, the scalability and transferability of this process are key attributes to ensure consistent and continuous supply of rFIXFc.

  6. The Impact of Balanced Counseling on Contraceptive Method Choice and Determinants of Long Acting and Reversible Contraceptive Continuation in Nepal.

    Science.gov (United States)

    Sapkota, Sabitri; Rajbhandary, Ruchita; Lohani, Shilpa

    2016-03-08

    Introduction Long-acting reversible contraceptives (LARCs) reduce rates of unintended pregnancies and repeat abortion. Uptake and continuation rates of LARCs are very low in Nepal, despite free provision from most health facilities. We sought to establish the effectiveness of a new approach to LARC promotion in Nepal. Methods We examined change in contraceptive method mix in Nepal using service data resulting from introduction of a balanced counseling (BC) approach to family planning (FP). All staff located at nine randomly selected FP sites were trained and began applying BC in April and May 2014. Women who accepted LARCs from a participating facility were re-contacted at 1, 3, 6 and 12 months. We estimated the LARC continuation rate and assessed determinants of continuation using descriptive analysis, Kaplan-Meier survival curves and univariate and multivariate Cox proportional hazard analysis. Results A total of 5744 women received BC between April and July 2014. 1580 women (27.5 %) took up LARCs, raising its contribution to contraceptive method mix at [organization] to 40 %, significantly higher than the 15 % recorded in 2013. 913 women were followed-up, and the LARC continuation rate at 12 months was 82 %. Women's reported satisfaction with LARC [AHR 0.23; 95 % CI 0.14-0.39, p = 0.000] was the single strongest determinant of LARC continuation after adjusting for all background characteristics. Discussion The findings suggest BC is an effective approach for increasing LARC uptake in Nepal. The rate of LARC continuation and its determinants are important inputs to strategies for improved delivery of FP services.

  7. Long acting octreotide in the treatment of advanced hepatocellular cancer and overexpression of somatostatin receptors: Randomized placebo-controlled trial

    Institute of Scientific and Technical Information of China (English)

    D Dimitroulopoulos; D Daskalopoulou; E Paraskevas; D Xinopoulos; K Tsamakidis; A Zisimopoulos; E Andriotis; D Panagiotakos; A Fotopoulou; C Chrysohoou; A Bazinis

    2007-01-01

    AIM: To estimate if and to what extent long acting octreotide (LAR) improves survival and quality of life in patients with advanced hepatocellular carcinoma (HCC).METHODS: A total of 127 cirrhotics, stages A-B, due to chronic viral infections and with advanced HCC, were enrolled in the study. Scintigraphy with 111Indium labeled octreotide was performed in all cases. The patients with increased accumulation of radionuclear compound were randomized to receive either oral placebo only or octreotide/octreotide LAR only as follows: octreotide 0.5mg s.c. Every 8 h for 6 wk, at the end of wk 4-8 octreotide LAR 20 mg I.m. And at the end of wk 12 and every 4 wk octreotide LAR 30mg I.m.. Follow-up was worked out monthly as well as the estimation of quality of life (QLQ-C30 questionnaire). Patients with negative somatostatin receptors (SSTR) detection were followed up in the same manner.RESULTS: Scintigraphy demonstrated SSTR in 61 patients. Thirty were randomized to receive only placebo and 31 only octreotide. A significantly higher survival time was observed for the octreotide group (49±6 wk)as compared to the control group (28±1 wk) and to the SSTR negative group (28±2 wk), LR=20.39, df=2,P<0.01. The octreotide group presented 68.5% lower hazard ratio [95% CI (47.4%-81.2%)]. During the first year, a 22%, 39% and 43% decrease in the QLQ-C30 score was observed in each group respectively.CONCLUSION: The proposed therapeutic approach has shown to improve the survival and quality of life in SSTR positive patients with advanced HCC.

  8. Women empowerment and the current use of long acting and permanent contraceptive: Evidence from 2010 Malawi Demographic and Health Survey.

    Science.gov (United States)

    Palamuleni, M E; Adebowale, A S

    2014-09-01

    Both contraceptive use and fertility rates are high fertility in Malawi. Status of women remains low and is believed to affect reproductive health decisions including use of Long Acting and Permanent Contraceptives Method (LAPCM). This study seeks to examine the relationship between women empowerment and LAPCM. A measure of women's empowerment is derived from the women's responses to questions on the number of household decisions in which the respondent participates, employment status, type of earnings, women's control over cash earnings and level of education. The study is based on a sub sample of 5,948 married women from the 2010 Malawi Demographic and Health Survey. Data was analysed using descriptive statistics, Chi-square and multinomial logistic regression models (α=5%). The prevalence of current use of LAPCM was 20.0% and increases with increasing empowerment level (pempowerment score of women who are currently using LAPCM were 38.53±6.2 years and 6.80±2.9 respectively. Urban women (22.2%) were more currently using LAPCM than rural women (19.4%) pWomen who belong to Seven Day Adventists/Baptist were 1.51(C.I=1.058-2.153; p=0.023) more likely and Muslims were 0.58(C.I=0.410-0.809; p=0.001) less likely to currently use LAPCM than Catholic women. Being in the richest wealth quintile (OR=1.91; C.I=1.362-2.665; pwomen who have access to FP programmes on media and increases consistently with increasing women empowerment level even when other potential confounding variables were used as control. In Malawi, LAPCM is still underutilized and more than half of the women are not adequately empowered. Women empowerment, wealth quintile and access to FP programmes are key factors influencing the use of LAPCM. Programmes that address these determinants are urgently needed in Malawi.

  9. Comparison of indacaterol with tiotropium or twice-daily long-acting β -agonists for stable COPD: a systematic review.

    Science.gov (United States)

    Rodrigo, Gustavo J; Neffen, Hugo

    2012-11-01

    Bronchodilators are central to the symptomatic management of patients with COPD.Previous data have shown that inhaled indacaterol improved numerous clinical outcomes over placebo. This systematic review explored the efficacy and safety of indacaterol in comparison with tiotropium or bid long-acting β 2 -agonists (TD-LABAs) for treatment of moderate to severe COPD. Randomized controlled trials were identified after a search of different databases of published and unpublished trials. Five trials (5,920 participants) were included. Compared with tiotropium, indacaterol showed statistically and clinically significant reductions in the use of rescue medication and dyspnea(43% greater likelihood of achieving a minimal clinically important difference [MCID] in the transitional dyspnea index [TDI]; number needed to treat for benefit [NNTB] 5 10). Additionally,the MCID in health status was more likely to be achieved with indacaterol than with tiotropium (OR = 1.43; 95% CI, 1.22–1.68; P = .00001; [NNTB ]= 10). Trough FEV 1 was significantly higher at the end of treatment with indacaterol than with TD-LABAs (80 mL, P = .00001). Similarly, indacaterol signifi cantly improved dyspnea (61% greater likelihood of achieving an MCID in TDI, P = .008) and health status (21% greater likelihood of achieving an MCID in St. George’s Respiratory Questionnaire, P 5 .04) than TD-LABA. Indacaterol showed similar levels of safety and tolerability to both comparators. Available evidence suggests that indacaterol may prove useful as an alternative to tiotropium or TD-LABA due to its effects on health status, dyspnea, and pulmonary function.

  10. Application of Implementation Science Methodology to Immediate Postpartum Long-Acting Reversible Contraception Policy Roll-Out Across States.

    Science.gov (United States)

    Rankin, Kristin M; Kroelinger, Charlan D; DeSisto, Carla L; Pliska, Ellen; Akbarali, Sanaa; Mackie, Christine N; Goodman, David A

    2016-11-01

    Purpose Providing long-acting reversible contraception (LARC) in the immediate postpartum period is an evidence-based strategy for expanding women's access to highly effective contraception and for reducing unintended and rapid repeat pregnancy. The purpose of this article is to demonstrate the application of implementation science methodology to study the complexities of rolling-out policies that promote immediate postpartum LARC use across states. Description The Immediate Postpartum LARC Learning Community, sponsored by the Association of State and Territorial Health Officials (ASTHO), is made up of multi-disciplinary, multi-agency teams from 13 early-adopting states with Medicaid reimbursement policies promoting immediate postpartum LARC. Partners include federal agencies and maternal and child health organizations. The Learning Community discussed barriers, opportunities, strategies, and promising practices at an in-person meeting. Implementation science theory and methods, including the Consolidated Framework for Implementation Research (CFIR), and a recent compilation of implementation strategies, provide useful tools for studying the complexities of implementing immediate postpartum LARC policies in birthing facilities across early adopting states. Assessment To demonstrate the utility of this framework for guiding the expansion of immediate postpartum LARC policies, illustrative examples of barriers and strategies discussed during the in-person ASTHO Learning Community meeting are organized by the five CFIR domains-intervention characteristics, outer setting, inner setting, characteristics of the individuals involved, and process. Conclusion States considering adopting policies can learn from ASTHO's Immediate Postpartum LARC Learning Community. Applying implementation science principles may lead to more effective statewide scale-up of immediate postpartum LARC and other evidence-based strategies to improve women and children's health.

  11. Beyond the era of NPH insulin--long-acting insulin analogs: chemistry, comparative pharmacology, and clinical application.

    Science.gov (United States)

    Owens, D R; Bolli, G B

    2008-10-01

    The new rDNA and DNA-derived "basal" insulin analogs, glargine and detemir, represent significant advancement in the treatment of diabetes compared with conventional NPH insulin. This review describes blood glucose homeostasis by insulin in people without diabetes and outlines the physiological application of exogenous insulin in patients with type 1 and type 2 diabetes. The requirements for optimal basal insulin treatment are discussed and the methods used in the evaluation of basal insulins are presented. An essential criterion in the development of an "ideal" basal insulin preparation is that the molecular modifications made to the human insulin molecule do not compromise safety. It is also necessary to obtain a clear understanding of the pharmacokinetic and pharmacodynamic characteristics of the two currently available basal insulin analogs. When comparing glargine and detemir, the different molar concentration ratios of the two insulin formulations should be considered along with the nonspecificity of assay systems used to determine insulin concentrations. However, euglycemic clamp studies in crossover study design provide a good basis for comparing the pharmacodynamic responses. When the latter is analyzed by results of intervention clinical trials, it is concluded that both glargine and detemir are superior to NPH in type 1 and type 2 diabetes. However, there is sufficient evidence to demonstrate that these two long-acting insulin analogs are different in both their pharmacokinetic and pharmacodynamic profiles. These differences should be taken into consideration when the individual analogs are introduced to provide basal insulin supplementation to optimize blood glucose control in patients with type 1 and type 2 diabetes as well. PubMed-Medline was searched for articles relating to pharmacokinetics and pharmacodynamics of glargine and detemir. Articles retrieved were reviewed and selected for inclusion if (1) the euglycemic clamp method was used with a

  12. Assessment of effectiveness measures in patients with schizophrenia initiated on risperidone long-acting therapy: the SOURCE study results

    Directory of Open Access Journals (Sweden)

    Dirani Riad D

    2011-10-01

    Full Text Available Abstract Background To evaluate effectiveness outcomes in a real-world setting in patients with schizophrenia initiating risperidone long-acting therapy (RLAT. Methods This was a 24-month, multicenter, prospective, longitudinal, observational study in patients with schizophrenia who were initiated on RLAT. Physicians could change treatment during the study as clinically warranted. Data were collected at baseline and subsequently every 3 months up to 24 months. Effectiveness outcomes included changes in illness severity as measured by Clinical Global Impression-Severity (CGI-S scale; functional scores as measured by Personal and Social Performance (PSP scale, Global Assessment of Functioning (GAF, and Strauss-Carpenter Levels of Functioning (LOF; and health status (Medical Outcomes Survey Short Form-36 [SF-36]. Life-table methodology was used to estimate the cumulative probability of relapse over time. Adverse events were evaluated for safety. Results 532 patients were enrolled in the study; 209 (39.3% completed the 24-month study and 305 (57.3% had at least 12 months of follow-up data. The mean (SD age of patients was 42.3 (12.8 years. Most patients were male (66.4% and either Caucasian (60.3% or African American (23.7%. All changes in CGI-S from baseline at each subsequent 3-month follow-up visit were statistically significant (p Conclusions Patients with schizophrenia who were initiated on RLAT demonstrated improvements in measures of effectiveness within 3 months, which persisted over 24 months. Trial Registration ClinicalTrials.gov: NCT00246194

  13. A phase 2 trial of long-acting TransCon growth hormone in adult GH deficiency.

    Science.gov (United States)

    Höybye, Charlotte; Pfeiffer, Andreas F H; Ferone, Diego; Christiansen, Jens Sandahl; Gilfoyle, David; Christoffersen, Eva Dam; Mortensen, Eva; Leff, Jonathan A; Beckert, Michael

    2017-04-01

    TransCon growth hormone is a sustained-release human growth hormone prodrug under development in which unmodified growth hormone is transiently linked to a carrier molecule. It is intended as an alternative to daily growth hormone in the treatment of growth hormone deficiency. This was a multi-center, randomized, open-label, active-controlled trial designed to compare the safety (including tolerability and immunogenicity), pharmacokinetics and pharmacodynamics of three doses of weekly TransCon GH to daily growth hormone (Omnitrope). Thirty-seven adult males and females diagnosed with adult growth hormone deficiency and stable on growth hormone replacement therapy for at least 3 months were, following a wash-out period, randomized (regardless of their pre-study dose) to one of three TransCon GH doses (0.02, 0.04 and 0.08 mg GH/kg/week) or Omnitrope 0.04 mg GH/kg/week (divided into 7 equal daily doses) for 4 weeks. Main outcomes evaluated were adverse events, immunogenicity and growth hormone and insulin-like growth factor 1 levels. TransCon GH was well tolerated; fatigue and headache were the most frequent drug-related adverse events and reported in all groups. No lipoatrophy or nodule formation was reported. No anti-growth hormone-binding antibodies were detected. TransCon GH demonstrated a linear, dose-dependent increase in growth hormone exposure without accumulation. Growth hormone maximum serum concentration and insulin-like growth factor 1 exposure were similar after TransCon GH or Omnitrope administered at comparable doses. The results suggest that long-acting TransCon GH has a profile similar to daily growth hormone but with a more convenient dosing regimen. These findings support further TransCon GH development.

  14. Improvement in hyperprolactinemia and reproductive comorbidities in patients with schizophrenia switched from conventional antipsychotics or risperidone to olanzapine.

    Science.gov (United States)

    Kinon, Bruce J; Ahl, Jonna; Liu-Seifert, Hong; Maguire, Gerald A

    2006-06-01

    This open-label, prospective, 4-month study in hyperprolactinemic patients with schizophrenia explored whether prolactin levels decrease after switching antipsychotic therapy to olanzapine. A secondary objective was to determine if reproductive morbidities and sexual dysfunction occurring with hyperprolactinemia improved with prolactin normalization. Clinically stable patients with schizophrenia, who had hyperprolactinemia defined as >18.8 ng/ml for males and >24.2 ng/ml for females, were randomized to: remain on current therapy (n=27) or switch to olanzapine, 5-20 mg/day, (n=27). Baseline prolactin levels in female patients randomized to receive olanzapine (n=14) were 66.3+/-38.7 ng/ml and were 82.0+/-37.6 (p=.32) in those remaining on their pre-study antipsychotic medication (n=14). In male patients, baseline prolactin levels were 33.7+/-12.1 and 33.5+/-13.8 ng/ml (p=.97), respectively, for those randomized to olanzapine (n=13) or remaining on pre-study treatment (n=13). At study end, patients switched to olanzapine experienced significant reductions in mean serum prolactin levels of 19.8+/-18.1 ng/ml in males (p=.02), and 32.3+/-47.5 ng/ml in females (p=.01), but prolactin continued to be elevated in patients who remained on pre-study antipsychotic treatment. After switching to olanzapine treatment, male patients experienced significantly (p=.03) increased free testosterone levels but there were no significant improvements in total testosterone levels; some female patients experienced improved menstrual cycling, as well as resolution of galactorrhea and gynecomastia, and sexual functioning was significantly improved in both genders. Patients switched to olanzapine, as well as those remaining on their pre-study medication, maintained clinical stability, their symptoms continued to improve, although there were no significant between-treatment differences in improvement. Treatment-emergent adverse events did occur in both treatment groups; however, they were not

  15. Olanzapine-induced hepatopathy in albino rats: A newer model for screening putative hepatoprotective agents, namely silymarin

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    Sengupta Parama

    2010-01-01

    Full Text Available Backgrounds: This study was conducted to establish olanzapine-induced hepatopathy in Wistar albino rats as a newer model to screen putative hepatoprotective agents namely silymarin. Materials and Methods: Albino rats were divided into three groups, namely vehicle control group (CG, olanzapine-treated group (OZ, and olanzapine plus silymarin (OZS treated groups. Both the OZ and OZS groups were treated with the same dose of intraperitoneal olanzapine for 6 weeks and group OZS additionally received oral silymarin. Baseline and terminal hepatic enzymes (SGOT, SGPT, and ALP were measured in all three groups. Results: Histopathological examination of livers of both OZ and OZS groups showed degenerative changes, whereas those of control group showed normal architecture. Liver enzyme levels showed statistically significant rise in comparison to the control group as well as the respective base line values in both the test groups, but the differences in the rise of liver enzymes between the two test groups were not statistically significant. Conclusion: Olanzapine-induced hepatopathy in rats can be used as a model for screening putative hepatoprotective agents and in our setting silymarin has failed to provide any hepatoprotection.

  16. Intramuscular Olanzapine in the Management of Behavioral and Psychological Symptoms in Hospitalized Older Adults: A Retrospective Descriptive Study

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    Silvia Duong

    2015-01-01

    Full Text Available Background. While behavioral and psychological symptoms are frequent in hospitalized older adults with dementia or delirium, data supporting the off-label use of intramuscular atypical antipsychotics remain scarce. We examined the use of short-acting intramuscular (IM olanzapine in hospitalized older adults to manage behavioral and psychological symptoms. Methods. A retrospective observational study of inpatients 65 years or older with at least one order for olanzapine IM during admission in urban Ontario Canada was conducted. Patient demographics, prescriptions for olanzapine IM, reason for administration, perceived effectiveness, adverse events, concurrently prescribed psychotropics, comorbidities, and patient discharge destination were recorded. Results. Among 82 patients aged 65–96 years (mean ± SD 79.3 ± 7.7 85 cases were identified. Cognitive impairment or dementia affected 63.5% and 50.6% had comorbidities. Olanzapine IM was ordered 102 times and 34 patients (41% received at least one dose. The intended efficacy was achieved in 79.4% of 78 cases of 124 doses given (62.9%. Fourteen (41% patients who received doses experienced adverse events, with sedation and hypotension being the most common. Conclusions. Olanzapine IM appears effective in hospitalized older adults but is associated with potential adverse events. Structured monitoring and documentation are needed to ensure safe use in this high-risk population.

  17. Pharmaco-epidemiological description of the population of the Marche Region (central Italy treated with the antipsychotic drug olanzapine

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    Fiorenzo Mignini

    2013-03-01

    Full Text Available BACKGROUND. In Italy, even though olanzapine has been discouraged for treatment of behaviour disorders in older patients affected by dementia, some physicians chose to prescribe for them. In response to this situation, the Italian Drug Agency (Agenzia Italiana del Farmaco, AIFA promulgated a cautionary note. MATERIALS AND METHODS. This study examined epidemiological indices for olanzapine prescriptions between 2004 and 2007 in the Marche Region of central Italy and in its provinces, to assess physician compliance with the AIFA note, and to determine whether there were differences in drug prescription between populations of the same territory, or differences based on gender or age group. RESULTS. Our analyses revealed high olanzapine use among young men and mature women, suggesting that these groups are most prone to psychotic symptoms. Analysis revealed that olanzapine prescription in elderly patients was reduced in some provinces, in line with the AIFA note. CONCLUSIONS. Prudent use of olanzapine prescription, in compliance with the AIFA note, was noted throughout the Region. Furthermore, this work offers details that may be useful in future studies of adverse drug reactions.

  18. Chronic betahistine co-treatment reverses olanzapine's effects on dopamine D₂ but not 5-HT2A/2C bindings in rat brains.

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    Lian, Jiamei; Huang, Xu-Feng; Pai, Nagesh; Deng, Chao

    2015-01-02

    Olanzapine is widely prescribed for treating schizophrenia and other mental disorders, although it leads to severe body weight gain/obesity. Chronic co-treatment with betahistine has been found to significantly decrease olanzapine-induced weight gain; however, it is not clear whether this co-treatment affects the therapeutic effects of olanzapine. This study investigated the effects of chronic treatment of olanzapine and/or betahistine on the binding density of the serotonergic 5-HT2A (5-HT2AR) and 5-HT2C (5-HT2CR) receptors, 5-HT transporter (5-HTT), and dopaminergic D₂ receptors (D₂R) in the brain regions involved in antipsychotic efficacy, including the prefrontal cortex (PFC), cingulate cortex (Cg), nucleus accumbens (NAc), and caudate putamen (CPu). Rats were treated with olanzapine (1 mg/kg, t.i.d.) or vehicle for 3.5 weeks, and then olanzapine treatment was withdrawn for 19 days. From week 6, the two groups were divided into 4 groups (n=6) for 5 weeks' treatment: (1) olanzapine-only (1 mg/kg, t.i.d.), (2) betahistine-only (9.6 mg/kg, t.i.d.), (3) olanzapine and betahistine co-treatment (O+B), and (4) vehicle. Compared to the control, the olanzapine-only treatment significantly decreased the bindings of 5-HT2AR, 5-HT2CR, and 5-HTT in the PFC, Cg, and NAc. Similar changes were observed in the rats receiving the O+B co-treatment. The olanzapine-only treatment significantly increased the D₂R binding in the Cg, NAc, and CPu, while the betahistine-only treatment reduced D₂R binding. The co-treatment of betahistine reversed the D₂R bindings in the NAc and CPu that were increased by olanzapine. Therefore, chronic O+B co-treatment has similar effects on serotonin transmission as the olanzapine-only treatment, but reverses the D₂R that is up-regulated by chronic olanzapine treatment. The co-treatment maintains the therapeutic effects of olanzapine but decreases/prevents the excess weight gain.

  19. Pharmacokinetic and pharmacodynamic properties of a long-acting formulation of the new somatostatin analogue, lanreotide, in normal healthy volunteers.

    Science.gov (United States)

    Kuhn, J M; Legrand, A; Ruiz, J M; Obach, R; De Ronzan, J; Thomas, F

    1994-01-01

    1. The aims of the study were to assess the pharmacokinetic parameters and the hormonal effects of the slow-release formulation of the somatostatin analogue (SR-L) in normal male volunteers. 2. Eight healthy males were studied. For the determination of basal values blood was sampled before the injection of vehicle and then every other hour for 8 h in order to measure plasma GH, prolactin (PRL), TSH, free thyroxin (fT4), insulin and glucagon levels. Plasma insulin-like growth factor 1 (IGF-1) levels were measured on a single sample. On day 1 of the study, 30 mg SR-L was administered intramuscularly. Blood was drawn just before injection and then every other hour for a period of 8 h. Thereafter, blood was sampled three times a week for 3 weeks in order to measure lanreotide, IGF-1, TSH, fT4 and PRL concentrations. Plasma GH was determined on days 6 and 11 of the study. 3. Plasma lanreotide concentrations rose to 38.3 +/- 4.1 ng ml-1 2 h following injection. The levels then progressively decreased, remaining above 1.5 ng ml-1 until day 11 and reaching 0.92 +/- 0.28 ng ml-1 2 weeks after injection. The apparent plasma half-life and mean residence time were 4.52 +/- 0.50 and 5.48 +/- 0.51 days respectively. 4. By comparison with the control day, plasma insulin concentrations only decreased 2 h following injection, whereas plasma glucagon did not change at any time. 5. Plasma TSH concentrations were significantly (P < 0.01) reduced from 2 h to day 4 following SR-L injection.2+ ' PMID:7826822

  20. Long-acting methylphenidate formulations in the treatment of attention-deficit/hyperactivity disorder: a systematic review of head-to-head studies

    Science.gov (United States)

    2013-01-01

    Background The stimulant methylphenidate (MPH) has been a mainstay of treatment for attention-deficit/hyperactivity disorder (ADHD) for many years. Owing to the short half-life and the issues associated with multiple daily dosing of immediate-release MPH formulations, a new generation of long-acting MPH formulations has emerged. Direct head-to-head studies of these long-acting MPH formulations are important to facilitate an evaluation of their comparative pharmacokinetics and efficacy; however, to date, relatively few head-to-head studies have been performed. The objective of this systematic review was to compare the evidence available from head-to-head studies of long-acting MPH formulations and provide information that can guide treatment selection. Methods A systematic literature search was conducted in MEDLINE and PsycINFO in March 2012 using the MeSH terms: attention deficit disorder with hyperactivity/drug therapy; methylphenidate/therapeutic use and All Fields: Concerta; Ritalin LA; OROS and ADHD; Medikinet; Equasym XL and ADHD; long-acting methylphenidate; Diffucaps and ADHD; SODAS and methylphenidate. No filters were applied and no language, publication date or publication status limitations were imposed. Articles were selected if the title indicated a comparison of two or more long-acting MPH preparations in human subjects of any age; non-systematic review articles and unpublished data were not included. Results Of 15,295 references returned in the literature search and screened by title, 34 articles were identified for inclusion: nine articles from pharmacokinetic studies (nine studies); nine articles from laboratory school studies (six studies); two articles from randomized controlled trials (two studies); three articles from switching studies (two studies) and three articles from one observational study. Conclusions Emerging head-to-head studies provide important data on the comparative efficacy of the formulations available. At a group level, efficacy

  1. Clinical pharmacokinetics of AZD3199, an inhaled ultra-long-acting β2-adrenoreceptor agonist (uLABA

    Directory of Open Access Journals (Sweden)

    Bjermer L

    2015-02-01

    Full Text Available Leif Bjermer,1 Piotr Kuna,2 Carin Jorup,3 Thomas Bengtsson,4 Johan Rosenborg4 1Department of Respiratory Medicine and Allergology, University Hospital, Lund, Sweden; 2Department of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, Poland; 3AstraZeneca R&D, Mölndal, Sweden; 4StatMind, Lund, Sweden Objective: The clinical pharmacokinetics of AZD3199, an ultra-long-acting β2-agonist, were investigated in healthy volunteers and patients with asthma or chronic obstructive pulmonary disease (COPD. Materials and methods: Five studies are presented: one single ascending dose study in healthy Caucasian males; two multiple ascending dose studies in healthy males, one in Caucasians and one in Japanese; a Phase IIA asthma study; and a Phase IIB COPD study. Subjects received AZD3199 via a Spira nebulizer (Turbuhaler; equivalent delivered doses 5–3200 µg or Turbuhaler (single delivered doses of 120–1920 µg or repeated delivered once-daily doses 240–1,680 µg. AZD3199 pharmacokinetics were assessed using total plasma concentration and urinary excretion, and tolerability using adverse events, clinical laboratory tests, and physical examinations. Results: AZD3199 appeared rapidly in the systemic circulation following single and multiple dosing in healthy volunteers and patients (maximum plasma concentration within 30 minutes, with dose-proportional time-independent pharmacokinetics. Plasma exposure to unmetabolized drug was similar in healthy volunteers and patients with asthma, but relatively lower in patients with COPD. Estimated terminal half-life was up to 142 hours in healthy Caucasian males. AZD3199 was well tolerated and showed no or at most mild systemic effects. Conclusion: AZD3199 plasma exposure in healthy volunteers and patients suggested linear pharmacokinetics and a long half-life. Systemic availability was similar in healthy subjects and patients with asthma, but was lower in patients

  2. Changes in Use of Long-Acting Reversible Contraceptive Methods Among U.S. Women, 2009–2012

    Science.gov (United States)

    Kavanaugh, Megan L.; Jerman, Jenna; Finer, Lawrence B.

    2016-01-01

    OBJECTIVE To examine current levels, current correlates of, and changes in long-acting reversible contraceptive (LARC) use, including intrauterine devices and implants, among females aged 15–44 years using contraception between 2008–2010 and 2011–2013 with specific attention to associations between race, income, and age and their LARC use. METHODS We analyzed data from two rounds of the National Survey of Family Growth, nationally representative samples of females aged 15–44 years, consisting of 6,428 females in 2008–2010 and 5,601 females in 2011–2013. We conducted simple and multivariable logistic regression analyses with adjustments for the sampling design to identify demographic characteristics predictive of LARC use and changes in these patterns between the two time periods. In this cross-sectional, descriptive study, our primary outcome of interest was current prevalence of LARC use among all contraceptive users at the time of the interview. RESULTS The prevalence of LARC use among contracepting U.S. females increased from 8.5% in 2009 to 11.6% in 2012 (P<.01). The most significant increases occurred among Hispanic females (from 8.5% to 15.1%), those with private insurance (7.1–11.1%), those with fewer than two sexual partners in the previous year (9.2–12.4%), and those who were nulliparous (2.1–5.9%) (all P<.01). In multivariable analyses adjusting for key demographic characteristics, the strongest associations with LARC use in 2012 were parity (adjusted odds ratios [ORs] 4.3–5.5) and having a history of stopping non-LARC hormonal use (adjusted OR 1.9). Women aged 35–44 years (adjusted OR 0.3) were less likely to be LARC users than their counterparts (all P<.001). Poverty status was not associated with LARC use. There were no differences in discontinuation of LARC methods resulting from dissatisfaction between minority women and non-Hispanic white women. CONCLUSION During the most recent time period surveyed, use of LARC methods

  3. Long-acting bronchodilator use after hospitalization for COPD: an observational study of health insurance claims data

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    Baker CL

    2014-05-01

    Full Text Available Christine L Baker,1 Kelly H Zou,1 Jun Su21Pfizer Inc., New York, NY, USA; 2Boehringer-Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USABackground: Treatment of stable chronic obstructive pulmonary disease (COPD with long-acting bronchodilator (LABD medications is recommended by the 2014 Global initiative for chronic Obstructive Lung Disease (GOLD guidelines. The primary objective of this study was to examine LABD prescription fills after a COPD-related hospitalization.Methods: This retrospective observational study used claims from Truven Health MarketScan® Commercial and Medicare Supplemental databases. Patients (age ≥40, commercial; age ≥65, Medicare supplemental had a first hospitalization with a primary COPD diagnosis between April 1, 2009 and June 30, 2011 (index hospitalization and were continuously enrolled for 1 year before and 9 months after hospitalization. Patients were categorized according to pre-index and/or post-index pharmacy claims.Results: A total of 27,738 patients had an index hospitalization and met inclusion/exclusion criteria. Of those, 19,783 patients had COPD as a primary or secondary diagnosis during the year before index hospitalization and were included in the analysis. Approximately one quarter of the patients (26.32% did not fill a prescription for an LABD or short-acting bronchodilator both 90 days before and 90 days after hospitalization. During the 90-day pre-index period, 40.57% of patients filled an LABD (with or without a short-acting bronchodilator prescription. Over half of the patients (56.88% filled an LABD prescription at some point during the 180-day post-index period, but, of those, a significantly greater proportion of patients filled an LABD prescription in the 1- to 90-day post-index period than in the 91- to 180-day post-index period (51.27% versus 43.66%; P<0.0001.Conclusion: A significant proportion of COPD patients in this study did not fill an LABD prescription before hospitalization for

  4. LC-MS/MS method applied to preclinical pharmacokinetic investigation of olanzapine-loaded lipid-core nanocapsules

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    Frantiescoli A. Dimer

    2014-01-01

    Full Text Available In spite of different methods reported in the literature to determine olanzapine in biological fluids, all of them used high volumes of plasma. Therefore, the purpose of this paper was to develop an LC-MS/MS method using small plasma volume (0.1 mL to apply in a preclinical pharmacokinetic investigation. The method was linear over the concentration ranges of 10 - 1000 ng mL-1. Extraction recoveries, stability, and validation parameters were evaluated. Results were within the acceptable limits of international guidelines. A significant decrease in clearance led to a significant 2.26-times increase in AUC0 - 6h of olanzapine-loaded lipid-core nanocapsules compared with free-olanzapine.

  5. A European multicentre survey of impulse control behaviours in Parkinson's disease patients treated with short- and long-acting dopamine agonists

    DEFF Research Database (Denmark)

    Rizos, A; Sauerbier, A; Antonini, A

    2016-01-01

    BACKGROUND AND PURPOSE: Impulse control disorders (ICDs) in Parkinson's disease (PD) are associated primarily with dopamine agonist (DA) use. Comparative surveys of clinical occurrence of impulse control behaviours on longer acting/transdermal DA therapy across age ranges are lacking. The aim...... on medical records and clinical interviews of patients initiating or initiated on DA treatment (both short- and long-acting, and transdermal) across a broad range of disease stages and age groups was performed. RESULTS: Four hundred and twenty-five cases were included [mean age 68.3 years (range 37-90), mean...... release PPX (PPX-IR) (19.0%; P therapy due to ICDs were low. CONCLUSION: Our data suggest a relatively low rate of ICDs with long-acting or transdermal DAs, however these preliminary observational data need to be confirmed with prospective studies controlling...

  6. Demand for long acting contraceptive methods among married HIV positive women attending care at public health facilities at Bahir Dar City, Northwest Ethiopia.

    Science.gov (United States)

    Gelagay, Abebaw Addis; Koye, Digsu Negese; Yeshita, Hedija Yenus

    2015-08-27

    The use of long acting contraceptive methods (LACMs) is one of the strategies for preventing mother-to-child transmission (MTCT) of HIV. Studies noted that significant proportion of unintended pregnancy among HIV positive women was due to contraceptive failure mainly of short term contraceptives. This highlights the need to use most effective types of modern contraception, long acting contraceptive. However, studies conducted on demand for long acting contraceptive methods in this particular group of people are scarce in Ethiopia. This study aimed to assess demand for long acting contraceptive methods and associated factors among married reproductive age women attending care at Antiretroviral treatment (ART) clinics in public health institutions at Bahir Dar City, Northwest Ethiopia. Institution-based cross-sectional study was conducted among 654 systematically selected women attending care in ART clinics in public health facilities at Bahir Dar city from March to April, 2014. A structured and pretested interviewer administered questionnaire was used to collect data. Data were entered using EPI info version 3.5.3 and then exported to SPSS version 16 for analysis. Descriptive statistics were used to describe the socio-demographic and economic characteristics of the study participants. Logistic regression analyses were employed to identify factors associated with demand for long acting contraceptive methods. Odds ratios with 95 % CI were used to assess the presence and strength of association. A total of 654 respondents have participated in the study (response rate 99. 09 %). The demand for long acting contraceptive methods was 36.7 % (95 % CI: 33.2 %, 40.6 %). The odds of demand for LACMs among HIV positive women who were living in urban were three times [AOR = 3.05, 95 % CI: 1.34, 6.89] higher than those who were living in rural. The odds of demand for LACMs among the respondents who were in elementary educational level were two times [AOR = 2.31, 95

  7. Cost-effectiveness model comparing olanzapine and other oral atypical antipsychotics in the treatment of schizophrenia in the United States

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    Smolen Lee J

    2009-04-01

    Full Text Available Abstract Background Schizophrenia is often a persistent and costly illness that requires continued treatment with antipsychotics. Differences among antipsychotics on efficacy, safety, tolerability, adherence, and cost have cost-effectiveness implications for treating schizophrenia. This study compares the cost-effectiveness of oral olanzapine, oral risperidone (at generic cost, primary comparator, quetiapine, ziprasidone, and aripiprazole in the treatment of patients with schizophrenia from the perspective of third-party payers in the U.S. health care system. Methods A 1-year microsimulation economic decision model, with quarterly cycles, was developed to simulate the dynamic nature of usual care of schizophrenia patients who switch, continue, discontinue, and restart their medications. The model captures clinical and cost parameters including adherence levels, relapse with and without hospitalization, quality-adjusted life years (QALYs, treatment discontinuation by reason, treatment-emergent adverse events, suicide, health care resource utilization, and direct medical care costs. Published medical literature and a clinical expert panel were used to develop baseline model assumptions. Key model outcomes included mean annual total direct cost per treatment, cost per stable patient, and incremental cost-effectiveness values per QALY gained. Results The results of the microsimulation model indicated that olanzapine had the lowest mean annual direct health care cost ($8,544 followed by generic risperidone ($9,080. In addition, olanzapine resulted in more QALYs than risperidone (0.733 vs. 0.719. The base case and multiple sensitivity analyses found olanzapine to be the dominant choice in terms of incremental cost-effectiveness per QALY gained. Conclusion The utilization of olanzapine is predicted in this model to result in better clinical outcomes and lower total direct health care costs compared to generic risperidone, quetiapine, ziprasidone, and

  8. Predictors of antipsychotic monotherapy with olanzapine during a 1-year naturalistic study of schizophrenia patients in Japan

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    Ye W

    2012-01-01

    Full Text Available Wenyu Ye1, Haya Ascher-Svanum2, Jennifer A Flynn3, Yuka Tanji3, Michihiro Takahashi3,41Lilly Suzhou Pharmaceutical Co, Shanghai, People's Republic of China; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, 4Terauchi-Takahashi Psychiatric Clinic, Ashiya, JapanPurpose: Although expert guidelines for the treatment of schizophrenia recommend antipsychotic monotherapy, the use of antipsychotic polypharmacy is common. This study identified characteristics that differentiate patients with schizophrenia who are treated with olanzapine monotherapy versus polypharmacy in usual care in Japan.Patients and methods: In a large (N = 1850 prospective, observational study, Japanese patients with schizophrenia who initiated treatment with olanzapine were followed for 1 year. Consistent with past research, antipsychotic polypharmacy was defined as the concurrent use of olanzapine and another antipsychotic for at least 60 days. Switching was defined as discontinuing a prior antipsychotic therapy rather than augmenting the medication regimen. Predictors of antipsychotic monotherapy were based on information available at the time of olanzapine initiation. Baseline characteristics were compared using t-tests and Χ2 tests. Stepwise logistic regression was used to identify independent predictors of monotherapy.Results: Patients treated with olanzapine monotherapy (43.2% differed from those treated with antipsychotic polypharmacy (56.8% on demographics, treatment history, baseline symptom levels, functional levels, and treatment-emergent adverse events. Stepwise logistic regression identified multiple variables that significantly predicted monotherapy: older age, shorter duration of schizophrenia, outpatient status, comorbid medical conditions, lower body mass index, no prior anticholinergic use, no prior mood stabilizer use, and switching from a previous antipsychotic (typical or atypical

  9. Once-daily glycopyrronium bromide, a long-acting muscarinic antagonist, for chronic obstructive pulmonary disease: a systematic review of clinical benefit

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    Ulrik CS

    2012-09-01

    Full Text Available Charlotte Suppli UlrikDepartment of Pulmonary Medicine, Hvidovre Hospital and University of Copenhagen, Copenhagen, DenmarkBackground: Long-acting bronchodilators are central in the pharmacological management of patients with chronic obstructive pulmonary disease (COPD. The aim of this systematic review is to provide an overview of the studies evaluating the safety and clinical efficacy of inhaled glycopyrronium bromide, a novel long-acting muscarinic antagonist, in patients with COPD.Methods: This study was performed as a systematic literature review.Results: Inhaled glycopyrronium bromide seems to be a safe and well tolerated long-acting muscarinic antagonist with a fast onset of action. In patients suffering from moderate to severe COPD, glycopyrronium bromide has clinically important effects on level of forced expiratory volume in one second, use of relief medication, percentage of days with no use of rescue medication, daytime dyspnea scores, and probably also on health status. Furthermore, in this group of patients, glycopyrronium bromide has beneficial effects on dynamic hyperinflation and exercise tolerance. Glycopyrronium bromide has been shown to reduce the rate of exacerbations in patients with moderate to severe COPD, but long-term controlled trials with exacerbation rate as the primary outcome variable have not been published yet.Conclusion: Once-daily inhaled glycopyrronium bromide has characteristics important for use in COPD, including a fast onset of action, sustained 24-hour bronchodilatation, and improvement in exercise tolerance, and therefore appears to have the potential for a significant role in the future management of COPD.Keywords: chronic obstructive pulmonary disease, glycopyrronium bromide, long-acting bronchodilators

  10. Pneumonia and pneumonia related mortality in patients with COPD treated with fixed combinations of inhaled corticosteroid and long acting β2 agonist: observational matched cohort study (PATHOS)

    OpenAIRE

    Janson, Christer; Larsson, Kjell; Lisspers, Karin H; Ställberg, Björn; Stratelis, Georgios; Goike, Helena; Jorgensen, Leif; Johansson, Gunnar

    2013-01-01

    Objective To investigate the occurrence of pneumonia and pneumonia related events in patients with chronic obstructive pulmonary disease (COPD) treated with two different fixed combinations of inhaled corticosteroid/long acting beta(2) agonist. Design Observational retrospective pairwise cohort study matched (1:1) for propensity score. Setting Primary care medical records data linked to Swedish hospital, drug, and cause of death registry data for years 1999-2009. Participants Patients with CO...

  11. Risk of Pneumonia with Inhaled Corticosteroid versus Long-Acting Bronchodilator Regimens in Chronic Obstructive Pulmonary Disease: A New-User Cohort Study

    OpenAIRE

    DiSantostefano, Rachael L; Tim Sampson; Hoa Le; David Hinds; Davis, Kourtney J; Nawar Diar Bakerly

    2014-01-01

    INTRODUCTION: Observational studies using case-control designs have showed an increased risk of pneumonia associated with inhaled corticosteroid (ICS)-containing medications in patients with chronic obstructive pulmonary disease (COPD). New-user observational cohort designs may minimize biases associated with previous case-control designs. OBJECTIVE: To estimate the association between ICS and pneumonia among new users of ICS relative to inhaled long-acting bronchodilator (LABD) monotherapy. ...

  12. Comparative efficacy of inhaled corticosteroid and long-acting beta agonist combinations in preventing COPD exacerbations: a Bayesian network meta-analysis

    OpenAIRE

    Oba, Yuji; Lone, Nazir

    2014-01-01

    Yuji Oba, Nazir A Lone University of Missouri, School of Medicine, Division of Pulmonary, Critical Care and Environmental Medicine, Columbia, MO, USA Background: A combination therapy with inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA) is recommended in severe chronic obstructive pulmonary disease (COPD) patients experiencing frequent exacerbations. Currently, there are five ICS/LABA combination products available on the market. The purpose of this study was to systematic...

  13. Pharmacogenetics and olanzapine treatment: CYP1A2*1F and serotonergic polymorphisms influence therapeutic outcome.

    Science.gov (United States)

    Laika, B; Leucht, S; Heres, S; Schneider, H; Steimer, W

    2010-02-01

    Psychiatric pharmacotherapy with olanzapine is commonplace. We investigated the influence of CYP1A2*1F (-163A, rs762551) and serotonergic polymorphisms on olanzapine serum concentrations and clinical outcome in a naturalistic clinical setting. Included were 124 Caucasian psychiatric inpatients treated with olanzapine for at least 4 weeks with steady-state serum concentrations available for 73 patients. The CYP1A2*1F polymorphism was reported to affect the inducibility of CYP1A2. In our study population, CYP1A2*1F/*1F genotype alone resulted in a 22% reduction of dose-/body weight-normalized olanzapine serum concentrations compared to homo- and heterozygote carriers of CYP1A2*1A (both groups without inducers). This effect was independent of the well-known effect of inducing agents (here tobacco smoke and carbamazepine which led to on average 28% lower concentrations in CYP1A2*1A carriers and 26% lower concentrations in CYP1A2*1F/*1F carriers). Consistently, patients with the CYP1A2*1F/*1F genotype taking inducers had 22% lower concentrations compared to CYP1A2*1A carriers taking inducers. The influence of genotype alone remained significant after Bonferroni's post hoc test. Higher olanzapine concentrations were significantly correlated with better improvement of paranoid and depressive symptoms in patients with schizophrenic disorders (Spearman's r=0.5, P=0.026 and P=0.006, respectively). No relationship between serum concentrations and the side effects (DOTES) score was detected. However, patients with the 5-HTR2A intron 2 (rs7997012) AA genotype suffered from more pronounced side effects compared to carriers of the GA or GG genotype (P=0.018 and P=0.002). Short-term weight gain under olanzapine therapy was significantly lower for 5-HTR2C -759 T-allele carriers (P=0.011). Our data suggest that the CYP1A2*1F/*1F genotype exhibits a significant influence on olanzapine concentrations independent of other inducing factors. Thus, CYP1A2*1F genotyping may be useful for

  14. Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide.

    Science.gov (United States)

    Cebon, J; Findlay, M; Hargreaves, C; Stockler, M; Thompson, P; Boyer, M; Roberts, S; Poon, A; Scott, A M; Kalff, V; Garas, G; Dowling, A; Crawford, D; Ring, J; Basser, R; Strickland, A; Macdonald, G; Green, M; Nowak, A; Dickman, B; Dhillon, H; Gebski, V

    2006-10-09

    Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the feasibility, safety, and activity of long-acting octreotide in advanced HCC; to identify the best method for assessing somatostatin receptor expression; to relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty-three patients with advanced HCC received intramuscular long-acting octreotide 20 mg monthly until progression or toxicity. Median age was 67 years (range 28-81 years), male 81%, Child-Pugh A 83%, and B 17%. The aetiologies of chronic liver disease were alcohol (22%), viral hepatitis (44%), and haemochromatosis (6%). Prior treatments for HCC included surgery (8%), chemotherapy (2%), local ablation (11%), and chemoembolisation (6%). One patient had an objective partial tumour response (2%, 95% CI 0-9%). Serum alpha-fetoprotein levels decreased more than 50% in four (6%). Median survival was 8 months. Thirty four of 61 patients (56%) had receptor expression detected by scintigraphy; no clear relationship with clinical outcomes was identified. There were few grade 3 or 4 toxicities: hyperglycaemia (8%), hypoglycaemia (2%), diarrhoea (5%), and anorexia (2%). Patients reported improvements in some symptoms, but no major changes in quality of life were detected. Long-acting octreotide is safe in advanced HCC. We found little evidence of anticancer activity. A definitive randomised trial would identify whether patients benefit from this treatment in other ways.

  15. Primary care physician attitudes and perceptions of the impact of FDA-proposed REMS policy on prescription of extended-release and long-acting opioids

    Directory of Open Access Journals (Sweden)

    Salinas GD

    2012-10-01

    Full Text Available Gregory D Salinas, Caroline O Robinson, Maziar AbdolrasulniaCE Outcomes LLC, Birmingham, AL, USAAbstract: With increasing numbers of patients experiencing chronic pain, opioid therapy is becoming more common, leading to increases in concern about issues of abuse, diversion, and misuse. Further, the US Food and Drug Administration recently released a statement notifying sponsors and manufacturers of extended-release and long-acting opioids of the need to develop Risk Evaluation and Mitigation Strategies (REMS programs in order to ensure that the benefits of this therapy choice outweigh the potential risks. There is little research on physician opinions concerning opioid-prescribing and education policies. To assess attitudes surrounding new opioid policies, a survey was designed and distributed to primary care physicians in October 2011. Data collected from 201 primary care physicians show that most are not familiar with the REMS requirements proposed by the Food and Drug Administration for extended-release and long-acting opioids; there is no consensus among primary care physicians on the impact of prescribing requirements on patient education and care; and increasing requirements for extended-release and long-acting opioid education may decrease opioid prescribing. Physician attitudes toward increased regulatory oversight of opioid therapy prescriptions should be taken into consideration by groups developing these interventions to ensure that they do not cause undue burden on already busy primary care physicians.Keywords: REMS, opioids, attitudes, survey

  16. Gabapentin adjunctive to risperidone or olanzapine in partially responsive schizophrenia: an open-label pilot study

    Directory of Open Access Journals (Sweden)

    Adel Gabriel

    2010-10-01

    Full Text Available Adel GabrielDepartments of Psychiatry and Community Health Sciences, University of Calgary, Alberta, CanadaBackground: There is a great need in the treatment of schizophrenia for a drug, or drug ­combinations, to improve clinical response with fewer serious side effects. The objective of this study was to explore the therapeutic effects and tolerability of the anticonvulsant gabapentin as an adjunctive in the treatment of patients with partially responsive schizophrenia.Methods: Ten consenting patients with a confirmed Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision diagnosis of schizophrenia were identified. All patients failed at least one 12-week treatment trial with risperidone or olanzapine. Gabapentin was added to ongoing antipsychotic treatment with olanzapine or risperidone for eight weeks. The primary outcome measure was the Positive and Negative Syndrome Scale (PANSS. Other scales included the Calgary Depression Scale (CDSS and the Abnormal Involuntary Movement Scale (AIMS. Repeated-measures multivariate analysis of variance was utilized to examine changes in outcome measures over time with adjunctive treatment with gabapentin.Results: There was a significant drop in the PANSS and CDSS scores at endpoint (week 8. There were no significant differences between the two treatment groups with regard to changes in all outcome measures or in AIMS score. The adjunctive treatments were well tolerated and side effects were transient.Conclusion: Gabapentin could be used successfully as an adjunct to novel antipsychotics in partially responsive schizophrenia. However, large controlled studies are needed to examine the effectiveness of gabapentin in psychotic disorders.Keywords: schizophrenia, refractory, adjunctive treatment, gabapentin, risperidone, olanzapine

  17. Efficacy of olanzapine in symptom relief and quality of life in gastric cancer patients receiving chemotherapy

    Directory of Open Access Journals (Sweden)

    Novin Nikbakhsh

    2016-01-01

    Full Text Available Background: Considering the incidence and prevalence rates of gastric cancer in Mazandaran Province of Iran, this research was performed to evaluate the efficacy and safety of olanzapine in symptom relief and quality of life (QOL improvement of gastric patients receiving chemotherapy. Materials and Methods: This clinical trial was conducted on thirty new cases of gastric cancer patients whose treatment protocol was planned on chemotherapy and were allocated into two groups by simple random sampling. Intervention group (15 patients received olanzapine tablets (2.5–10 mg/day a day before the beginning of chemotherapy; in the 1st day of chemotherapy to 8 weeks after chemotherapy, besides the routine treatment regimens. The control group received only the routine treatment regimens. The patients were followed for 8 weeks after intervention. All of the patients were assessed with Hospital Anxiety and Depression Scale (HADS and WHO-QOL-BREF questionnaires; further, Rhodes index was used to evaluate nausea and vomiting (N/V status. Results: All the recruited patients continued the allocated interventions (no lost to follow-up. N/V decreased in the case group, but the difference was not statistically significant (P = 0.438. The patients' appetite and body mass index increased (P = 0.006. Anxiety and depression subscales of HADS had significant differences between the two groups (P 0.05. No significant increase was observed in fasting and 2-h postprandial blood glucose and lipid profile (P > 0.05. Conclusion: Olanzapine can be considered as an effective drug to increase appetite and decrease anxiety and depression in patients with gastric cancer.

  18. Single dose bioequivalence study of two brands of olanzapine 10 mg tablets in Iranian healthy volunteers.

    Science.gov (United States)

    Zakeri-Milani, P; Islambulchilar, Z; Ghanbarzadeh, S; Valizadeh, H

    2013-07-01

    This single dose, randomized, open label, 2-period and crossover study in healthy Iranian adult volunteers was conducted to compare the bioavailability of 2 branded formulations of olanzapine 10 mg tablets. 24 volunteers received one tablet of each olanzapine 10 mg formulation. Drugs were administered after a 12 h overnight fast in each of 2 treatment days which separated by a 2-week washout period. Serial blood samples were collected over a period of 72 h. Plasma was analyzed using a validated high performance liquid chromatography method with ultraviolet detection in the range of 2-24 ng/mL with a lower limit of quantitation of 1.25 ng/mL. A non-compartmental method was employed to determine the pharmacokinetic properties (Cmax, Tmax, AUC0-t, AUC0-∞ and T1/2) to test to bioequivalence. Cmax, AUC0-t and AUC0-∞ were used to test the bioequivalence after log-transformation of plasma data. The mean (SD) Cmax, AUC0-t and AUC0-∞ for the test formulation were 15.82 (3.15) ng/mL, 447.19 (100.64) ng.h/L and 570.75 (130.55) ng.h/L respectively. Corresponding values for the test formulation were 15.72 (4.25) ng/mL, 440.37 (98.75) ng.h/mL and 558.66 (129.57) ng.h/mL. For test formulation vs. the reference formulation, the 90% CIs of the least squares mean test/reference ratios of Cmax, AUC0-t and AUC0-∞ were 97.6-110.0%, 96.4-109.4% and 97.3-109.2%. In these volunteers, based on the FDA regulatory definition, results from the pharmacokinetic analysis suggested that the test and reference formulations of olanzapine 10 mg tablets were bioequivalent.

  19. Long-term treatment with olanzapine in hospital conditions: Prevalence and predictors of the metabolic syndrome

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    Popović Irena

    2015-01-01

    Full Text Available Introduction. The risk of metabolic abnormalities is greatly increased in schizophrenic patients started on an atypical antipsychotic medication. Patients with psychiatric disorders exceed mortality ranges resulting from, among others, increased risk of cardiovascular events. Other factors contributing to the development of metabolic syndrome include prolonged duration of illness, increasing age, female sex and lifestyle factors. Objective. This cross-sectional study was taken up to assess the prevalence of the metabolic syndrome (MetS in schizophrenic patients receiving olanzapine monotherapy for at least six months and to determine the most important risk factors associated with metabolic syndrome presence in these patients. Methods. A total of 93 long term hospitalized schizophrenic patients (71 men, 22 women, had a screening of the following: case-history data, psychiatric scales, anthropometric measures, blood (fasting glucose, lipid status, C-reactive protein - CRP and urine samples (microalbuminuria. Results. Prevalence of MetS according to International Diabetes Federation criteria in our study was 34.4%. The multivariate analysis distinguished the following significant predictors of MetS presence (in order of appearance: data about diabetes mellitus in family history (p=0.002, body mass index >25 kg/m2 (p=0.002, hyperlipidemia in family history (p=0.008, and elevated CRP value (p=0.042. Conclusion. High rate of MetS in patients treated with olanzapine in this study exceeds MetS prevalence in general population. Among observed parameters, our study pointed to several “high risk” predictors associated with MetS presence. Regular monitoring of cardiometabolic risk factors is highly recommended. Positive heredity distress mentioned above may direct a psychiatrist to prescribe some other drug than olanzapine in the long term treatment of schizophrenia.

  20. Combination therapy of inhaled steroids and long-acting beta2-agonists in asthma–COPD overlap syndrome

    Directory of Open Access Journals (Sweden)

    Lee SY

    2016-11-01

    Full Text Available Suh-Young Lee,1,* Hye Yun Park,2,* Eun Kyung Kim,3 Seong Yong Lim,4 Chin Kook Rhee,5 Yong Il Hwang,6 Yeon-Mok Oh,7 Sang Do Lee,7 Yong Bum Park1 On behalf of the KOLD Study Group 1Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, 2Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 3Department of Internal Medicine, Bundang CHA Medical Center, CHA University College of Medicine, Seongnam, 4Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 5Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 6Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Gyeonggido, 7Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Ulsan, Republic of Korea *These authors contributed equally to this work Background: The efficacy of inhaled corticosteroids (ICSs/long-acting beta2-agonist (LABA treatment in patients with asthma–chronic obstructive pulmonary disease (COPD overlap syndrome (ACOS compared to patients with COPD alone has rarely been examined. This study aimed to evaluate the clinical efficacy for the improvement of lung function after ICS/LABA treatment in patients with ACOS compared to COPD alone patients. Methods: Patients with stable COPD were selected from the Korean Obstructive Lung Disease (KOLD cohort. Subjects began a 3-month ICS/LABA treatment after a washout period. ACOS was defined when the patients had 1 a personal history of asthma, irrespective of age, and wheezing in the last 12 months in a self-reported survey

  1. Comparative efficacy of long-acting muscarinic antagonist monotherapies in COPD: a systematic review and network meta-analysis

    Directory of Open Access Journals (Sweden)

    Ismaila AS

    2015-11-01

    Full Text Available Afisi Segun Ismaila,1,2 Eline L Huisman,3 Yogesh Suresh Punekar,4 Andreas Karabis31Value Evidence and Outcomes, GlaxoSmithKline, Research Triangle Park, NC, USA; 2Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada; 3Real World Strategy and Analytics, Mapi Group, Houten, the Netherlands; 4Value Evidence and Outcomes, GlaxoSmithKline, Uxbridge, UKBackground: Randomized, controlled trials comparing long-acting muscarinic antagonist (LAMA efficacy in COPD are limited. This network meta-analysis (NMA assessed the relative efficacy of tiotropium 18 µg once-daily (OD and newer agents (aclidinium 400 µg twice-daily, glycopyrronium 50 µg OD, and umeclidinium 62.5 µg OD.Methods: A systematic literature review identified randomized, controlled trials of adult COPD patients receiving LAMAs. A NMA within a Bayesian framework examined change from baseline in trough forced expiratory volume in 1 second (FEV1, transitional dyspnea index focal score, St George’s Respiratory Questionnaire score, and rescue medication use.Results: Twenty-four studies (n=21,311 compared LAMAs with placebo/each other. Aclidinium, glycopyrronium, tiotropium, and umeclidinium, respectively, demonstrated favorable results versus placebo, for change from baseline (95% credible interval in 12-week trough FEV1 (primary endpoint: 101.40 mL [77.06–125.60]; 117.20 mL [104.50–129.90]; 114.10 mL [103.10–125.20]; 136.70 mL [104.20–169.20]; 24-week trough FEV1 (128.10 mL [84.10–172.00]; 135.80 mL [123.10–148.30]; 106.40 mL [95.45–117.30]; 115.00 mL [74.51–155.30]; 24-week St George’s Respiratory Questionnaire score (-4.60 [-6.76 to -2.54]; -3.14 [-3.83 to -2.45]; -2.43 [-2.92 to -1.93]; -4.69 [-7.05 to -2.31]; 24-week transitional dyspnea index score (1.00 [0.41–1.59]; 1.01 [0.79–1.22]; 0.82 [0.62–1.02]; 1.00 [0.49–1.51]; and 24-week rescue medication use (data not available; -0.41 puffs/day [-0.62 to -0.20]; -0.52 puffs/day [-0

  2. 'Myxoedema madness' with Capgras syndrome and catatonic features responsive to combination olanzapine and levothyroxine.

    Science.gov (United States)

    Shlykov, Maksim A; Rath, Swapnil; Badger, Alison; Winder, Gerald Scott

    2016-09-09

    We present the case of an elderly woman with hypothyroidism and no psychiatric history who presented with new onset of psychosis, paranoia, catatonic features and Capgras syndrome (CS). This case illustrates the spectrum of neuropsychiatric symptoms that may accompany hypothyroidism and the importance of considering thyroid dysfunction as a primary contributor to severe psychiatric symptoms, especially in previously stable patients. We demonstrate the effectiveness of combination levothyroxine and olanzapine, with its favourable cardiac profile, in the treatment of myxoedema madness. Antipsychotics can be weaned once psychiatric symptoms resolve and hormone levels are stabilised. 2016 BMJ Publishing Group Ltd.

  3. Use of Orally Disintegrating Olanzapine During Electroconvulsive Therapy for Prevention of Postictal Agitation.

    Science.gov (United States)

    Hermida, Adriana P; Janjua, A Umair; Tang, Yilang; Syre, Sharyn R; Job, Gregory; McDonald, William M

    2016-11-01

    A major medical problem for patients undergoing electroconvulsive therapy (ECT) is the occurrence of postictal agitation (PIA). This phenomenon is associated with confusion and disorientation that can have severe clinical implications for the safety of the patient and health care professionals. Many different pharmacological strategies have been used to prevent PIA. We present data on 40 patients who suffered from PIA after a course of ECT and evaluate the prophylactic use of orally disintegrating olanzapine in the prevention of PIA in subsequent ECT treatments.

  4. Management of symptoms associated with advanced cancer: olanzapine and mirtazapine. A World Health Organization project.

    Science.gov (United States)

    Davis, Mellar P; Khawam, Elias; Pozuelo, Leo; Lagman, Ruth

    2002-08-01

    Advanced cancer patients are polysymptomatic and often receive multiple medications for symptom relief. Common symptoms include anorexia, weight loss, delirium and depression. Olanzapine and mirtazapine may have several advantages over older agents despite increased acquisition costs. Both medications can treat several symptoms with a low risk for drug-drug interactions and with only once- or twice-daily dosing. Drug side effects are low, compared with more conventionally used agents. The pharmacokinetics and pharmacodynamics of both agents are unique and explain many of the benefits. More research and clinical experience will be necessary to define their role in the palliation of advanced cancer.

  5. Doripenem Injection

    Science.gov (United States)

    ... injection is in a class of medications called carbapenem antibiotics. It works by killing bacteria.Antibiotics such ... if you are allergic to doripenem injection; other carbapenem antibiotics such as imipenem/cilastatin (Primaxin) or meropenem ( ...

  6. Methotrexate Injection

    Science.gov (United States)

    Methotrexate injection is used alone or in combination with other medications to treat gestational trophoblastic tumors (a ... in bones) after surgery to remove the tumor. Methotrexate injection is also used to treat severe psoriasis ( ...

  7. Bendamustine Injection

    Science.gov (United States)

    Bendamustine injection is used to treat chronic lymphocytic leukemia (CLL; a type of cancer of the white ... injection. You should use birth control to prevent pregnancy in yourself or your partner during your treatment ...

  8. Caspofungin Injection

    Science.gov (United States)

    Caspofungin injection is used in adults and children 3 months of age and older to treat yeast ... people with a weakened ability to fight infection. Caspofungin injection is in a class of antifungal medications ...

  9. Temozolomide Injection

    Science.gov (United States)

    Temozolomide is used to treat certain types of brain tumors. Temozolomide is in a class of medications called alkylating ... Temozolomide injection comes as a powder to be added to fluid and injected over 90 minutes intravenously ( ...

  10. Pembrolizumab Injection

    Science.gov (United States)

    Pembrolizumab injection is used to treat melanoma (a type of skin cancer) that cannot be treated with ... who have a specific type of melanoma tumor. Pembrolizumab injection is also used to treat a certain ...

  11. Lacosamide Injection

    Science.gov (United States)

    ... injection is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in ... older (about 1 in 500 people) who took anticonvulsants like lacosamide injection to treat various conditions during ...

  12. Midazolam Injection

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    ... injection is in a class of medications called benzodiazepines. It works by slowing activity in the brain ... breast-feeding.talk to your doctor about the risks and benefits of receiving midazolam injection if you ...

  13. Doxycycline Injection

    Science.gov (United States)

    Doxycycline injection is used to treat or prevent bacterial infections, including pneumonia and other respiratory tract infections. ... certain skin, genital, intestine, and urinary system infections. Doxycycline injection may be used to treat or prevent ...

  14. Paclitaxel Injection

    Science.gov (United States)

    ... with other medications. Paclitaxel injection manufactured with polyoxyethylated castor oil is used to treat ovarian cancer (cancer that ... cancer, and lung cancer. Paclitaxel injection with polyoxyethylated castor oil is also used to treat Kaposi's sarcoma (a ...

  15. Etanercept Injection

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    ... will be using the prefilled syringe or automatic injection device, tell your doctor if you or the person who will be injecting the medication for you are allergic to rubber or latex.tell your doctor and pharmacist what ...

  16. Cyclosporine Injection

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    Cyclosporine injection is used with other medications to prevent transplant rejection (attack of the transplanted organ by ... who have received kidney, liver, and heart transplants. Cyclosporine injection should only be used to treat people ...

  17. Estrogen Injection

    Science.gov (United States)

    The estradiol cypionate and estradiol valerate forms of estrogen injection are used to treat hot flushes (hot ... should consider a different treatment. These forms of estrogen injection are also sometimes used to treat the ...

  18. Cefotaxime Injection

    Science.gov (United States)

    Cefotaxime injection is used to treat certain infections caused by bacteria including pneumonia and other lower respiratory ... skin, blood, bone, joint, and urinary tract infections. Cefotaxime injection may also be used before surgery, and ...

  19. Designing a Long Acting Erythropoietin by Fusing Three Carboxyl-Terminal Peptides of Human Chorionic Gonadotropin β Subunit to the N-Terminal and C-Terminal Coding Sequence

    Directory of Open Access Journals (Sweden)

    Fuad Fares

    2011-01-01

    Full Text Available A new analog of EPO was designed by fusing one and two CTPs to the N-terminal and C-terminal ends of EPO (EPO-(CTP3, respectively. This analog was expressed and secreted efficiently in CHO cells. The in vitro test shows that the activity of EPO-(CTP3 in TFI-1 cell proliferation assay is similar to that of EPO-WT and commercial rHEPO. However, in vivo studies indicated that treatment once a week with EPO-(CTP3 (15 μg/kg dramatically increased (~8 folds haematocrit as it was compared to rHuEPO. Moreover, it was found that EPO-(CTP3 is more effective than rHuEPO and Aranesp in increasing reticulocyte number in mice blood. The detected circulatory half-lives of rHuEPO, Aranesp, and EPO-(CTP3 following IV injection of 20 IU were 4.4, 10.8, and 13.1 h, respectively. These data established the rational for using this chimera as a long-acting EPO analog in clinics. The therapeutic efficacy of EPO-CTP analog needs to be established in higher animals and in human clinical trials.

  20. Ustekinumab Injection

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    ... Do not inject into an area where the skin is tender, bruised, red, or hard or where you have scars or stretch marks.Your doctor or pharmacist will ... injection.you should know that ustekinumab injection may decrease your ability ... new or changing skin lesions, minor infections (such as open cuts or ...

  1. Ranitidine Injection

    Science.gov (United States)

    Ranitidine injection comes as a solution (liquid) to be mixed with another fluid and injected intravenously (into a vein) over 5 to 20 minutes. Ranitidine may also be injected into a muscle. It is usually given every 6 to 8 hours, but may also be given ...

  2. An Accelerated Release Study to Evaluate Long-Acting Contraceptive Levonorgestrel-Containing in Situ Forming Depot Systems.

    Science.gov (United States)

    Janagam, Dileep R; Wang, Lizhu; Ananthula, Suryatheja; Johnson, James R; Lowe, Tao L

    2016-09-01

    Biodegradable polymer-based injectable in situ forming depot (ISD) systems that solidify in the body to form a solid or semisolid reservoir are becoming increasingly attractive as an injectable dosage form for sustained (months to years) parenteral drug delivery. Evaluation of long-term drug release from the ISD systems during the formulation development is laborious and costly. An accelerated release method that can effectively correlate the months to years of long-term release in a short time such as days or weeks is economically needed. However, no such accelerated ISD system release method has been reported in the literature to date. The objective of the current study was to develop a short-term accelerated in vitro release method for contraceptive levonorgestrel (LNG)-containing ISD systems to screen formulations for more than 3-month contraception after a single subcutaneous injection. The LNG-containing ISD formulations were prepared by using biodegradable poly(lactide-co-glycolide) and polylactic acid polymer and solvent mixtures containing N-methyl-2-pyrrolidone and benzyl benzoate or triethyl citrate. Drug release studies were performed under real-time (long-term) conditions (PBS, pH 7.4, 37 °C) and four accelerated (short-term) conditions: (A) PBS, pH 7.4, 50 °C; (B) 25% ethanol in PBS, pH 7.4, 50 °C; (C) 25% ethanol in PBS, 2% Tween 20, pH 7.4, 50 °C; and (D) 25% ethanol in PBS, 2% Tween 20, pH 9, 50 °C. The LNG release profile, including the release mechanism under the accelerated condition D within two weeks, correlated (r² ≥ 0.98) well with that under real-time conditions at four months.

  3. An Accelerated Release Study to Evaluate Long-Acting Contraceptive Levonorgestrel-Containing in Situ Forming Depot Systems

    Directory of Open Access Journals (Sweden)

    Dileep R. Janagam

    2016-09-01

    Full Text Available Biodegradable polymer-based injectable in situ forming depot (ISD systems that solidify in the body to form a solid or semisolid reservoir are becoming increasingly attractive as an injectable dosage form for sustained (months to years parenteral drug delivery. Evaluation of long-term drug release from the ISD systems during the formulation development is laborious and costly. An accelerated release method that can effectively correlate the months to years of long-term release in a short time such as days or weeks is economically needed. However, no such accelerated ISD system release method has been reported in the literature to date. The objective of the current study was to develop a short-term accelerated in vitro release method for contraceptive levonorgestrel (LNG-containing ISD systems to screen formulations for more than 3-month contraception after a single subcutaneous injection. The LNG-containing ISD formulations were prepared by using biodegradable poly(lactide-co-glycolide and polylactic acid polymer and solvent mixtures containing N-methyl-2-pyrrolidone and benzyl benzoate or triethyl citrate. Drug release studies were performed under real-time (long-term conditions (PBS, pH 7.4, 37 °C and four accelerated (short-term conditions: (A PBS, pH 7.4, 50 °C; (B 25% ethanol in PBS, pH 7.4, 50 °C; (C 25% ethanol in PBS, 2% Tween 20, pH 7.4, 50 °C; and (D 25% ethanol in PBS, 2% Tween 20, pH 9, 50 °C. The LNG release profile, including the release mechanism under the accelerated condition D within two weeks, correlated (r2 ≥ 0.98 well with that under real-time conditions at four months.

  4. An Accelerated Release Study to Evaluate Long-Acting Contraceptive Levonorgestrel-Containing in Situ Forming Depot Systems

    Science.gov (United States)

    Janagam, Dileep R.; Wang, Lizhu; Ananthula, Suryatheja; Johnson, James R.; Lowe, Tao L.

    2016-01-01

    Biodegradable polymer-based injectable in situ forming depot (ISD) systems that solidify in the body to form a solid or semisolid reservoir are becoming increasingly attractive as an injectable dosage form for sustained (months to years) parenteral drug delivery. Evaluation of long-term drug release from the ISD systems during the formulation development is laborious and costly. An accelerated release method that can effectively correlate the months to years of long-term release in a short time such as days or weeks is economically needed. However, no such accelerated ISD system release method has been reported in the literature to date. The objective of the current study was to develop a short-term accelerated in vitro release method for contraceptive levonorgestrel (LNG)-containing ISD systems to screen formulations for more than 3-month contraception after a single subcutaneous injection. The LNG-containing ISD formulations were prepared by using biodegradable poly(lactide-co-glycolide) and polylactic acid polymer and solvent mixtures containing N-methyl-2-pyrrolidone and benzyl benzoate or triethyl citrate. Drug release studies were performed under real-time (long-term) conditions (PBS, pH 7.4, 37 °C) and four accelerated (short-term) conditions: (A) PBS, pH 7.4, 50 °C; (B) 25% ethanol in PBS, pH 7.4, 50 °C; (C) 25% ethanol in PBS, 2% Tween 20, pH 7.4, 50 °C; and (D) 25% ethanol in PBS, 2% Tween 20, pH 9, 50 °C. The LNG release profile, including the release mechanism under the accelerated condition D within two weeks, correlated (r2 ≥ 0.98) well with that under real-time conditions at four months. PMID:27598191

  5. Simultaneous determination of olanzapine and fluoxetine hydrochloride in capsules by spectrophotometry, TLC-spectrodensitometry and HPLC.

    Science.gov (United States)

    Tantawy, Mahmoud A; Hassan, Nagiba Y; Elragehy, Nariman A; Abdelkawy, Mohamed

    2013-03-01

    This paper describes sensitive, accurate and precise spectrophotometric, TLC-spectrodensitometric and high performance liquid chromatographic (HPLC) methods for simultaneous determination of olanzapine and fluoxetine HCl. Two spectrophotometric methods were developed, namely; first derivative (D (1)) and derivative ratio (DD (1)) methods. The TLC method employed aluminum TLC plates precoated with silica gel GF254 as the stationary phase and methanol:toluene:ammonia (7:3:0.1, by volume) as the mobile phase, where the chromatogram was scanned at 235 nm. The developed HPLC method used a reversed phase C18 column with isocratic elution. The mobile phase composed of phosphate buffer pH 4.0:acetonitrile:triethylamine (53:47:0.03, by volume) at flow rate of 1.0 mL min(-1). Quantitation was achieved with UV detection at 235 nm. The methods were validated according to the International Conference on Harmonization (ICH) guidelines. The selectivity of the proposed methods was tested using laboratory-prepared mixtures. The developed methods were successfully applied for the determination of olanzapine and fluoxetine HCl in bulk powder and combined capsule dosage form.

  6. Olanzapine use in a manic patient during second and third trimester pregnancy

    Directory of Open Access Journals (Sweden)

    Choi L

    2014-02-01

    Full Text Available Lynn Choi, Soo-Hyun Joo, Jong-Hyun Jeong Department of Psychiatry, St Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea Abstract: Women with bipolar disorder have a high risk for symptom exacerbation during pregnancy and the risk is elevated further when mood stabilizers are discontinued. This report describes a 31-year-old bipolar woman who discontinued medication before pregnancy but had to resume her pharmacotherapy due to manic episodes that recurred during the second trimester. Olanzapine, an atypical antipsychotic, was administered from week 25 of gestation and then replaced with quetiapine in week 35 of gestation. Even though a consensus on clinical interventions for pregnant patients with symptom relapse has not been reached, clinicians should still discuss pregnancy and therapeutic management with every female bipolar patient of childbearing age. This discussion is important because treatment can be managed most effectively in these individuals if pregnancy is planned. Ultimately, clinical decisions should be made on a case-by-case basis, weighing the risks to the mother and fetus between the disorder itself and the teratogenicity of pharmacotherapy. Keywords: pregnancy, bipolar disorder, olanzapine, manic

  7. Olanzapine reduces physical activity in rats exposed to activity-based anorexia : possible implications for treatment of anorexia nervosa?

    NARCIS (Netherlands)

    Hillebrand, Jacquelien J G; van Elburg, Annemarie A; Kas, Martien J H; van Engeland, Herman; Adan, Roger A H

    2005-01-01

    BACKGROUND: Anorexia nervosa (AN) patients often show extreme hypophagia and excessive physical activity. Activity-based anorexia (ABA) is considered an animal model of AN and mimics food restriction and hyperactivity in rats. This study investigated whether treatment with olanzapine (Zyprexa) reduc

  8. Comparison of the effect of Olanzapine and Sertraline on patients suffering from personality disorder, receiving methadone maintenance therapy

    Directory of Open Access Journals (Sweden)

    mozhgan Jariani

    2009-03-01

    Full Text Available Background: Borderline Personality disorder is a disabling disease affecting 2% of general population. Various drugs have been suggested for treatment of borderline Personality disorder. If a drug could alleviate a wide range of symptoms, it would be more suitable. In these disorders drug addiction is very common. This fact makes the symptoms complicated and the treatment more difficult. This study is designed to evaluate the effect of Olanzapine and Sertraline in patients suffering from personality disorders who are on methadone maintenance therapy. Materials and Methods: This clinical trial study was carried out on 120 male and female cases chosen for methadone maintenance therapy through interview by a psychiatrist based on DSM-IV-TR diagnostic criteria for BPD. Afterwards they were randomly divided into two groups. These groups separately received Olanzapine (5-10 mg daily and Sertraline (50-100 mg daily therapy. The SCL-90 questionnaire was filled out by the participants before treatment and at the 4th, 8th and 12th weeks of the treatment. Results: According to this clinical trial, Olanzapine and Sertraline were effective in ameliorating symptoms of depression, anxiety and aggression, reducing sensitivity in interpersonal relationship and alleviating obsessive symptoms, pessimistic behaviors and somatization disorders in patients with personality disorders on methadone maintenance therapy. Conclusion: As results of this study stated that Olanzapine and Sertraline are definitely effective in alleviating symptoms of patients with personality disorder, prescribing theses drugs are highly recommended for these patients. .

  9. Mechanism-Based Pharmacokinetic-Pharmacodynamic Modeling of the Dopamine D-2 Receptor Occupancy of Olanzapine in Rats

    NARCIS (Netherlands)

    Johnson, Martin; Kozielska, Magdalena; Reddy, Venkatesh Pilla; Vermeulen, An; Li, Cheryl; Grimwood, Sarah; de Greef, Rik; Groothuis, Geny M. M.; Danhof, Meindert; Proost, Johannes H.

    2011-01-01

    A mechanism-based PK-PD model was developed to predict the time course of dopamine D-2 receptor occupancy (D2RO) in rat striatum following administration of olanzapine, an atypical antipsychotic drug. A population approach was utilized to quantify both the pharmacokinetics and pharmacodynamics of ol

  10. Translation of randomised controlled trial findings into clinical practice: comparison of olanzapine and valproate in the EMBLEM study

    DEFF Research Database (Denmark)

    Novick, D; Gonzalez-Pinto, A; Haro, J M

    2009-01-01

    OBJECTIVES: The aim of this study was to compare the outcomes of olanzapine- and valproate-treated patients in an observational study of acute mania with the results of a randomised controlled trial (RCT) assessing the same treatments. METHODS: EMBLEM (European Mania in Bipolar Evaluation...

  11. Subjective response to antipsychotic treatment and compliance in schizophrenia. A naturalistic study comparing olanzapine, risperidone and haloperidol (EFESO Study

    Directory of Open Access Journals (Sweden)

    Sacristán Jose A

    2001-12-01

    Full Text Available Abstract Background In order to compare the effectiveness of different antipsychotic drugs in the treatment of schizophrenia it is very important to evaluate subjective response and compliance in patient cohorts treated according to routine clinical practice. Method Outpatients with schizophrenia entered this prospective, naturalistic study when they received a new prescription for an antipsychotic drug. Treatment assignment was based on purely clinical criteria, as the study did not include any experimental intervention. Patients treated with olanzapine, risperidone or haloperidol were included in the analysis. Subjective response was measured using the 10-item version of the Drug Attitude Inventory (DAI-10, and treatment compliance was measured using a physician-rated 4 point categorical scale. Results A total of 2128 patients initiated treatment (as monotherapy with olanzapine, 417 with risperidone, and 112 with haloperidol. Olanzapine-treated patients had significantly higher DAI-10 scores and significantly better treatment compliance compared to both risperidone- and haloperidol-treated patients. Risperidone-treated patients had a significantly higher DAI-10 score compared to haloperidol-treated patients. Conclusion Subjective response and compliance were superior in olanzapine-treated patients, compared to patients treated with risperidone and haloperidol, in routine clinical practice. Differences in subjective response were explained largely, but not completely, by differences in incidence of EPS.

  12. Determination of olanzapine in whole blood using simple protein precipitation and liquid chromatography-tandem mass spectrometry

    DEFF Research Database (Denmark)

    Nielsen, Marie Katrine Klose; Johansen, Sys Stybe

    2009-01-01

    A simple, sensitive, and reproducible liquid chromatography-tandem mass spectrometry method has been developed and validated for the quantification of the antipsychotic drug olanzapine in whole blood using dibenzepine as internal standard (IS). After acidic methanol-induced protein precipitation...

  13. Olanzapine reduces physical activity in rats exposed to activity-based anorexia : possible implications for treatment of anorexia nervosa?

    NARCIS (Netherlands)

    Hillebrand, Jacquelien J G; van Elburg, Annemarie A; Kas, Martien J H; van Engeland, Herman; Adan, Roger A H

    2005-01-01

    BACKGROUND: Anorexia nervosa (AN) patients often show extreme hypophagia and excessive physical activity. Activity-based anorexia (ABA) is considered an animal model of AN and mimics food restriction and hyperactivity in rats. This study investigated whether treatment with olanzapine (Zyprexa) reduc

  14. Mucoadhesive Amphiphilic Methacrylic Copolymer-Functionalized Poly(ε-caprolactone) Nanocapsules for Nose-to-Brain Delivery of Olanzapine.

    Science.gov (United States)

    Fonseca, Francisco N; Betti, Andresa H; Carvalho, Flávia C; Gremião, Maria P D; Dimer, Frantiescoli A; Guterres, Sílvia S; Tebaldi, Marli L; Rates, Stela M K; Pohlmann, Adriana R

    2015-08-01

    Nose-to-brain drug delivery has been proposed to overcome the low absorption of drugs in central nervous system due to the absence of brain-blood barrier in the olfactory nerve pathway. However, the presence of a mucus layer and quick clearance limit the use of this route. Herein, amphiphilic methacrylic copolymer-functionalized poly(ε-caprolactone) nanocapsules were proposed as a mucoadhesive system to deliver olanzapine after intranasal administration. In vitro evaluations showed that these nanocapsules were able to interact with mucin (up to 17% of increment in particle size and 30% of reduction of particle concentration) and nasal mucosa (2-fold higher force for detaching), as well as to increase the retention of olanzapine (about 40%) on the nasal mucosa after continuous wash. The olanzapine-loaded amphiphilic methacrylic copolymer-functionalized PCL nanocapsules enhanced the amount of drug in the brain of rats (1.5-fold higher compared to the drug solution). In accordance with this finding, this formulation improved the prepulse inhibition impairment induced by apomorphine, which is considered as an operational measure of pre-attentive sensorimotor gating impairment present in schizophrenia. Besides, nanoencapsulated olanzapine did not affect the nasal mucosa integrity after repeated doses. These data evidenced that the designed nanocapsules are a promising mucoadhesive system for nose-to-brain delivery of drugs.

  15. A case of catatonia status-post left middle cerebral artery cerebrovascular accident, treated successfully with olanzapine.

    Science.gov (United States)

    Spiegel, David R; Klaiber, Nicholas

    2013-01-01

    Catatonia is a psychomotor phenomenon associated with psychiatric/medical conditions. We present a patient who developed catatonia status-post left middle cerebral artery infarct. With a Bush Francis Catatonia Rating Scale score of 43 on admission, treatment with olanzapine reduced this score to 2, by discharge.

  16. Heart rate variability in schizophrenic patients switched from typical antipsychotic agents to amisulpride and olanzapine. 3-month follow-up.

    Science.gov (United States)

    Wang, Ying-Chieh; Yang, Cheryl C H; Bai, Ya-Mei; Kuo, Terry B J

    2008-01-01

    Schizophrenia is a severe mental disorder that requires lifelong treatment, and therefore information on the cardiovascular safety and tolerance of antipsychotics is of significant clinical importance. Atypical antipsychotics have been used to treat schizophrenia patients since the 1990s, and more and more patients have been switched to these from typical antipsychotics; however, there is still no accessible evaluation tool for assessing cardiovascular safety. In this study, we used a computer-assisted 5-min measurement of resting heart rate variability (HRV) in schizophrenia patients who were switched to atypical antipsychotic agents (amisulpride and olanzapine) due to severe side effects (tardive dyskinesia). In 15 patients who switched to amisulpride and 18 to olanzapine, HRV was evaluated before the medication was switched, and patients were followed up every month for 3 months after the switch. Frequency-domain analyses of short-term and stationary respiratory rate (RR) intervals were performed to evaluate low-frequency power (LF; 0.04-0.15 Hz), high-frequency power (HF; 0.15-0.40 Hz), the ratio of LF to HF (LF/HF), and LF in normalized units (LF%). Our results showed significant increases in the mean, variance and HF of RR intervals in the amisulpride group, but not in the olanzapine group. These results indicate that amisulpride has a more vagotonic effect, suggesting greater cardiovascular safety as compared with olanzapine when subjects are switched from typical antipsychotic agents.

  17. Sertindole, in contrast to clozapine and olanzapine, does not disrupt water maze performance after acute or chronic treatment

    DEFF Research Database (Denmark)

    Didriksen, Michael; Kreilgaard, Mads; Arnt, Jørn

    2006-01-01

    Cognitive deficits in schizophrenia are associated with poor functional outcome, and may be further aggravated by treatment with antipsychotics. In the present study the acute and chronic (3 weeks of treatment) effects of clozapine, olanzapine, and sertindole on performance in the Morris water ma...

  18. Validation of a cage implant system for assessing in vivo performance of long-acting release microspheres.

    Science.gov (United States)

    Doty, Amy C; Hirota, Keiji; Olsen, Karl F; Sakamoto, Naoya; Ackermann, Rose; Feng, Meihua R; Wang, Yan; Choi, Stephanie; Qu, Wen; Schwendeman, Anna; Schwendeman, Steven P

    2016-12-01

    Here we describe development of a silicone rubber/stainless steel mesh cage implant system, much like that used to assess biocompatibility of biomaterials [1], for easy removal of injectable polymer microspheres in vivo. The sterile cage has a type 316 stainless steel mesh size (38 μm) large enough for cell penetration and free fluid flow in vivo but small enough for microsphere retention, and a silicone rubber shell for injection of the microspheres. Two model drugs, the poorly soluble steroid, triamcinolone acetonide, and the highly water-soluble luteinizing hormone-releasing hormone (LHRH) peptide superagonist, leuprolide, were encapsulated in PLGA microspheres large enough (63-90 μm) to be restrained by the cage implant in vivo. The in vitro release from both formulations was followed by ultra-performance liquid chromatography (UPLC) with and without the cage in a standard release media, PBS pH 7.4 + 0.02% Tween 80 + 0.05% sodium azide, at 37 °C. Pharmacokinetics (PK) in rats was assessed after SC injection or SC in-cage implantation of microspheres with plasma analysis by LC-MS/MS or EIA. Tr-A and leuprolide in vitro release was largely unaffected after the initial burst irrespective of the cage or test tube incubation vessel and release was much slower than observed in vivo for both drugs. Moreover, Tr-A and leuprolide pharmacokinetics with and without the cage were highly similar during the 2-3 week release duration before a significant inflammatory response was caused by the cage implant. Hence, the PK-validated cage implant provides a simple means to recover and evaluate the microsphere drug carriers in vivo during a time window of at least a few weeks in order to characterize the polymer microsphere release and erosion behavior in vivo. This approach may facilitate development of mechanism-based in vitro/in vivo correlations and enable development of more accurate and useful in vitro release tests. Copyright © 2016 Elsevier Ltd. All

  19. Risk of cardiovascular events after initiation of long-acting bronchodilators in patients with chronic obstructive lung disease: A population-based study

    Directory of Open Access Journals (Sweden)

    Almotasembellah Aljaafareh

    2016-09-01

    Full Text Available Objectives: Long-acting bronchodilators are mainstay treatment for moderate to severe chronic obstructive pulmonary disease. A growing body of evidence indicates an increased risk of cardiovascular events upon initiation of these medications. We hypothesize that this risk is higher in patients with chronic obstructive pulmonary disease who had a preexisting cardiovascular disease regardless of receipt of any cardiovascular medication. Methods: A retrospective cohort of patients with a diagnosis of chronic obstructive pulmonary disease based on two outpatient visits or one inpatient visit for chronic obstructive pulmonary disease (International Classification of Diseases, 9th Edition, Clinical Modification codes 491.x, 492.x, 496 in any year between 2001 and 2012 from a commercial insurance database. We then selected those initiating long-acting bronchodilator treatments between April 2001 and September 2012. Each patient had a 1 year look back period to determine history of cardiovascular disease or cardiovascular disease treatment from the time of first prescription of long-acting beta agonist, long-acting muscarinic antagonist, or long-acting beta agonist combined with inhaled corticosteroids. Patients were followed for 90 days for hospitalizations or emergency department visits for cardiovascular event. The cohort was divided into four groups based on the presence of cardiovascular disease (including ischemic heart disease, hypertension, ischemic stroke, heart failure, tachyarrhythmias and artery disease based on International Classification of Diseases, 9th Edition, Clinical Modification codes and cardiovascular disease treatment defined as acetylsalicylic acid, beta blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antiplatelet, anticoagulants, calcium channel blockers, nitrate, digoxin, diuretics, antiarrhythmics or statins. Odds of emergency department visit or hospitalization in the 90 days after

  20. GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells

    Science.gov (United States)

    Filatova, Elena; Kasian, Anastasiya; Kolomin, Timur; Rybalkina, Ekaterina; Alieva, Anelya; Andreeva, Lyudmila; Limborska, Svetlana; Myasoedov, Nikolay; Pavlova, Galina; Slominsky, Petr; Shadrina, Maria

    2017-01-01

    Clinical studies have shown that Selank had an anxiolytic effect comparable to that of classical benzodiazepine drugs, which can enhance the inhibitory effect of GABA by allosteric modulation of GABAA receptors. These data suggest that the molecular mechanism of the effect of Selank may also be related to its ability to affect the performance of the GABAergic system. To test this hypothesis, we studied the changes in expression of 84 genes involved in the functioning of the GABAergic system and in the processes of neurotransmission in the culture of neuroblastoma IMR-32 cells using qPCR method. As test substances, in addition to Selank, we selected the major GABAA receptor ligand, GABA, the atypical antipsychotic, olanzapine, and combinations of these compounds (Selank and GABA; Selank and olanzapine). We found no changes in the mRNA levels of the genes studied under the effect of Selank. The combined effect of GABA and Selank led to nearly complete suppression of changes in expression of genes in which mRNA levels changed under the effect of GABA. When Selank was used in conjunction with olanzapine, the expression alterations of more genes were observed compared with olanzapine alone. The data obtained indicate that Selank has no direct effect on the mRNA levels of the GABAergic system genes in neuroblastoma IMR-32 cells. At the same time, our results partially confirm the hypothesis that the peptide may affect the interaction of GABA with GABAA receptors. Our data also suggest that Selank may enhance the effect of olanzapine on the expression of the genes studied. PMID:28293190

  1. Natural oils as skin permeation enhancers for transdermal delivery of olanzapine: in vitro and in vivo evaluation.

    Science.gov (United States)

    Aggarwal, Geeta; Dhawan, Sanju; HariKumar, S L

    2012-03-01

    The feasibility of development of transdermal delivery system of olanzapine utilizing natural oils as permeation enhancers was investigated. Penetration enhancing potential of corn (maize) oil, groundnut oil and jojoba oil on in vitro permeation of olanzapine across rat skin was studied. The magnitude of flux enhancement factor with corn oil, groundnut oil and jojoba oil was 7.06, 5.31 and 1.9 respectively at 5mg/ml concentration in solvent system. On the basis of in vitro permeation studies, eudragit based matrix type transdermal patches of olanzapine were fabricated using optimized concentrations of natural oils as permeation enhancers. All transdermal patches were found to be uniform with respect to physical characteristics. The interaction studies carried out by comparing the results of ultraviolet, HPLC and FTIR analyses for the pure drug, polymers and mixture of drug and polymers indicated no chemical interaction between the drug and excipients. Corn oil containing unsaturated fatty acids was found to be promising natural permeation enhancer for transdermal delivery of olanzapine with greatest cumulative amount of drug permeated (1010.68 μg/cm²/h) up to 24 h and caused no skin irritation. The fabricated transdermal patches were found to be stable. The pharmacokinetic characteristics of the final optimized matrix patch (T2) were determined after transdermal application to rabbits. The calculated relative bioavailability of TDDS was 113.6 % as compared to oral administration of olanzapine. The therapeutic effectiveness of optimized transdermal system was confirmed by tranquillizing activity in rotarod and grip mice model.

  2. Effects of lactational exposure of olanzapine and risperidone on hematology and lymphoid organs histopathology: a comparative study in mice neonates.

    Science.gov (United States)

    Mishra, Akash C; Mohanty, Banalata

    2010-05-25

    Body weight gain, sexual/reproductive dysfunction and hematological abnormalities are serious consequences of atypical antipsychotics treatment. No attempts however have been made preclinically to elucidate the adverse hematological impacts. Presently, effects of lactational exposure of olanzapine (4, 8 and 10 mg/kg) and risperidone (1 and 2 mg/kg) on hematology as well as lymphoid organ histopathology of mice neonates were investigated. Both olanzapine and risperidone transfers through milk and make the neonates susceptible to their adverse side effects. Corticosterone elevation tendency of both the drugs further enhance the susceptibility for immune dysfunction. Analysis of total and differential leukocytes counts revealed neutropenia with all the doses of olanzapine but only with risperidone 2mg/kg. Weight analysis and histopathology of thymus and spleen indicated a state of suppression; less in the risperidone-exposed groups. Significant plasma corticosterone elevation occurred on 4 and 8 mg/kg olanzapine exposures but not with 10 mg/kg as well as with both the risperidone doses. Elevation of plasma prolactin levels occurred dose-dependently for both the drugs. Hematological toxicity (neutropenia) might be the direct toxic effects of the drugs/unstable metabolites on circulating neutrophils and/or on the bone marrow hemopoietic cells. Direct toxicity of the drugs might also have suppressed the lymphoid organs thymus and spleen. Further, it could be associated to hormonal imbalance induced by adverse pharmacological effects of the drugs on the endocrine system. Suppression of lymphoid organs in olanzapine groups might have resulted because of corticosteronemia and hyperprolactinemia, while in risperidone it could be mediated by pronounced hyperprolactinemic effect alone.

  3. Dulaglutide, a long-acting GLP-1 analog fused with an Fc antibody fragment for the potential treatment of type 2 diabetes

    DEFF Research Database (Denmark)

    Jimenez-Solem, Espen; Rasmussen, Mette H; Christensen, Mikkel

    2010-01-01

    Dulaglutide (LY-2189265) is a novel, long-acting glucagon-like peptide 1 (GLP-1) analog being developed by Eli Lilly for the treatment of type 2 diabetes mellitus (T2DM). Dulaglutide consists of GLP-1(7-37) covalently linked to an Fc fragment of human IgG4, thereby protecting the GLP-1 moiety from...... effects on HbA1c and body weight. If dulaglutide possesses similar efficacy to other GLP-1 analogs, the once-weekly treatment will most likely be welcomed by patients with T2DM....

  4. Subcutaneous Injections

    DEFF Research Database (Denmark)

    Thomsen, Maria

    This thesis is about visualization and characterization of the tissue-device interaction during subcutaneous injection. The tissue pressure build-up during subcutaneous injections was measured in humans. The insulin pen FlexTouchr (Novo Nordisk A/S) was used for the measurements and the pressure...... build-up was evaluated indirectly from the changes in the flow rate between subcutaneous injections and air injections. This method enabled the tissue counter pressure to be evaluated without a formal clinical study approval. The measurements were coupled to a model for the pressure evolution...

  5. In vivo pharmacological evaluations of novel olanzapine analogues in rats: a potential new avenue for the treatment of schizophrenia.

    Science.gov (United States)

    Jafari, Somayeh; Huang, Xu-Feng; Andrews, Jessica L; Fernandez-Enright, Francesca

    2013-01-01

    Olanzapine (Olz) is one of the most effective antipsychotic drugs commonly used for treating schizophrenia. Unfortunately, Olz administration is associated with severe weight gain and metabolic disturbances. Both patients and clinicians are highly interested in the development of new antipsychotics which are as effective as atypical antipsychotics but which have a lower propensity to induce metabolic side effects. In the present study, we examined two new derivatives of Olz; OlzEt (2-ethyl-4-(4'-methylpiperazin-1'-yl)-10Hbenzo[b]thieno[2,3-e][1,4]diazepine), and OlzHomo (2-ethyl-4-(4'-methyl-1',4'-diazepan-1'-yl)-10H-benzo[b]thieno[2,3-e] [1,4]diazepine), for their tendency to induce weight gain in rats. Weight gain and metabolic changes were measured in female Sprague Dawley rats. Animals were treated orally with Olz, OlzEt, OlzHomo (3 or 6 mg/kg/day), or vehicle (n = 8), three times daily at eight-hour intervals for 5 weeks. Furthermore, a phencyclidine (PCP)-treated rat model was used to examine the prevention of PCP-induced hyperlocomotor activity relevant for schizophrenia therapy. Male Sprague Dawley rats were pre-treated with a single dose (3 mg/kg/day) of Olz, OlzEt, OlzHomo, or vehicle (n = 12), for 2 weeks. Locomotor activity was recorded following a subcutaneous injection with either saline or PCP (10 mg/kg). Olz was found to induce weight gain, hyperphagia, visceral fat accumulation, and metabolic changes associated with reduced histamatergic H1 receptor density in the hypothalamus of treated rats. In contrast, OlzEt and OlzHomo presented promising antipsychotic effects, which did not induce weight gain or fat deposition in the treated animals. Behavioural analysis showed OlzEt to attenuate PCP-induced hyperactivity to a level similar to that of Olz; however, OlzHomo showed a lower propensity to inhibit these stereotyped behaviours. Our data suggest that the therapeutic effectiveness of OlzHomo may be delivered at a higher dose than that of Olz

  6. Effects of olanzapine and betahistine co-treatment on serotonin transporter, 5-HT2A and dopamine D2 receptor binding density.

    Science.gov (United States)

    Lian, Jiamei; Huang, Xu-Feng; Pai, Nagesh; Deng, Chao

    2013-12-02

    Olanzapine is widely used in treating multiple domains of schizophrenia symptoms but induces serious metabolic side-effects. Recent evidence has showed that co-treatment of betahistine (a histaminergic H1 receptor agonist and H3 receptor antagonist) is effective for preventing olanzapine-induced weight gain/obesity, however it is not clear whether this co-treatment affects on the primary therapeutic receptor binding sites of olanzapine such as serotonergic 5-HT2A receptors (5-HT2AR) and dopaminergic D2 receptors (D2R). Therefore, this study investigated the effects of this co-treatment on 5-HT2AR, 5-HT transporter (5-HTT) and D2R bindings in various brain regions involved in antipsychotic efficacy. Female Sprague Dawley rats were administered orally (t.i.d.) with either olanzapine (1mg/kg), betahistine (2.7 mg/kg), olanzapine plus betahistine (O+B), or vehicle (control) for 2 weeks. Quantitative autoradiography was used to detect the density of [(3)H]ketanserin, [(3)H]paroxetine and [(3)H]raclopride binding site to 5-HT2AR, 5-HTT and D2R. Compared to the controls, olanzapine significantly decreased [(3)H]ketanserin bindings to 5-HT2AR in the prefrontal cortex, cingulate cortex, and nucleus accumbens. Similar changes in 5-HT2AR bindings in these nuclei were also observed in the O+B co-treatment group. Olanzapine also significantly decreased [(3)H]paroxetine binding to 5-HTT in the ventral tegmental area and substantia nigra, however, both olanzapine only and O+B co-treatment did not affect [(3)H]raclopride binding to D2R. The results confirmed the important role of 5-HT2AR in the efficacy of olanzapine, which is not influenced by the O+B co-treatment. Therefore, betahistine co-treatment would be an effective combination therapy to reduce olanzapine-induced weight gain side-effects without affecting olanzapine's actions on 5-HT2AR transmissions.

  7. Evaluation of proximal therapeutic effect and distal social function restoration of olanzapine on schizophrenia patients%奥氮平对精神分裂症患者近期疗效及远期社会功能恢复效果评价

    Institute of Scientific and Technical Information of China (English)

    王长虹; 赵峥; 李晏; 潘苗; 刘旭

    2002-01-01

    Objective To evaluate the efficacy and prognosis of olanzapine in treatment of the schizophrenia. Methods A randomized controlled clinical study was performed to compare the efficacy and prognosis of olanzapine to that of chlorpromazine. 60 patients with schizophrenia were divided two groups. 32cases were treated with olanzapine. 28 cases were treated with chlorpromazine .Results The significant effect rate and effective rate on olanzapine group were 63% and 82% respectively ; which in chlorpromazine group were 32% and 50% .There were less side effects, and less recurrent rate in olanzapine. Conclusion Olanzapine is one of the safe and effective atypical antipsychotic for schizophrenia with significantly fewer side effects.

  8. Olanzapine promotes fat accumulation in male rats by decreasing physical activity, repartitioning energy and increasing adipose tissue lipogenesis while impairing lipolysis

    OpenAIRE

    Albaugh, Vance L.; Judson, Jessica G.; She, Pengxiang; Lang, Charles H.; Maresca, Kevin P.; Joyal, John L.; Christopher J Lynch

    2010-01-01

    Olanzapine and other atypical antipsychotics cause metabolic side effects leading to obesity and diabetes; while these continue to be an important public health concern, their underlying mechanisms remain elusive. Therefore, an animal model of these side effects was developed in male Sprague-Dawley rats. Chronic administration of olanzapine elevated fasting glucose, impaired glucose and insulin tolerance, increased fat mass but, in contrast to female rats, did not increase body weight or food...

  9. Olanzapine approved for the acute treatment of schizophrenia or manic/mixed episodes associated with bipolar I disorder in adolescent patients

    Directory of Open Access Journals (Sweden)

    Ann E Maloney

    2010-11-01

    Full Text Available Ann E Maloney1,2, Linmarie Sikich31Maine Medical Center Research Institute, Scarborough, ME, USA; 2Department of Psychiatry, Tufts University School of Medicine, Boston, MA, USA; 3Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USABackground: Severe and persistent mental illnesses in children and adolescents, such as early-onset schizophrenia spectrum (EOSS disorders and pediatric bipolar disorder (pedBP, are increasingly recognized. Few treatments have demonstrated efficacy in rigorous clinical trials. Enduring response to current medications appears limited. Recently, olanzapine was approved for the treatment of adolescents with schizophrenia or acute manic/mixed episodes in pedBP.Methods: PubMed searches were conducted for olanzapine combined with pharmacology, schizophrenia, or bipolar disorder. Searches related to schizophrenia and bipolar disorder were limited to children and adolescents. The bibliographies of the retrieved articles were hand-checked for additional relevant studies. The epidemiology, phenomenology, and treatment of EOSS and pedBP, and olanzapine’s pharmacology are reviewed. Studies of olanzapine treatment in youth with EOSS and pedBP are examined.Results: Olanzapine is efficacious for EOSS and pedBP. However, olanzapine is not more efficacious than risperidone, molindone, or haloperidol in EOSS and is less efficacious than clozapine in treatment-resistant EOSS. No comparative trials have been done in pedBP. Olanzapine is associated with weight gain, dyslipidemia, and transaminase elevations in youth. Extrapyramidal symptoms, neuroleptic malignant syndrome, and blood dyscrasias have also been reported but appear rare.Conclusions: The authors conclude that olanzapine should be considered a second-line agent in EOSS and pedBP due to its risks for significant weight gain and lipid dysregulation. Awareness of the consistent weight and metabolic changes observed in olanzapine

  10. [The efficiency of combinations of Enalapril and long-acting Nifedipin and Moxonidine in patients with arterial hypertension and a metabolic syndrome].

    Science.gov (United States)

    Mananko, E I; Vorob'eva, E V; Kalashnikova, T P; Bushkova, E A; Krasnova, N M; Idrisova, E M; Vengerovskiĭ, A I; Karpov, R S; Gruzdeva, O V; Kremenko, S V

    2008-01-01

    The aim of the study was to obtain a comparative evaluation of antihypertensive efficacy, tolerability and influence of combine therapy on myocardium mass, diastolic function of a left ventricle, lipid and carbohydrate exchange in patients with arterial hypertension in metabolic syndrome. Out of 40 examined cases 20 patients took enalapril and long-acting nifedipin and 20 ones--enalapril and moxonidine. All examination were been performed before administration of drugs and 6 months after the therapy. The dynamics of indices of ambulatory blood pressure monitoring, echocardiography, cycle ergometry, anthropometry, lipid, carbohydrate exchange and tolerability of conducted therapy was been evaluated. The use of this combination of the drugs may be recommended to be included in the treatment of arterial hypertension within the bounds of metabolic syndrome, as in most of cases they promote an achievement of target blood pressure level, have a cardioprotective action, high tolerability and favorable metabolic profile. The combination of enalapril and long-acting nifedipin has a more evident antihypertensive activity but a therapy with enalapril and moxonidine has a positive effect on the indices of carbohydrate exchange.

  11. Pituitary apoplexy causing spontaneous remission of acromegaly following long-acting octreotide therapy: a rare drug side effect or just a coincidence

    Science.gov (United States)

    Kumar, Sunil; Sharma, Shruti

    2016-01-01

    Pituitary apoplexy is characterized by abrupt onset of haemorrhage or non-haemorrhagic infarction of a pituitary adenoma. The clinical features include acute onset severe headache, visual field defects, meningeal irritation, ophthalmoplegia and hypopituitarism. The pituitary apoplexy may be clinically silent in ∼25% of patients. We report a case of acromegaly due to pituitary macroadenoma. The patient was started on long-acting octreotide therapy. On 3-month follow-up, the patient showed clinical and biochemical remission and the magnetic resonance imaging (MRI) of the brain showed subclinical haemorrhage and resolution of tumour. The octreotide therapy was stopped. On 6-month follow-up, the patient was still in remission and the MRI of brain revealed non-enhancing mixed intensities haemorrhagic and cystic areas of the pituitary gland. In our patient, whether spontaneous remission of acromegaly due to subclinical pituitary haemorrhage was coincidental or due to long-acting octreotide therapy is still a dilemma. We report this case because of rarity and clinical importance of this unusual occurrence. PMID:27123308

  12. Meaning-making matters in product design: users' sensory perceptions and experience evaluations of long-acting vaginal gels and intravaginal rings.

    Science.gov (United States)

    Rosen, Rochelle K; van den Berg, Jacob J; Vargas, Sara E; Senocak, Natali; Shaw, Julia G; Buckheit, Robert W; Smith, Kelley Alison; Guthrie, Kate Morrow

    2015-12-01

    Users' sensory perceptions and experiences of intravaginal products can inform acceptability and adherence. Focusing on the meanings women derive from formulation/device characteristics facilitates developers' design iterations toward optimizing user experience. We investigated how users of long-acting gels and intravaginal rings (IVRs) impute meaning to characteristics that may affect future product use. Focus groups were conducted with contraceptive IVR and vaginal lubricant users. Current perceptibility science and historical theory on the cultural acceptability of fertility regulating methods informed the analysis. A total of 21 IVR users and 29 lubricant users attended focus groups in which they manipulated products in their hands and discussed reactions to product characteristics. Participants used prior product experiences and sensory perceptions of prototype manipulations to inform meanings about product properties and performance for pregnancy, disease prevention, comfort, and perceived efficacy. The meanings derived from product characteristics depended on why the product would be used; a characteristic deemed problematic in one risk context may be considered preferable in another. Intravaginal product users create narratives that ascribe influence or causality to product characteristics. These meanings, whether correct or incorrect biologically, will shape vaginal product acceptability, use, and effectiveness. Long-acting and sustained-release drug delivery systems will be part of the multipurpose prevention continuum. Developers must consider how sensory experiences and culturally salient assumptions shape the meanings users make of product design characteristics. Those meanings will ultimately impact use and effectiveness. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Injection MD

    CERN Document Server

    Bartmann, W; Bracco, C; Drosdal, L; Gianfelice, E; Goddard, B; Kain, V; Papaphilippou, Y; Vanbavinckhove, G

    2012-01-01

    This note summarizes the results obtained at injection during the 2nd MD block and the floating MD block in July. Highlights are presented for injection in the LHC with the Q20 SPS optics, influence of the supercycle and injection with 25 ns bunch spacing. Beams were successfully injected into the LHC using the Q20 optics [1, 3]. Small corrections were needed to steer the beam in the transfer lines. Dispersion measurements were conducted for both beams. The horizontal normalized dispersion in TI2 was a factor 2 smaller for Q20 with respect to Q26, for TI8 on the other hand the opposite was observed. The results for injection loss dependency on super cycle composition show only a small increase in losses for beam 2. The losses observed must therefore mainly come from other sources such as shot-by-shot stability or quality of scraping. For the injection with 25 ns bunch spacing bunches were injected for both beams. For B1 up to the maximum of 288 bunches. For B2 on the other only up to 144 bunches were injected...

  14. Subcutaneous Injections

    DEFF Research Database (Denmark)

    Thomsen, Maria

    This thesis is about visualization and characterization of the tissue-device interaction during subcutaneous injection. The tissue pressure build-up during subcutaneous injections was measured in humans. The insulin pen FlexTouchr (Novo Nordisk A/S) was used for the measurements and the pressure...... build-up was evaluated indirectly from the changes in the flow rate between subcutaneous injections and air injections. This method enabled the tissue counter pressure to be evaluated without a formal clinical study approval. The measurements were coupled to a model for the pressure evolution...... in subcutaneous tissue, based on mass conservation and flow in a porous medium. From the measurements the flow permeability and bulk modulus of the tissue were determined. In the adipose tissue the drug forms a bolus from where it is absorbed by the blood capillaries. The spatial distribution of the injected...

  15. Zatosetron, a potent, selective, and long-acting 5HT3 receptor antagonist: synthesis and structure-activity relationships.

    Science.gov (United States)

    Robertson, D W; Lacefield, W B; Bloomquist, W; Pfeifer, W; Simon, R L; Cohen, M L

    1992-01-24

    Antagonists of 5HT3 receptors are clinically effective in treating nausea and emesis associated with certain oncolytic drugs, including cisplatin. Moreover, these agents may be useful in pharmacological management of several central nervous system disorders, including anxiety, schizophrenia, dementia, and substance abuse. Our studies on aroyltropanamides led to the discovery that dihydrobenzofuranyl esters and amides are potent 5HT3 receptor antagonists. Simple benzoyl derivatives of tropine and 3 alpha-aminotropane possessed weak 5HT3 receptor antagonist activity, as judged by blockade of bradycardia produced by iv injection of serotonin (5HT) to anesthetized rats. Within this series, use of benzofuran-7-carboxamide as the aroyl moiety led to a substantial increase of 5HT3 receptor affinity. The optimal 5HT3 receptor antagonist identified via extensive SAR studies was endo-5-chloro-2,3-dihydro-2,2-dimethyl-N-(8-methyl-8-azabicyclo[3.2.1]oc t- 3-yl)-7-benzofurancarboxamide (Z)-2-butenedioate (zatosetron maleate). The 7-carbamyl regiochemistry, dimethyl substitution, chloro substituent, and endo stereochemistry were all crucial elements of the SAR. Zatosetron maleate was a potent antagonist of 5HT-induced bradycardia in rats (ED50 = 0.86 micrograms/kg i.v.). Low oral doses of zatosetron (30 micrograms/kg) produced long-lasting antagonism of 5HT3 receptors, as evidenced by blockade of 5HT-induced bradycardia for longer than 6 h in rats. Moreover, this compound did not produce hemodynamic effects after i.v. administration to rats, nor did it block carbamylcholine-induced bradycardia in doses that markedly blocked 5HT3 receptors. Thus, zatosetron is a potent, selective, orally effective 5HT3 receptor antagonist with a long duration of action in rats.

  16. The treatment of neuroendocrine tumors with long-acting somatostatin analogs: a single center experience with lanreotide autogel.

    Science.gov (United States)

    Bianchi, A; De Marinis, L; Fusco, A; Lugli, F; Tartaglione, L; Milardi, D; Mormando, M; Lassandro, A P; Paragliola, R; Rota, C A; Della Casa, S; Corsello, S M; Brizi, M G; Pontecorvi, A

    2011-10-01

    The aim of this retrospective study was to evaluate the efficacy, safety, and tolerability of lanreotide autogel given to metastatic well-differentiated (WD) neuroendocrine tumors (NET) patients observed in our Institute between 2005 and 2008. Patients with metastatic NET referred to our tertiary referral center were given lanreotide autogel 120 mg/month by deep sc injection for a period of at least 24 months. The efficacy was evaluated by the relief of disease symptoms, behavior of tumor markers and response rate in terms of time to tumor progression. Safety and tolerability were evaluated by assessing the onset of adverse events and treatment feasibility. Twenty-three patients (13 males), median age 62 yr (range 32-87) were considered for the study. All patients were affected by WD metastatic NET and had tumor progression in the last 6 months before the enrolment in the study. Median duration of response was 28 months (range 6-50 months). Fourteen patients (60.9%) showed flushing and diarrhea which improved by 85.7% and 55.6%, respectively, bronchoconstrinction and abdominal pain also ameliorated. A complete, partial or no-changed response in the tumor markers behavior was observed, respectively, in 42.9%, 22.9%, and 17.1% of cases. According to RECIST (Response Evaluation Criteria In Solid Tumors) criteria (version 1.1), there were 2 partial regression (8.7%) and 15 stable disease (65.3%); 6 patients (26.0%) progressed. No patient complained from any severe adverse reaction. The results of our study suggest that lanreotide autogel is effective in the symptoms, biochemical markers, and tumor progression control of WD metastatic NET and confirm that the treatment is well tolerated.

  17. Clinical utility of orally disintegrating olanzapine in Chinese patients with schizophrenia: a review of effectiveness, patient preference, adherence, and other properties

    Directory of Open Access Journals (Sweden)

    Zhao J

    2014-02-01

    Full Text Available Jingping Zhao,1 Jianjun Ou,1 Haibo Xue,2 Li Liu,2 William Montgomery,3 Tamas Treuer4 1Mental Health Institute of The Second Xiangya Hospital, Hunan Province Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, Hunan, 2Lilly Suzhou Pharmaceutical Co, Ltd, Jiangsu, People's Republic of China; 3Global Health Outcomes, Eli Lilly and Company, Sydney, Australia; 4Emerging Markets Business Unit (Neuroscience, Eli Lilly and Company, Budapest, Hungary Abstract: The primary objective of this systematic review was to examine the evidence for the efficacy, effectiveness, and safety of orally disintegrating olanzapine in Chinese populations. A systematic literature search was conducted using databases covering international and Chinese journals, ClinicalTrials.gov, and internal and external trial registries at Eli Lilly and Company using search terms related to target countries (People's Republic of China, Hong Kong, and Taiwan and orally disintegrating olanzapine treatment. A publication and one clinical study report were retrieved. The clinical study showed orally disintegrating olanzapine and the standard oral tablet to have similar efficacy and tolerability profiles. A bioequivalence study has shown that orally disintegrating olanzapine and the standard oral tablet have similar pharmacokinetic profiles. Orally disintegrating olanzapine and the standard oral tablet have similar efficacy and tolerability profiles. Keywords: orally disintegrating, olanzapine, Chinese, schizophrenia, patients

  18. Case report of adjunctive use of olanzapine with an antidepressant to treat sleep paralysis

    Institute of Scientific and Technical Information of China (English)

    Jinfeng DUAN; Wanli HUANG; Mincong ZHOU; Xujuan LI; Wei CAI

    2013-01-01

    Sleep paralysis (SP) is a condiiton of unknown eitology that usually occurs when falling asleep or when awakening in which the individual remains conscious but is unable to control their voluntary movements. This case report is about a 68-year-old man with a 40-year history of symptoms of SP and associated panic attacks upon awakening. Neurological examination and neuroimaging identified no abnormaliites. Five years before the current evaluaiton he had been diagnosed with depression and treated with various anit-depressants which ameliorated, but did not cure, his SP. However, this 40-year history of SP was abruptly terminated-and did not return over the subsequent two years-atfer adjuncitve treatment with 2.5 mg olanzapine each night was added to his anitdepressant.

  19. Case report of adjunctive use of olanzapine with an antidepressant to treat sleep paralysis.

    Science.gov (United States)

    Duan, Jingfeng; Huang, Wanli; Zhou, Mincong; Li, Xujuan; Cai, Wei

    2013-10-01

    Sleep paralysis (SP) is a condition of unknown etiology that usually occurs when falling asleep or when awakening in which the individual remains conscious but is unable to control their voluntary movements. This case report is about a 68-year-old man with a 40-year history of symptoms of SP and associated panic attacks upon awakening. Neurological examination and neuroimaging identified no abnormalities. Five years before the current evaluation he had been diagnosed with depression and treated with various anti-depressants which ameliorated, but did not cure, his SP. However, this 40-year history of SP was abruptly terminated - and did not return over the subsequent two years - after adjunctive treatment with 2.5 mg olanzapine each night was added to his antidepressant.

  20. Change in level of productivity in the treatment of schizophrenia with olanzapine or other antipsychotics

    Directory of Open Access Journals (Sweden)

    Osuntokun Olawale

    2011-05-01

    Full Text Available Abstract Background When treating schizophrenia, improving patients' productivity level is a major goal considering schizophrenia is a leading cause of functional disability. Productivity level has been identified as the most preferred treatment outcome by patients with schizophrenia. However, little has been done to systematically investigate productivity levels in schizophrenia. We set out to better understand the change in productivity level among chronically ill patients with schizophrenia treated with olanzapine compared with other antipsychotic medications. We also assessed the links between productivity level and other clinical outcomes. Methods This post hoc analysis used data from 6 randomized, double-blind clinical trials of patients with schizophrenia or schizoaffective disorder, with each trial being of approximately 6 months duration. Change in productivity level was compared between olanzapine-treated patients (HGBG, n = 172; HGHJ, n = 277; HGJB, n = 171; HGLB, n = 281; HGGN, n = 159; HGDH, n = 131 and patients treated with other antipsychotic medications (separately vs. haloperidol [HGGN, n = 97; HGDH, n = 132], risperidone [HGBG, n = 167; HGGN, n = 158], quetiapine [HGJB, n = 175], ziprasidone [HGHJ, n = 271] and aripiprazole [HGLB, n = 285]. Productivity was defined as functional activities/work including working for pay, studying, housekeeping and volunteer work. Productivity level in the prior 3 months was assessed on a 5-point scale ranging from no useful functioning to functional activity/work 75% to 100% of the time. Results Chronically ill patients treated with olanzapine (OLZ experienced significantly greater improvement in productivity when compared to patients treated with risperidone (RISP (OLZ = 0.22 ± 1.19, RISP = -0.03 ± 1.17, p = 0.033 or ziprasidone (ZIP (OLZ = 0.50 ± 1.38, ZIP = 0.25 ± 1.27, p = 0.026, but did not significantly differ from the quetiapine, aripiprazole or haloperidol treatment groups. Among

  1. Estimated disability-adjusted life years averted by long-term provision of long acting contraceptive methods in a Brazilian clinic.

    Science.gov (United States)

    Bahamondes, Luis; Bottura, Bruna F; Bahamondes, M Valeria; Gonçalves, Mayara P; Correia, Vinicius M; Espejo-Arce, Ximena; Sousa, Maria H; Monteiro, Ilza; Fernandes, Arlete

    2014-10-10

    What is the contribution of the provision, at no cost for users, of long acting reversible contraceptive methods (LARC; copper intrauterine device [IUD], the levonorgestrel-releasing intrauterine system [LNG-IUS], contraceptive implants and depot-medroxyprogesterone [DMPA] injection) towards the disability-adjusted life years (DALY) averted through a Brazilian university-based clinic established over 30 years ago. Over the last 10 years of evaluation, provision of LARC methods and DMPA by the clinic are estimated to have contributed to DALY averted by between 37 and 60 maternal deaths, 315-424 child mortalities, 634-853 combined maternal morbidity and mortality and child mortality, and 1056-1412 unsafe abortions averted. LARC methods are associated with a high contraceptive effectiveness when compared with contraceptive methods which need frequent attention; perhaps because LARC methods are independent of individual or couple compliance. However, in general previous studies have evaluated contraceptive methods during clinical studies over a short period of time, or not more than 10 years. Furthermore, information regarding the estimation of the DALY averted is scarce. We reviewed 50 004 medical charts from women who consulted for the first time looking for a contraceptive method over the period from 2 January 1980 through 31 December 2012. Women who consulted at the Department of Obstetrics and Gynaecology, University of Campinas, Brazil were new users and users switching contraceptive, including the copper IUD (n = 13 826), the LNG-IUS (n = 1525), implants (n = 277) and DMPA (n = 9387). Estimation of the DALY averted included maternal morbidity and mortality, child mortality and unsafe abortions averted. We obtained 29 416 contraceptive segments of use including 25 009 contraceptive segments of use from 20 821 new users or switchers to any LARC method or DMPA with at least 1 year of follow-up. The mean (± SD) age of the women at first consultation ranged from 25

  2. Olanzapine treatment of adolescent rats causes enduring specific memory impairments and alters cortical development and function.

    Directory of Open Access Journals (Sweden)

    Jean A Milstein

    Full Text Available Antipsychotic drugs are increasingly used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of early life antipsychotic drug treatment. Most antipsychotic drugs are potent antagonists or partial agonists of dopamine D2 receptors; atypical antipsychotic drugs also antagonize type 2A serotonin receptors. Dopamine and serotonin regulate many neurodevelopmental processes. Thus, early life antipsychotic drug treatment can, potentially, perturb these processes, causing long-term behavioral- and neurobiological impairments. Here, we treated adolescent, male rats with olanzapine on post-natal days 28-49. As adults, they exhibited impaired working memory, but normal spatial memory, as compared to vehicle-treated control rats. They also showed a deficit in extinction of fear conditioning. Measures of motor activity and skill, habituation to an open field, and affect were normal. In the orbital- and medial prefrontal cortices, parietal cortex, nucleus accumbens core and dentate gyrus, adolescent olanzapine treatment altered the developmental dynamics and mature values of dendritic spine density in a region-specific manner. Measures of motor activity and skill, habituation to an open field, and affect were normal. In the orbital- and medial prefrontal cortices, D1 binding was reduced and binding of GABA(A receptors with open Cl(- channels was increased. In medial prefrontal cortex, D2 binding was also increased. The persistence of these changes underscores the importance of improved understanding of the enduring sequelae of pediatric APD treatment as a basis for weighing the benefits and risks of adolescent antipsychotic drug therapy, especially prophylactic treatment in high risk, asymptomatic patients. The long-term changes in neurotransmitter receptor binding and neural circuitry induced by adolescent APD treatment may also cause enduring changes in behavioral- and

  3. Demand for long acting and permanent methods of contraceptives and factors for non-use among married women of Goba Town, Bale Zone, South East Ethiopia

    Directory of Open Access Journals (Sweden)

    Takele Abulie

    2012-10-01

    Full Text Available Abstract Background Contraceptive use including short acting, long acting and permanent methods positively influence the socio-economic development of a nation by allowing families to space and limit their family size to their economic capacity. Demand for LAPMs of contraception as detrmined by utilization and unmet need for LAPMs of contraception can provide realiable information for providers. Objective To determine the utilization of long acting and permanent contraception and its associated factors among married women of Goba town, South East Ethiopia. Methods A cross sectional community based study was conducted among 734 systematically selected married women of reproductive age in Goba town in September/ 2009. A structured and pretested, interview questionaire was used to collect data on socio-demographic, behavioral factors and data related to demand for LAPMs of contraception. Data were analyzed using EPI INFO and SPSS version 16. Result The demand for Long Acting and Permanent Methods (LAPMs of contraception was 18.1%. Utilization of LAPMs of contraception in the town was 64 (8.7% and the unmet need for LAPMs was 69 (9.4%. Information on LAPMs in the town was 636 (86.6%. Media (radio and television was the major sources of information 641 (87.3%. The use of LAPMs was significatly associated with ever use AOR[17.43, 95% CI:9.19, 33.03], number of times discussions made on methods AOR[4.6, 95% CI: 1.72,12.17] and main decider of using methods AOR[ 2.2, 95% CI:1.03, 4.65]. It was not associated with socio-demographic variables. Conclusion and recommendation The utilization of LAPMs in the town was less although higher than the Ethiopian demographic and health survey 2005 result. Moreover, there was a considerable unmet need. Increase the method mix of LAPMs by incorporating varaies of implnats in order to increase utilization. Proper counseling of client and partners discussion were some of the recommendation forwarded.

  4. Risk of pneumonia with inhaled corticosteroid versus long-acting bronchodilator regimens in chronic obstructive pulmonary disease: a new-user cohort study.

    Directory of Open Access Journals (Sweden)

    Rachael L DiSantostefano

    Full Text Available INTRODUCTION: Observational studies using case-control designs have showed an increased risk of pneumonia associated with inhaled corticosteroid (ICS-containing medications in patients with chronic obstructive pulmonary disease (COPD. New-user observational cohort designs may minimize biases associated with previous case-control designs. OBJECTIVE: To estimate the association between ICS and pneumonia among new users of ICS relative to inhaled long-acting bronchodilator (LABD monotherapy. METHODS: Pneumonia events in COPD patients ≥45 years old were compared among new users of ICS medications (n = 11,555; ICS, ICS/long-acting β2-agonist [LABA] combination and inhaled LABD monotherapies (n = 6,492; LABA, long-acting muscarinic antagonists using Cox proportional hazards models, with propensity scores to adjust for confounding. SETTING: United Kingdom electronic medical records with linked hospitalization and mortality data (2002-2010. New users were censored at earliest of: pneumonia event, death, changing/discontinuing treatment, or end of follow-up. OUTCOMES: severe pneumonia (primary and any pneumonia (secondary. RESULTS: Following adjustment, new use of ICS-containing medications was associated with an increased risk of pneumonia hospitalization (n = 322 events; HR = 1.55, 95% CI: 1.14, 2.10 and any pneumonia (n = 702 events; HR = 1.49, 95% CI: 1.22, 1.83. Crude incidence rates of any pneumonia were 48.7 and 30.9 per 1000 person years among the ICS-containing and LABD cohorts, respectively. Excess risk of pneumonia with ICS was reduced when requiring ≥1 month or ≥ 6 months of new use. There was an apparent dose-related effect, with greater risk at higher daily doses of ICS. There was evidence of channeling bias, with more severe patients prescribed ICS, for which the analysis may not have completely adjusted. CONCLUSIONS: The results of this new-user cohort study are consistent with published findings; ICS were

  5. Mepolizumab Injection

    Science.gov (United States)

    ... or do not go away: pain, redness, swelling, warmth, burning, or itching in the place mepolizumab was injected headache dry and itchy skin with or without red, scaly rashes back pain muscle spasms Some side ...

  6. Metoclopramide Injection

    Science.gov (United States)

    ... and feeling of fullness that lasts long after meals. Metoclopramide injection is also used to prevent nausea ... tranylcypromine (Parnate); narcotic medications for pain; sedatives; sleeping pills; tetracycline (Bristacycline, Sumycin); tranquilizers. Your doctor may need ...

  7. Ramucirumab Injection

    Science.gov (United States)

    ... dose of ramucirumab injection. Tell your doctor or nurse if you experience any of the following while you receive ramucirumab: uncontrollable shaking of a part of the body; back pain or spasms; chest pain and tightness; chills; flushing; ...

  8. Alemtuzumab Injection

    Science.gov (United States)

    Alemtuzumab injection is used to treat B-cell chronic lymphocytic leukemia (a slowly developing cancer in which ... of white blood cell accumulate in the body). Alemtuzumab is in a class of medications called monoclonal ...

  9. Ferumoxytol Injection

    Science.gov (United States)

    Ferumoxytol injection is used to treat iron-deficiency anemia (a lower than normal number of red blood ... pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or ...

  10. Fludarabine Injection

    Science.gov (United States)

    Fludarabine injection is used to treat chronic lymphocytic leukemia (CLL; a type of cancer of the white ... a reliable method of birth control to prevent pregnancy during this time. Talk to your doctor for ...

  11. Insulin Injection

    Science.gov (United States)

    ... or buttocks. Do not inject insulin into muscles, scars, or moles. Use a different site for each ... you are using insulin.Alcohol may cause a decrease in blood sugar. Ask your doctor about the ...

  12. Tigecycline Injection

    Science.gov (United States)

    ... in a person who was not in the hospital), skin infections, and infections of the abdomen (area between the ... that developed in people who were in a hospital or foot infections in people who have diabetes. Tigecycline injection is ...

  13. Golimumab Injection

    Science.gov (United States)

    Golimumab injection is used alone or with other medications to relieve the symptoms of certain autoimmune disorders ( ... did not help or could not be tolerated. Golimumab is in a class of medications called tumor ...

  14. Albiglutide Injection

    Science.gov (United States)

    ... will develop tumors of the thyroid gland, including medullary thyroid carcinoma (MTC; a type of thyroid cancer). ... symptoms or those listed in the IMPORTANT WARNING section, stop using albiglutide injection and call your doctor ...

  15. Dexamethasone Injection

    Science.gov (United States)

    ... body tissues,) gastrointestinal disease, and certain types of arthritis. Dexamethasone injection is also used for diagnostic testing. ... effects.tell your doctor if you have a fungal infection (other than on your skin or nails). ...

  16. Hydrocortisone Injection

    Science.gov (United States)

    ... own organs), gastrointestinal disease, and certain types of arthritis. Hydrocortisone injection is also used to treat certain ... effects.tell your doctor if you have a fungal infection (other than on your skin or nails). ...

  17. Methylprednisolone Injection

    Science.gov (United States)

    ... own organs), gastrointestinal disease, and certain types of arthritis. Methylprednisolone injection is also used to treat certain ... effects.tell your doctor if you have a fungal infection (other than on your skin or nails). ...

  18. Glatiramer Injection

    Science.gov (United States)

    ... To inject glatiramer, follow these steps: Remove one blister pack from the carton of glatiramer syringes and place ... paper label and remove the syringe from the blister pack. Check your prefilled syringe to be sure it ...

  19. Dexrazoxane Injection

    Science.gov (United States)

    ... that are used to treat or prevent certain side effects that may be caused by chemotherapy medications. Dexrazoxane injection (Zinecard) is used to prevent or decrease heart damage caused by doxorubicin in women who are ...

  20. Evolocumab Injection

    Science.gov (United States)

    ... autoinjector in hot water, microwave, or place in sunlight.Before you use evolocumab injection, look at the ... chills pain or burning during urination muscle or back pain dizziness stomach pain Some side effects can be ...

  1. Cidofovir Injection

    Science.gov (United States)

    Cidofovir injection is used along with another medication (probenecid) to treat cytomegaloviral retinitis (CMV retinitis) in people with acquired immunodeficiency syndrome (AIDS). Cidofovir is in a class of medications called antivirals. ...

  2. Brivaracetam Injection

    Science.gov (United States)

    ... older. Brivaracetam in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in ... older (about 1 in 500 people) who took anticonvulsants like brivaracetam injection to treat various conditions during ...

  3. Diphenhydramine Injection

    Science.gov (United States)

    ... not to use diphenhydramine injection if you are breastfeeding because of the risk of harm to infants.tell your doctor if you have or have ever had asthma or other types of lung disease; glaucoma (a ...

  4. Cefazolin Injection

    Science.gov (United States)

    ... valve, respiratory tract (including pneumonia), biliary tract, and urinary tract infections. Cefazolin injection also may be used before, during, ... to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website ( ...

  5. Ceftazidime Injection

    Science.gov (United States)

    ... skin, blood, bone, joint, female genital tract, and urinary tract infections. Ceftazidime injection is in a class of medications ... to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website ( ...

  6. Fluconazole Injection

    Science.gov (United States)

    ... and fungal infections of the eye, prostate (a male reproductive organ), skin and nails. Fluconazole injection is ... Motrin, others) and naproxen (Aleve, Anaprox, Naprelan); oral contraceptives (birth control pills); oral medication for diabetes such ...

  7. Moxifloxacin Injection

    Science.gov (United States)

    ... available.Moxifloxacin injection is in a class of antibiotics called fluoroquinolones. It works by killing the bacteria that cause ... you are allergic to moxifloxacin, other quinolone or fluoroquinolone antibiotics such as ciprofloxacin (Cipro), gatifloxacin (Tequin) (not available ...

  8. Levofloxacin Injection

    Science.gov (United States)

    ... available. Levofloxacin injection is in a class of antibiotics called fluoroquinolones. It works by killing bacteria that cause infections. ... severe reaction to levofloxacin; any other quinolone or fluoroquinolone antibiotic such as ciprofloxacin (Cipro), gatifloxacin (Tequin) (not available ...

  9. Ciprofloxacin Injection

    Science.gov (United States)

    ... available. Ciprofloxacin injection is in a class of antibiotics called fluoroquinolones. It works by killing bacteria that cause infections. ... reaction to ciprofloxacin or any other quinolone or fluoroquinolone antibiotic such as gatifloxacin (Tequin) (not available in the ...

  10. Alirocumab Injection

    Science.gov (United States)

    ... further decrease the amount of low-density lipoprotein (LDL) cholesterol ('bad cholesterol') in the blood. Alirocumab injection is ... antibodies. It works by blocking the production of LDL cholesterol in the body to decrease the amount of ...

  11. Chloramphenicol Injection

    Science.gov (United States)

    ... an arm or leg sudden changes in vision pain with eye movement Chloramphenicol injection may cause a condition called gray syndrome in premature and newborn infants. There have also been reports of gray ...

  12. Betahistine co-treatment ameliorates dyslipidemia induced by chronic olanzapine treatment in rats through modulation of hepatic AMPKα-SREBP-1 and PPARα-dependent pathways.

    Science.gov (United States)

    Liu, Xuemei; Lian, Jiamei; Hu, Chang-Hua; Deng, Chao

    2015-10-01

    Second-generation antipsychotics including olanzapine are associated with weight gain, dyslipidemia and other metabolic disorders. Both animal and clinical studies have shown that co-treatment with betahistine (a histamine H1 receptor agonist/H3 receptor antagonist) is effective in controlling olanzapine-induced weight gain. In the present study, we investigate whether co-treatment with betahistine is able to prevent dyslipidemia induced by chronic olanzapine treatment and the underlying mechanisms. Female rats were orally administered with olanzapine (1 mg/kg, t.i.d.) for 3.5 consecutive weeks and then a 2.5-week drug withdrawal. Then, rats were divided into 4 groups for 5 weeks treatment: (1) vehicle, (2) olanzapine-only (1 mg/kg, t.i.d.), (3) betahistine-only (9.6 mg/kg, t.i.d.), and (4) olanzapine and betahistine (O+B) co-treatment. After completing treatment, hepatic mRNA expression was measured by qRT-PCR, while the protein levels were detected by western blot. In our study, olanzapine-only treatment significantly increased triglyceride accumulation and non-esterified fatty acids (NEFA), and upregulated mRNA expression of sterol regulatory element binding protein 1 (SREBP-1) and its target genes, while these alterations were ameliorated by O+B co-treatment. Hepatic AMP-activated protein kinase α (AMPKα) was activated in the O+B co-treatment group, with a significant reduction in nuclear SREBP-1 protein expression but an increased expression of peroxisome proliferator-activated receptor-α (PPARα) and its-responsive molecule(CPT1A), compared with olanzapine-only treatment. In addition, olanzapine significantly increased hepatic histamine H1 receptors, while O+B co-treatment significantly reversed them to normal levels. This study provided the first evidence that betahistine could act on hepatic H1 receptors via modulation of AMPKα-SREBP-1 and PPARα-dependent pathways to ameliorate olanzapine-induced dyslipidemia in rats.

  13. A VALIDATED RP-HPLC METHOD FOR THE SIMULTANEOUS ESTIMATION OF FLUOXETINE HYDROCHLORIDE AND OLANZAPINE IN PHARMACEUTICAL DOSAGE FORM

    Directory of Open Access Journals (Sweden)

    M.M.Eswarudu

    2012-04-01

    Full Text Available A simple, sensitive and precise reverse phase high performance liquid chromatographic method has been developed for the simultaneous estimation of Fluoxetine hydrochloride and Olanzapine in pharmaceutical dosage forms. The mobile phase consisted of Acetonitrile: pot.dihydrogen phosphate buffer: Triethylamine (0.2 % (0.1% v/v ortho phosphoric acid, PH 3.1 in the ratio of 40:60:0.2 v/v/v delivered at a flow rate of 1.0 ml / min and wavelength of detection at 233 nm. The retention times of Fluoxetine and Olanzapine were 1.96 min and 5.59 min respectively. The developed method was validated according to ICH guidelines. The proposed method can be used for determination of these drugs in combined dosage forms.

  14. Simultaneous Estimation of Fluoxetine HCl and Olanzapine in Bulk Drug and Pharmaceutical Formulation by Using UV-Visible Spectroscopy Method

    Directory of Open Access Journals (Sweden)

    Rubesh kumar S

    2011-01-01

    Full Text Available Present work is to carry out an analytical method development and validation of Fluoxetine HCl (FLU and Olanzapine (OLZ in bulk drug and pharmaceutical dosage form. The developed method is based upon simultaneous equations (Vierodt’s method by using UV/Visible spectroscopy. Both drugs come in the categories of anti- depressant and anti-psychotic agent. The developed method can be used for the simultaneous estimation of FLU and OLZ in pharmaceutical dosage form without separating from each other or from the excipients. Primarily the λ max of Fluoxetine HCl (FLU and Olanzapine (OLZ was determined as 226 and 258 nm respectively. The suggested method is validated by using ICH validation parameters like accuracy, precession, linearity and LOD and LOQ respectively. Accuracy study showed percentage recovery in the range of 97-102% w/w respectively. Precision studies were carried out for 6 successive absorbance and studied for their percentage relative standard deviation (%RSD was < 2%, LOD and LOQ was studied and the limit of detection and limit of quantification were found to be was 1-100 µg/ml for Olanzapine and Fluoxetine HCl, the slope of interception Y=0.23x6+0.054 (R2 0.993 and Y=0.222x6-0.014 (R 2 0.995 respectively. Relative standard deviation for Fluoxetine hydrochloride and Olanzapine were 0.4904 and 0.53969, the co-relation coefficient were 0.997 and 0.825 respectively. This procedure was applied successfully for the analysis of FLU and OLZ in bulk drug and Pharmaceutical preparations.

  15. Effects of quetiapine and olanzapine in patients with psychosis and violent behavior: a pilot randomized, open-label, comparative study

    Directory of Open Access Journals (Sweden)

    Gobbi G

    2014-05-01

    Full Text Available Gabriella Gobbi,1,2 Stefano Comai,1 Guy Debonnel1,2,† 1Neurobiological Psychiatric Unit, Department of Psychiatry, McGill University and McGill University Health Center, 2Institut Philippe Pinel, Department of Psychiatry, Université de Montréal, Montréal, QC, Canada †Guy Debonnel passed away on November 4, 2006 Objective: Patients suffering from psychosis are more likely than the general population to commit aggressive acts, but the therapeutics of aggressive behavior are still a matter of debate. Methods: This pilot randomized, open-label study compared the efficacy of quetiapine versus olanzapine in reducing impulsive and aggressive behaviors (primary endpoints and psychotic symptoms (secondary endpoints from baseline to days 1, 7, 14, 28, 42, 56, and 70, in 15 violent schizophrenic patients hospitalized in a maximum-security psychiatric hospital. Results: Quetiapine (525±45 mg and olanzapine (18.5±4.8 mg were both efficacious in reducing Impulsivity Rating Scale from baseline to day 70. In addition, both treatments reduced the Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale, and Clinical Global Impression Scale scores at day 70 compared to baseline, and no differences were observed between treatments. Moreover, quetiapine, but not olanzapine, yielded an improvement of depressive symptoms in the items “depression” in Brief Psychiatric Rating Scale and “blunted affect” in Positive and Negative Syndrome Scale. Modified Overt Aggression Scale scores were also decreased from baseline to the endpoint, but due to the limited number of patients, it was not possible to detect a significant difference. Conclusion: In this pilot study, quetiapine and olanzapine equally decreased impulsive and psychotic symptoms after 8 weeks of treatment. Double-blind, large studies are needed to confirm the validity of these two treatments in highly aggressive and violent schizophrenic patients. Keywords: schizophrenia, aggression

  16. Fabrication of long-acting drug release property of hierarchical porous bioglasses/polylactic acid fibre scaffolds for bone tissue engineering.

    Science.gov (United States)

    Wang, Dan; Lin, Huiming; Jiang, Jingjie; Jin, Qumei; Li, Lei; Dong, Yan; Qu, Fengyu

    2015-04-01

    Hierarchical porous fibre scaffolds with mesoporous bioglasses (MBGs) and polylactic acid (PLA) were successfully fabricated by the electrospinning method. These compound scaffolds possess macropores with sizes of about 100 nm because of the solvent evaporation from the fibre and the mesoporous structure ( ∼4.0 nm) originated from MBGs. The biomineralisation ability was investigated in simulated body fluid. The fibre structure is beneficial for inducing the growth of hydroxyapatite. In addition, compared with pure MBGs, the materials (MP-1 and MP-2) exhibit a long-acting drug release process up to 140 h and the drug release process corresponds with the Fickian diffusion mechanism. With the special fibre morphology and the hierarchical porous structure, the MBGs/PLA fibre scaffolds are expected to have potential application for bone tissue repair and regeneration.

  17. Efficacy and safety of long-acting pasireotide in Japanese patients with acromegaly or pituitary gigantism: results from a multicenter, open-label, randomized, phase 2 study.

    Science.gov (United States)

    Tahara, Shigeyuki; Murakami, Mami; Kaneko, Tomomi; Shimatsu, Akira

    2017-07-28

    A multicenter, open-label, phase 2 study was conducted to investigate the efficacy and safety of long-acting pasireotide formulation in Japanese patients with acromegaly or pituitary gigantism. Medically naïve or inadequately controlled patients (on somatostatin analogues or dopamine agonists) were included. Primary end point was the proportion of all patients who achieved biochemical control (mean growth hormone [GH] levelsacromegaly, n=32; pituitary gigantism, n=1) were enrolled and randomized 1:1:1 to receive open-label pasireotide 20mg, 40mg, or 60mg. The median age was 52 years (range, 31-79) and 20 patients were males. At month 3, 18.2% of patients (6/33; 90% confidence interval: 8.2%, 32.8%) had biochemical control (21.2% [7/33] when including a patient with mean GHacromegaly or pituitary gigantism.

  18. Hormonal secretion and quality of life in Nelson syndrome and Cushing disease after long acting repeatable octreotide: a short series and update.

    Science.gov (United States)

    Arregger, Alejandro L; Cardoso, Estela M L; Sandoval, Olga B; Monardes Tumilasci, Elida G; Sanchez, Rocío; Contreras, Liliana N

    2014-01-01

    Clinical management of persistent adrenocorticotropin hormone (ACTH) excess in Nelson syndrome (NS) and Cushing disease (CD) remains a challenge. Somatostatin and its analogs as octreotide decrease ACTH secretion through somatostatin receptors of pituitary cells. To our knowledge, there are no reports on the effect of long-acting repeatable octreotide (oct-lar) on hormonal secretion and quality of life in patients with NS and CD who failed conventional therapy. Herein, we describe the effects of treatment with oct-lar (20 mg/month intramurally) in 1 woman with NS and 2 women with persistent CD. Oct-lar therapy reduced ACTH secretion and improved the quality of life in NS patient. By contrast, in CD patients, it failed to control ACTH and cortisol secretion, and the quality of life remained unchanged.

  19. Profiling the bronchodilator effects of the novel ultra-long-acting β2-agonist indacaterol against established treatments in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Vogelmeier, Claus; Magnussen, Helgo; LaForce, Craig; Owen, Roger; Kramer, Benjamin

    2011-10-01

    Indacaterol is a novel, inhaled, ultra-long-acting β(2)-agonist providing 24-h bronchodilation with once-daily (od) dosing for maintenance use in patients with chronic obstructive pulmonary disease (COPD). This article reviews the bronchodilator properties of indacaterol compared with other treatments used in COPD. Data from five published placebo-controlled studies were reviewed. Two 14-day crossover studies, the first comparing indacaterol 300 µg od with salmeterol 50 µg twice daily (bid), the second comparing indacaterol 150 µg and 300 µg od with tiotropium 18 µg od, assessed forced expiratory volume in 1 s (FEV(1)) at 24 h postdose (trough). Third, a 14-day crossover study evaluated trough FEV(1) following indacaterol 300 µg dosed morning or evening compared with salmeterol 50 µg bid. Fourth, a single-dose study of indacaterol 150 and 300 µg measured FEV(1) at 5 min postdose compared with salmeterol/fluticasone 50/500 µg and salbutamol 200 µg. Finally, data from a 1-year study with indacaterol 300 µg and formoterol 12 µg bid were examined to determine whether bronchodilation was maintained long term. In the first two studies, indacaterol increased trough FEV(1) after 14 days by a statistically significant and clinically relevant margin over placebo; indacaterol had a greater effect than salmeterol and a similar effect to tiotropium. In the third study, indacaterol had the same effect on trough FEV(1) whether dosed in the morning or evening. In the fourth study, the onset of the bronchodilator effect of indacaterol was similar to that of salbutamol. In the fifth study, the bronchodilator effect of indacaterol on trough FEV(1) was maintained at a significant and clinically relevant level over 52 weeks, whereas the bronchodilator effect of formoterol diminished over time. To conclude, indacaterol is a highly effective bronchodilator that is superior to or at least as effective as other available long-acting bronchodilators for COPD.

  20. Association study of olanzapine-induced weight gain and therapeutic response with SERT gene polymorphisms in female schizophrenic patients.

    Science.gov (United States)

    Bozina, Nada; Medved, Vesna; Kuzman, Martina Rojnic; Sain, Ivica; Sertic, Jadranka

    2007-09-01

    We investigated the relationships between L/S promoter (SERTPR) and l/s intron2 (SERTin2) genetic variants of serotonin transporter (SERT) polymorphisms with olanzapine-induced weight gain and treatment response in 94 female schizophrenic patients treated with olanzapine for up to 3 months. Body mass index (BMI) was calculated for each patient prior to olanzapine administration and 3 months afterwards. To assess and evaluate improvement of clinical psychotic symptoms and therapeutic response to the antipsychotic, all patients were rated using the Positive and Negative Syndrome ScaLe (PANSS). Overall, the presence of S SERTPR allelic variant and SS genotype was associated with significantly higher weight gain in subjects who were non-obese at the time of admission. The presence of L SERTPR variant was associated with significantly better treatment response measured with total PANSS and general PANSS subscale, while the presence of l SERTin2 variant determined better treatment response only in several items. No evidence of linkage disequilibrium between the two loci was found in the sample. These findings identify genetic factors associated with oLanzapine-induced weight gain and treatment response in femaLe schizophrenic patients.

  1. Olanzapine and Betamethasone Are Effective for the Treatment of Nausea and Vomiting due to Metastatic Brain Tumors of Rectal Cancer

    Directory of Open Access Journals (Sweden)

    M. Suzuki

    2014-01-01

    Full Text Available Brain lesions originating from metastasis of colorectal cancer represent 3-5% of all brain metastases and are relatively rare. Of all distant metastases of colorectal cancer, those to the liver are detected in 22-29% of cases, while those to the lungs are detected in 8-18% of cases. In contrast, brain metastasis is quite rare, with a reported incidence ranging from 0.4 to 1.8%. Treatments for metastatic brain tumors include surgery, radiotherapy, chemotherapy and supportive care with steroids, etc. Untreated patients exhibit a median survival of only approximately 1 month. The choice of treatment for brain metastasis depends on the number of lesions, the patient's general condition, nerve findings and presence of other metastatic lesions. We herein report the case of a 78-year-old male who presented with brain metastases originating from rectal carcinoma. He suffered from nausea, vomiting, anorexia and vertigo during body movement. He received antiemetics, glycerol and whole brain radiation therapy; however, these treatments proved ineffective. Olanzapine therapy was started at a dose of 1.25 mg every night. The persistent nausea disappeared the next day, and the frequency of vomiting subsequently decreased. The patient was able to consume solid food. Olanzapine is an antipsychotic that has recently been used as palliative therapy for refractory nausea and vomiting in patients receiving chemotherapy. We consider that olanzapine was helpful as a means of supportive care for the treatment of nausea and vomiting due to brain metastasis.

  2. A Randomized, Double-Blind, Placebo-Controlled Pilot Study of Betahistine to Counteract Olanzapine-Associated Weight Gain.

    Science.gov (United States)

    Barak, Nir; Beck, Yaffa; Albeck, Joseph H

    2016-06-01

    Patients with schizophrenia experience higher rates of obesity and related morbidity and mortality than the general population does. Given preclinical studies revealing the role of histamine H1 receptor in human eating behavior, and the potential of olanzapine to block with this system, we hypothesized that histamine H1 receptor agonists may be beneficial in reducing antipsychotic-associated weight gain. In the present study, 36 patients with a diagnosis of schizophrenia or schizoaffective disorder and treated with olanzapine were randomized to betahistine (48 mg/d) or matching placebo for 16 weeks. Study outcomes were change in body weight from baseline and effect on antipsychotic efficacy of olanzapine. The patients in the betahistine group had less weight gain (-1.95 kg) compared with placebo group (5.6 + 5.5 kg vs 6.9 + 5.6 kg, respectively). Positive and Negative Syndrome Scale Questionnaire showed improvement within each group and that subjects treated with betahistine enjoyed an improvement (reduction) by a mean of 35.7 points, higher when compared with placebo subjects who had a reduction of 26.6 points (P = 0.233). An almost equal amount of subjects in both groups experienced adverse effects during the course of this study (87.5% of betahistine vs 85.0% of placebo-treated subjects). Overall, there were no clinically marked differences in safety signals between both groups. A larger study addressing the weaknesses of this pilot study is warranted.

  3. 奥氮平与氟哌啶醇治疗老年性谵妄的随机对照观察%Olanzapine and haloperidol for senile delirium: A randomized controlled observation

    Institute of Scientific and Technical Information of China (English)

    胡华; 邓伟; 杨辉; 刘玉

    2006-01-01

    啶醇组次之,对照组起效最慢(P<0.01).结论:奥氮平与氟哌啶醇治疗老年性谵妄疗效相当,但奥氮平起效更快.%BACKGROUND: Delirium is an acute organic brain syndrome caused by various reasons, and it is common in elderly patients. Antipsychotics treatment is an important method to control delirium.OBJECTIVE: To observe the efficacy of new antipsychotic agent of olanzapine and the traditional antipsychotic agent of haloperidol in treating senile delirium.DESIGN: A randomized controlled observation. SETTING: Mental Health Center, the First Affiliated Hospital of Chongqing University of Medical Sciences.PARTICIPANTS: Totally 175 inpatients with senile delirium were selected from the First Affiliated Hospital of Chongqing University of Medical Sciences from September 2001 to September 2003, they were randomly divided into olanzapine treatment group (n=74), haloperidol treatment group (n=72) and a control group(n=29). There were 111 males (63.4%) and 64 females (36.6%). Delirium had occurred for a duration of 30 minutes to 17 days, with an average of (3.02±2.71) days. The enrolled patients were classified according to the etiological factors of delirium: metabolic (n=68), toxic (n=47), structural (n=25) and infectious (n=35).METHODS: Different treatments were used in different groups. Control group (n=29): The patients were only given somatic treatment aiming at delirium, and not any drug for central nervous system was used. Olanzapine group (n=74): Besides the somatic treatment aiming at delirium, the patients were given olanzapine (Zyprexa, produced by Eli Lilly and Company,5 mg/tablet) taken orally or sublingually (fasted patients), the initial dosage was 1.25-2.5 mg per day, and then adjusted to 1.25-20 mg per day. Haloperidol group (n=72): Besides the somatic treatment aiming at delirium, they were treated with intramuscular injection of haloperidol (2.5-10 mg per day). The effects were prospectively observed for 1 week.The scores were observed before enrollment

  4. Predictors of continuation with olanzapine during the 1-year naturalistic treatment of patients with schizophrenia in Japan

    Directory of Open Access Journals (Sweden)

    Ye W

    2011-12-01

    Full Text Available Wenyu Ye1, Haya Ascher-Svanum2, Yuka Tanji3, Jennifer A Flynn3, Michihiro Takahashi3,41Lilly Suzhou Pharmaceutical Co, Shanghai, People’s Republic of China; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories Japan, Eli Lilly Japan KK, Kobe, 4Terauchi-Takahashi Psychiatric Clinic, Ashiya, JapanPurpose: Treatment continuation is considered an important measure of antipsychotic effectiveness in schizophrenia, reflecting the medication’s efficacy, safety, and tolerability from both patients’ and clinicians’ perspectives. This study identified characteristics of patients with schizophrenia who continue olanzapine therapy for a 1-year period in Japan.Methods: In a large (N = 1850, prospective, observational study, Japanese patients with schizophrenia who initiated treatment with olanzapine were followed for 1 year. Baseline characteristics were compared using t-tests and chi-square tests. Stepwise logistic regression was used to identify independent baseline predictors of treatment continuation.Results: Most patients (68.2% continued with olanzapine therapy for the full 1-year study period, with an average duration of 265.5 ± 119.4 days. At baseline, patients who continued were significantly more likely to be male, older, and inpatients; have longer illness duration, higher negative and cognitive symptoms, better health-related quality of life, and prior anticholinergic use. Continuers were significantly less likely to engage in social activities, live independently, work for pay, or have prior antidepressant use. Continuers showed significantly greater early (3-month improvement in global symptom severity. Logistic regression found that continuation was significantly predicted by longer illness duration, lower positive symptoms, higher negative symptoms, and better health-related quality of life.Conclusions: In this large naturalistic study in Japan, most patients with schizophrenia stayed on olanzapine therapy for

  5. A double blind, placebo-controlled, randomized crossover study of the acute metabolic effects of olanzapine in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Vance L Albaugh

    Full Text Available Atypical antipsychotics exhibit metabolic side effects including diabetes mellitus and obesity. The adverse events are preceded by acute worsening of oral glucose tolerance (oGTT along with reduced plasma free fatty acids (FFA and leptin in animal models. It is unclear whether the same acute effects occur in humans.A double blind, randomized, placebo-controlled crossover trial was conducted to examine the potential metabolic effects of olanzapine in healthy volunteers. Participants included male (8 and female (7 subjects [18-30 years old, BMI 18.5-25]. Subjects received placebo or olanzapine (10 mg/day for three days prior to oGTT testing. Primary endpoints included measurement of plasma leptin, oral glucose tolerance, and plasma free fatty acids (FFA. Secondary metabolic endpoints included: triglycerides, total cholesterol, high- and low-density lipoprotein cholesterol, heart rate, blood pressure, body weight and BMI. Olanzapine increased glucose Area Under the Curve (AUC by 42% (2808±474 vs. 3984±444 mg/dl·min; P = 0.0105 during an oGTT. Fasting plasma leptin and triglycerides were elevated 24% (Leptin: 6.8±1.3 vs. 8.4±1.7 ng/ml; P = 0.0203 and 22% (Triglycerides: 88.9±10.1 vs. 108.2±11.6 mg/dl; P = 0.0170, whereas FFA and HDL declined by 32% (FFA: 0.38±0.06 vs. 0.26±0.04 mM; P = 0.0166 and 11% (54.2±4.7 vs. 48.9±4.3 mg/dl; P = 0.0184, respectively after olanzapine. Other measures were unchanged.Olanzapine exerts some but not all of the early endocrine/metabolic changes observed in rodent models of the metabolic side effects, and this suggest that antipsychotic effects are not limited to perturbations in glucose metabolism alone. Future prospective clinical studies should focus on identifying which reliable metabolic alterations might be useful as potential screening tools in assessing patient susceptibility to weight gain and diabetes caused by atypical antipsychotics.ClinicalTrials.gov NCT00741026.

  6. Successful management of stuttering priapism using home self-injections of the alpha-agonist metaraminol

    Directory of Open Access Journals (Sweden)

    Mcdonald Michael

    2004-01-01

    Full Text Available Low-flow priapism can result in impotence if treatment is delayed, yet patients with recurrent priapism often suffer delay before therapy. We describe management of recurrent priapism using self-administered injections of intracavernosal metaraminol (Aramine™, Merck, a long-acting vasoconstricting amine that is considered safer than epinephrine. The patient injects as often as once daily using 5-10 mg of drug. Our patient reports rapid detumescence and has not required emergency room visits since starting injections. He denies complications. Treatment of priapism using metaraminol has been suggested in the hospital setting; however, this is the first report of successful home self-administration of the drug.

  7. Sarilumab Injection

    Science.gov (United States)

    ... the needle. Do not try to warm the medication by heating it in a microwave, placing it in warm water or in direct sunlight, or through any other method.Before injecting, check the prefilled syringe to be sure that the expiration date printed on the package has not passed. Look ...

  8. Enfuvirtide Injection

    Science.gov (United States)

    ... inject enfuvirtide into any skin that has a tattoo, scar, bruise, mole, a burn site, or has ... Enfuvirtide may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: itching, swelling, pain, tingling, discomfort, ...

  9. Fluorouracil Injection

    Science.gov (United States)

    ... of a doctor who is experienced in giving chemotherapy medications for cancer. Treatment with fluorouracil injection may cause serious side effects. ... this medication.If you experience a serious side effect, you or your doctor ... (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/ ...

  10. Lanreotide Injection

    Science.gov (United States)

    Lanreotide injection is used to treat people with acromegaly (condition in which the body produces too much growth hormone, causing enlargement of the hands, feet, and facial features; joint pain; and other symptoms) who have not successfully, or cannot be treated ...

  11. Paliperidone Injection

    Science.gov (United States)

    ... the body slow movements or shuffling walk painful erection of the penis that lasts for hours cough, chills and/or other signs of infection Paliperidone injection may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.If you experience a ...

  12. Ziprasidone Injection

    Science.gov (United States)

    ... stiffness falling confusion sweating loss of consciousness painful erection of the penis that lasts for hours Ziprasidone injection may cause other side effects. Call your doctor if you have any unusual problems while receiving this medication.If you experience a ...

  13. Risperidone Injection

    Science.gov (United States)

    ... control slow movements or shuffling walk falling painful erection of the penis that lasts for hours Risperidone extended-release injection may cause other side effects. Call your doctor if you have any unusual problems while receiving this medication.If you experience a ...

  14. Long-acting muscarinic antagonists

    DEFF Research Database (Denmark)

    Busse, William W; Dahl, Ronald; Jenkins, Christine;

    2016-01-01

    -acting anticholinergics as bronchodilators in the treatment of asthma, with results published from clinical trials of glycopyrrolate, umeclidinium and tiotropium. The tiotropium clinical trial programme is the most advanced, with data available from a number of phase II and III studies of tiotropium as an add...... and children with asthma. Tiotropium Respimat has recently been incorporated into the Global Initiative for Asthma 2015 treatment strategy as a recommended alternative therapy at steps 4 and 5 in adult patients with a history of exacerbations. The increasing availability of evidence from ongoing and future...

  15. Comparative efficacy of long-acting β2-agonists as monotherapy for chronic obstructive pulmonary disease: a network meta-analysis

    Directory of Open Access Journals (Sweden)

    Donohue JF

    2017-01-01

    Full Text Available James F Donohue,1 Keith A Betts,2 Ella Xiaoyan Du,2 Pablo Altman,3 Pankaj Goyal,4 Dorothy L Keininger,4 Jean-Bernard Gruenberger,4 James E Signorovitch5 1Department of Pulmonary Diseases and Critical Care Medicine, The University of North Carolina, Chapel Hill, NC, 2Analysis Group, Inc., Los Angeles, CA, 3Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 4Novartis Pharma AG, Basel, Switzerland; 5Analysis Group, Inc., Boston, MA, USA Purpose: Long-acting β2-agonists (LABAs have demonstrated efficacy in patients with COPD in clinical trials. The purpose of this study was to assess the comparative efficacy of all available dosages of all LABA monotherapies using a network meta-analysis.Methods: A systematic literature review identified 33 randomized controlled trials of LABA monotherapies (salmeterol 50 µg twice daily [BID]; formoterol 12 µg BID; indacaterol 75, 150, and 300 µg once daily [OD]; olodaterol 5 and 10 µg OD, and vilanterol 25 µg OD. Clinical efficacy was evaluated at 12 and 24 weeks in terms of trough forced expiratory volume in 1 second (FEV1, transition dyspnea index focal score, St George’s Respiratory Questionnaire total score, and rate of COPD exacerbations. The relative effectiveness of all LABA monotherapies was estimated by Bayesian network meta-analysis.Results: At 12 and 24 weeks, indacaterol 300 and 150 µg OD were associated with statistically significant improvement in trough FEV1 compared to all other LABA monotherapies; vilanterol 25 µg OD was superior to formoterol 12 µg BID. At 12 weeks, indacaterol 75 µg OD was associated with significant improvement in trough FEV1 compared to formoterol 12 µg BID and olodaterol (5 and 10 µg OD; salmeterol 50 µg BID was superior to formoterol 12 µg BID and olodaterol 5 µg OD. Indacaterol 300 µg OD was also associated with significant improvement in transition dyspnea index focal score compared to all other LABAs at 12 or 24 weeks. Indacaterol 150 µg OD had

  16. Long acting β2 agonists for stable chronic obstructive pulmonary disease with poor reversibility: a systematic review of randomised controlled trials

    Directory of Open Access Journals (Sweden)

    Mensinkai Shaila

    2004-08-01

    Full Text Available Abstract Background The long acting β2-agonists, salmeterol and formoterol, have been recommended, by some, as first line treatment of stable chronic obstructive pulmonary disease (COPD. We reviewed evidence of efficacy and safety when compared with placebo or anticholinergic agents in patients with poorly reversible COPD. Methods After searching MEDLINE, EMBASE, HealthSTAR, BIOSIS Previews, PASCAL, ToxFile, SciSearch, the Cochrane Library, and PubMed, as well as Web sites, selected journals, reference lists, and contacting drug manufacturers, two reviewers independently screened reports of randomised controlled trials of parallel or crossover design lasting four weeks or longer and including patients with a forced expiratory volume in one second (FEV1 ≤ 75% of predicted, a ratio of FEV1 to forced vital capacity (FVC ≤ 88% of predicted, and Results Twelve trials satisfied our inclusion criteria; eight were high quality (Jadad score >2 and four were low quality (≤ 2. The adequacy of allocation concealment was unclear in all of them. We did not perform a meta-analysis due to differences in trial design and how outcomes were reported. Two trials comparing salmeterol with ipratropium did not detect differences; one trial comparing formoterol and ipratropium described greater improvement with formoterol in morning PEFR (15.3 versus 7.1 l/min, p = 0.040. Of twelve trials comparing long acting β2 agonists with placebo, six reported no improvement in exercise capacity, eleven reported improvements in FEV1 lung function (one reported no improvement, six reported less rescue inhaler usage (one reported no difference and five reported improved dyspnea scores (two reported no improvement. Differences in quality of life were detected in one salmeterol trial ; however, two salmeterol, and one formoterol trial reported no differences. Adverse effects of interest were not reported. Conclusion In terms of clinical outcomes and safety, we could not find

  17. Long-acting muscarinic antagonist use in adults with asthma: real-life prescribing and outcomes of add-on therapy with tiotropium bromide

    Directory of Open Access Journals (Sweden)

    Price D

    2015-01-01

    Full Text Available David Price,1,2 Alan Kaplan,3 Rupert Jones,4 Daryl Freeman,5 Anne Burden,2 Shuna Gould,2 Julie von Ziegenweidt,2 Muzammil Ali,2 Christine King,2 Mike Thomas6 1Academic Centre of Primary Care, University of Aberdeen, Aberdeen, 2Research in Real-Life, Cambridge, UK; 3Family Physician Airways Group of Canada, Richmond Hill, ON, Canada; 4Centre for Clinical Trials and Health Research, Plymouth University, Plymouth, 5Norfolk Community Health and Care NHS Trust, Norwich, 6Primary Care Research, University of Southhampton, Southhampton, UK Background: Randomized controlled trials indicate that addition of a long-acting muscarinic antagonist (LAMA such as tiotropium may improve asthma control and reduce exacerbation risk in patients with poorly controlled asthma, but broader clinical studies are needed to investigate the effectiveness of LAMA in real-life asthma care. Methods: Medical records of adults with asthma (aged ≥18 years prescribed tiotropium were obtained from the UK Optimum Patient Care Research Database for the period 2001–2013. Patients diagnosed with chronic obstructive pulmonary disease were excluded, but no other clinical exclusions were applied. Two primary outcomes were compared in the year before (baseline and the year after (outcome addition of tiotropium: exacerbations (asthma-related hospital emergency department attendance or inpatient admission, or acute oral corticosteroid course and acute respiratory events (exacerbation or antibiotic prescription with lower respiratory consultation. Secondary outcomes included lung function test results and short-acting β2 agonist usage. The Wilcoxon signed-rank test was used for variables measured on the interval scale, the marginal homogeneity test for categorized variables, and the paired t-test for lung function indices. Results: Of the 2,042 study patients, 83% were prescribed an inhaled corticosteroid and 68% a long-acting ß2 agonist during the baseline year; 67% were prescribed

  18. Injection-site lesions in carcasses of cattle receiving injections at branding and at weaning.

    Science.gov (United States)

    George, M H; Heinrich, P E; Dexter, D R; Morgan, J B; Odde, K G; Glock, R D; Tatum, J D; Cowman, G L; Smith, G C

    1995-11-01

    Crossbred steer and heifer calves (n = 84) were given injections at branding and at weaning (using a completely randomized block design); 225 to 376 d later, pairs of two subprimal cuts from each animal were evaluated for incidence and severity of injection-site lesions. The four products compared were 1) a 2-mL clostridial, 2) a 5-mL clostridial, 3) vitamin AD3, and 4) a long-acting oxytetracycline antibiotic (OTC). Branding-age calves (mean 48.3 d of age) received intramuscular injections of two of the four products, in the semimembranosus (inside round) muscles (one in the left muscle and one in the right); at weaning age (mean 199.3 d of age), calves received injections of the remaining two products in the gluteus medius (top sirloin butt) muscles (one in the left and the other in the right). Injections at branding of 2 mL of clostridial, 5 mL of clostridial, vitamin AD3, and OTC caused injection-site lesions in 72.5, 92.7, 5.3, and 51.2%, respectively, of inside rounds from slaughter cattle. Incidence of injection-site lesions was lowest (P branding and weaning times) and was highest (P branding or of OT