Evaluation of drug administration errors in a teaching hospital

Directory of Open Access Journals (Sweden)

Berdot Sarah

2012-03-01

Full Text Available Abstract Background Medication errors can occur at any of the three steps of the medication use process: prescribing, dispensing and administration. We aimed to determine the incidence, type and clinical importance of drug administration errors and to identify risk factors. Methods Prospective study based on disguised observation technique in four wards in a teaching hospital in Paris, France (800 beds. A pharmacist accompanied nurses and witnessed the preparation and administration of drugs to all patients during the three drug rounds on each of six days per ward. Main outcomes were number, type and clinical importance of errors and associated risk factors. Drug administration error rate was calculated with and without wrong time errors. Relationship between the occurrence of errors and potential risk factors were investigated using logistic regression models with random effects. Results Twenty-eight nurses caring for 108 patients were observed. Among 1501 opportunities for error, 415 administrations (430 errors with one or more errors were detected (27.6%. There were 312 wrong time errors, ten simultaneously with another type of error, resulting in an error rate without wrong time error of 7.5% (113/1501. The most frequently administered drugs were the cardiovascular drugs (425/1501, 28.3%. The highest risks of error in a drug administration were for dermatological drugs. No potentially life-threatening errors were witnessed and 6% of errors were classified as having a serious or significant impact on patients (mainly omission. In multivariate analysis, the occurrence of errors was associated with drug administration route, drug classification (ATC and the number of patient under the nurse's care. Conclusion Medication administration errors are frequent. The identification of its determinants helps to undertake designed interventions.

[Evaluation of administration errors of injectable drugs in neonatology].

Science.gov (United States)

Cherif, A; Sayadi, M; Ben Hmida, H; Ben Ameur, K; Mestiri, K

2015-11-01

Use of injectable drugs in newborns represents more than 90% of prescriptions and requires special precautions in order to ensure more safety and efficiency. The aim of this study is to gather errors relating to the administration of injectable drugs and to suggest corrective actions. This descriptive and transversal study has evaluated 300 injectable drug administrations in a neonatology unit. Two hundred and sixty-one administrations have contained an error. Data are collected by direct observations of administrative act. Errors observed are: an inappropriate mixture (2.6% of cases); an incorrect delivery rate (33.7% of cases); incorrect dilutions (26.7% of cases); error in calculation of the dose to be injected (16.7% of cases); error while sampling small volumes (6.3% of cases); error or omission of administration schedule (1% of cases). These data have enabled us to evaluate administration of injectable drugs in neonatology. Different types of errors observed could be a source of therapeutic inefficiency, extended lengths of stay or iatrogenic drug. Following these observations, corrective actions have been undertaken by pharmacists and consist of: organizing training sessions for nursing; developing an explanatory guide for dilution and administration of injectable medicines, which was made available to the clinical service. Collaborative strategies doctor-nurse-pharmacist can help to reduce errors in the medication process especially during his administration. It permits improvement of injectable drugs use, offering more security and better efficiency and contribute to guarantee ideal therapy for patients. Copyright © 2015. Published by Elsevier Masson SAS.

Rectal drug administration: clinical pharmacokinetic considerations.

Science.gov (United States)

de Boer, A G; Moolenaar, F; de Leede, L G; Breimer, D D

1982-01-01

The human rectum represents a body cavity in which drugs can be easily introduced and retained and from which absorption is well possible. There are important therapeutic reasons why it is sometimes preferable to give a drug rectally rather than orally, e.g. in cases of nausea and vomiting. Drawbacks of rectal drug administration include the interruption of absorption by defaecation and lack of patient acceptability. The mechanism of drug absorption from the rectum is probably no different to that in the upper part of the gastrointestinal tract, despite the fact that the physiological circumstances (e.g. pH, fluid content) differ substantially, Absorption from aqueous and alcoholic solutions may occur very rapidly, which has proved to be of considerable therapeutic value in the rapid suppression of acute convulsive attacks by diazepam (e.g. in children), but absorption from suppositories is generally slower and very much dependent on the nature of the suppository base, the use of surfactants or other additives, particle size of the active ingredient, etc. There is some evidence that hepatic first-pass elimination of high clearance drugs is partially avoided after rectal administration, e.g. lignocaine. This can be explained by the rectal venous blood supply: the upper part is connected with the portal system, whereas the lower part is directly connected with the systemic circulation. Plasma concentration data following rectal administration of representatives of several classes of drugs are reviewed: anticonvulsants, non-narcotic analgesics and non-steroidal anti-inflammatory agents, hypnosedatives and anaesthetics, strong analgesics, theophylline and derivatives, corticosteroids, antibacterial agents, thiazinamium, promethazine, hyoscine-N-butyl-bromide, streptokinase, progesterone, ergotamine tartrate and levodopa. Only limited number of cases has it been adequately shown that the rectal route of administration gives plasma concentrations which are comparable to

Profile of drug administration errors in anesthesia among anesthesiologists from Santa Catarina

Directory of Open Access Journals (Sweden)

Thomas Rolf Erdmann

2016-02-01

Full Text Available INTRODUCTION: Anesthesiology is the only medical specialty that prescribes, dilutes, and administers drugs without conferral by another professional. Adding to the high frequency of drug administration, a propitious scenario to errors is created. OBJECTIVE: Access the prevalence of drug administration errors during anesthesia among anesthesiologists from Santa Catarina, the circumstances in which they occurred, and possible associated factors. MATERIALS AND METHODS: An electronic questionnaire was sent to all anesthesiologists from Sociedade de Anestesiologia do Estado de Santa Catarina, with direct or multiple choice questions on responder demographics and anesthesia practice profile; prevalence of errors, type and consequence of error; and factors that may have contributed to the errors. RESULTS: Of the respondents, 91.8% reported they had committed administration errors, adding the total error of 274 and mean of 4.7 (6.9 errors per respondent. The most common error was replacement (68.4%, followed by dose error (49.1%, and omission (35%. Only 7% of respondents reported neuraxial administration error. Regarding circumstances of errors, they mainly occurred in the morning (32.7%, in anesthesia maintenance (49%, with 47.8% without harm to the patient and 1.75% with the highest morbidity and irreversible damage, and 87.3% of cases with immediate identification. As for possible contributing factors, the most frequent were distraction and fatigue (64.9% and misreading of labels, ampoules, or syringes (54.4%. CONCLUSION: Most respondents committed more than one error in anesthesia administration, mainly justified as a distraction or fatigue, and of low gravity.

[Innovative therapeutic strategies for intravesical drug administration].

Science.gov (United States)

Moch, C; Salmon, D; Rome, P; Marginean, R; Pivot, C; Colombel, M; Pirot, F

2013-05-01

Perspectives for innovative pharmaceutical molecules and intravesical administration of pharmacological agents are presented in the present review carried out from a recent literature. This review of the literature was built by using the PubMed and ScienceDirect databases running 20keywords revealing 34publications between 1983 and 2012. The number of referenced articles on ScienceDirect has increased in recent years, highlighting the interest of scientists for intravesical drug administration and the relevance of innovating drug delivery systems. Different modalities of intravesical administration using physical (e.g., iontophoresis, electroporation) or chemical techniques (e.g., enzyme, solvent, nanoparticles, liposomes, hydrogels) based on novel formulation methods are reported. Finally, the development of biopharmaceuticals (e.g., bacillus Calmette-Guérin, interferon α) and gene therapies is also presented and analyzed in this review. The present review exhibits new development in the pipeline for emerging intravesical drug administration strategies. Knowledge of all these therapies allows practitioners to propose a specific and tailored treatment to each patient with limiting systemic side effects. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

MODELING OF TARGETED DRUG DELIVERY PART II. MULTIPLE DRUG ADMINISTRATION

Directory of Open Access Journals (Sweden)

A. V. Zaborovskiy

2017-01-01

Full Text Available In oncology practice, despite significant advances in early cancer detection, surgery, radiotherapy, laser therapy, targeted therapy, etc., chemotherapy is unlikely to lose its relevance in the near future. In this context, the development of new antitumor agents is one of the most important problems of cancer research. In spite of the importance of searching for new compounds with antitumor activity, the possibilities of the “old” agents have not been fully exhausted. Targeted delivery of antitumor agents can give them a “second life”. When developing new targeted drugs and their further introduction into clinical practice, the change in their pharmacodynamics and pharmacokinetics plays a special role. The paper describes a pharmacokinetic model of the targeted drug delivery. The conditions under which it is meaningful to search for a delivery vehicle for the active substance were described. Primary screening of antitumor agents was undertaken to modify them for the targeted delivery based on underlying assumptions of the model.

38 CFR 52.180 - Administration of drugs.

Science.gov (United States)

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Administration of drugs... of drugs. The program management must assist with the management of medication and have a system for disseminating drug information to participants and program staff. (a) Procedures. (1) The program management...

Pharmacokinetics of sulfamethoxazole and trimethoprim in Pacific white shrimp, Litopenaeus vannamei, after oral administration of single-dose and multiple-dose.

Science.gov (United States)

Ma, Rongrong; Wang, Yuan; Zou, Xiong; Hu, Kun; Sun, Beibei; Fang, Wenhong; Fu, Guihong; Yang, Xianle

2017-06-01

The tissue distribution and depletion of sulfamethoxazole (SMZ) and trimethoprim (TMP) were studied in Pacific white shrimp, Litopenaeus vannamei, after single-dose and multiple-dose oral administration of SMZ-TMP (5:1) via medicated feed. In single-dose oral administration, shrimps were fed once at a dose of 100 mg/kg (drug weight/body weight). In multiple-dose oral administration, shrimps were fed three times a day for three consecutive days at a dose of 100mg/kg. The results showed the kinetic characteristic of SMZ was different from TMP in Pacific white shrimp. In the single-dose administration, the SMZ was widely distributed in the tissues, while TMP was highly concentrated in the hepatopancreas. The t 1/2z values of SMZ were larger and persist longer than TMP in Pacific white shrimp. In the multiple-dose administration, SMZ accumulated well in the tissues, and reached steady state level after successive administrations, while TMP did not. TMP concentration even appeared the downward trend with the increase of drug times. Compared with the single dose, the t 1/2z values of SMZ in hepatopancreas (8.22-11.33h) and muscle (6.53-10.92h) of Pacific white shrimps rose, but the haemolymph dropped (13.76-11.03) in the multiple-dose oral administration. Meanwhile, the corresponding values of TMP also rose in hepatopancreas (4.53-9.65h) and muscle (2.12-2.71h), and declined in haemolymph (7.38-5.25h) following single-dose and multiple-dose oral administration in Pacific white shrimps. In addition, it is worth mentioning that the ratios of SMZ and TMP were unusually larger than the general aim ratio. Copyright © 2017 Elsevier B.V. All rights reserved.

75 FR 15439 - Food and Drug Administration/Xavier University Global Medical Device Conference

Science.gov (United States)

2010-03-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Food and Drug Administration/Xavier University Global Medical Device Conference AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public conference. SUMMARY: The Food and Drug Administration (FDA...

78 FR 15957 - Food and Drug Administration/Xavier University Global Medical Device Conference

Science.gov (United States)

2013-03-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Food and Drug Administration/Xavier University Global Medical Device Conference AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public conference. SUMMARY: The Food and Drug Administration (FDA...

77 FR 10537 - Food and Drug Administration/Xavier University Global Medical Device Conference

Science.gov (United States)

2012-02-22

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Food and Drug Administration/Xavier University Global Medical Device Conference AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public conference. SUMMARY: The Food and Drug Administration (FDA...

Evaluation of drug administration errors in a teaching hospital

OpenAIRE

Berdot, Sarah; Sabatier, Brigitte; Gillaizeau, Florence; Caruba, Thibaut; Prognon, Patrice; Durieux, Pierre

2012-01-01

Abstract Background Medication errors can occur at any of the three steps of the medication use process: prescribing, dispensing and administration. We aimed to determine the incidence, type and clinical importance of drug administration errors and to identify risk factors. Methods Prospective study based on disguised observation technique in four wards in a teaching hospital in Paris, France (800 beds). A pharmacist accompanied nurses and witnessed the preparation and administration of drugs...

Food and Drug Administration Drug Approval Process: A History and Overview.

Science.gov (United States)

Williams, Christopher Ty

2016-03-01

In this article, the processing of investigational and new drug applications is described and the standard and expedited review processes are examined. The efforts of the US Food and Drug Administration to ensure greater agency transparency and fiscal responsibility and intensify oversight during the drug development and approval process are reviewed. Often attributed to a decrease in the number of uninsured adults, both the increase in prescription drug sales and the high costs associated with bringing a new drug to market highlight the necessity for a streamlined and cost-effective process to deliver these drugs safely and effectively. Copyright © 2016 Elsevier Inc. All rights reserved.

Discrete-choice modelling of patient preferences for modes of drug administration.

Science.gov (United States)

Tetteh, Ebenezer Kwabena; Morris, Steve; Titcheneker-Hooker, Nigel

2017-12-01

The administration of (biologically-derived) drugs for various disease conditions involves consumption of resources that constitutes a direct monetary cost to healthcare payers and providers. An often ignored cost relates to a mismatch between patients' preferences and the mode of drug administration. The "intangible" benefits of giving patients what they want in terms of the mode of drug delivery is seldom considered. This study aims to evaluate, in monetary terms, end-user preferences for the non-monetary attributes of different modes of drug administration using a discrete-choice experiment. It provides empirical support to the notion that there are significant benefits from developing patient-friendly approaches to drug delivery. The gross benefits per patient per unit administration is in the same order of magnitude as the savings in resource costs of administering drugs. The study argues that, as long as the underlying manufacturing science is capable, a patient-centred approach to producing drug delivery systems should be encouraged and pursued.

Pharmacokinetics of guaifenesin following administration of multiple doses to exercised Thoroughbred horses.

Science.gov (United States)

Knych, H K; Stanley, S D; Benson, D; Arthur, R M

2016-08-01

Guaifenesin is an expectorant commonly used in performance horses to aid in the clearance of mucus from the airways. Guaifenesin is also a centrally acting skeletal muscle relaxant and as such is a prohibited drug with withdrawal necessary prior to competition. To the authors' knowledge, there are no reports in the literature describing single or multiple oral administrations of guaifenesin in the horse to determine a regulatory threshold and related withdrawal time. Therefore, the objective of the current study was to describe the pharmacokinetics of guaifenesin following oral administration in order to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 2 g of guaifenesin orally BID for a total of five doses. Blood samples were collected immediately prior to drug administration and at various times postadministration. Serum guaifenesin concentrations were determined and pharmacokinetic parameters calculated. Guaifenesin was rapidly absorbed (Tmax of 15 min) following oral administration. The Cmax was 681.3 ± 323.8 ng/mL and 1080 ± 732.8 following the first and last dose, respectively. The serum elimination half-life was 2.62 ± 1.24 h. Average serum guaifenesin concentrations remained above the LOQ of the assay (0.5 ng/mL) by 48 h postadministration of the final dose in 3 of 9 horses. © 2016 John Wiley & Sons Ltd.

21 CFR 20.2 - Production of records by Food and Drug Administration employees.

Science.gov (United States)

2010-04-01

... upon an officer or employee of the Food and Drug Administration commanding the production of any record... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Production of records by Food and Drug Administration employees. 20.2 Section 20.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...

Enrichment Strategies in Pediatric Drug Development: An Analysis of Trials Submitted to the US Food and Drug Administration.

Science.gov (United States)

Green, Dionna J; Liu, Xiaomei I; Hua, Tianyi; Burnham, Janelle M; Schuck, Robert; Pacanowski, Michael; Yao, Lynne; McCune, Susan K; Burckart, Gilbert J; Zineh, Issam

2017-12-08

Clinical trial enrichment involves prospectively incorporating trial design elements that increase the probability of detecting a treatment effect. The use of enrichment strategies in pediatric drug development has not been systematically assessed. We analyzed the use of enrichment strategies in pediatric trials submitted to the US Food and Drug Administration from 2012-2016. In all, 112 efficacy studies associated with 76 drug development programs were assessed and their overall success rates were 78% and 75%, respectively. Eighty-eight trials (76.8%) employed at least one enrichment strategy; of these, 66.3% employed multiple enrichment strategies. The highest trial success rates were achieved when all three enrichment strategies (practical, predictive, and prognostic) were used together within a single trial (87.5%), while the lowest success rate was observed when no enrichment strategy was used (65.4%). The use of enrichment strategies in pediatric trials was found to be associated with trial and program success in our analysis. © 2017 American Society for Clinical Pharmacology and Therapeutics.

A System for Anesthesia Drug Administration Using Barcode Technology: The Codonics Safe Label System and Smart Anesthesia Manager.

Science.gov (United States)

Jelacic, Srdjan; Bowdle, Andrew; Nair, Bala G; Kusulos, Dolly; Bower, Lynnette; Togashi, Kei

2015-08-01

Many anesthetic drug errors result from vial or syringe swaps. Scanning the barcodes on vials before drug preparation, creating syringe labels that include barcodes, and scanning the syringe label barcodes before drug administration may help to prevent errors. In contrast, making syringe labels by hand that comply with the recommendations of regulatory agencies and standards-setting bodies is tedious and time consuming. A computerized system that uses vial barcodes and generates barcoded syringe labels could address both safety issues and labeling recommendations. We measured compliance of syringe labels in multiple operating rooms (ORs) with the recommendations of regulatory agencies and standards-setting bodies before and after the introduction of the Codonics Safe Label System (SLS). The Codonics SLS was then combined with Smart Anesthesia Manager software to create an anesthesia barcode drug administration system, which allowed us to measure the rate of scanning syringe label barcodes at the time of drug administration in 2 cardiothoracic ORs before and after introducing a coffee card incentive. Twelve attending cardiothoracic anesthesiologists and the OR satellite pharmacy participated. The use of the Codonics SLS drug labeling system resulted in >75% compliant syringe labels (95% confidence interval, 75%-98%). All syringe labels made using the Codonics SLS system were compliant. The average rate of scanning barcodes on syringe labels using Smart Anesthesia Manager was 25% (730 of 2976) over 13 weeks but increased to 58% (956 of 1645) over 8 weeks after introduction of a simple (coffee card) incentive (P < 0.001). An anesthesia barcode drug administration system resulted in a moderate rate of scanning syringe label barcodes at the time of drug administration. Further, adaptation of the system will be required to achieve a higher utilization rate.

Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992; policies, requirements, and administrative procedures; delay of effective date; reopening of administrative record. Food and Drug Administration, HHS. Final rule; delay of effective date; reopening of administrative record.

Science.gov (United States)

2000-05-03

The Food and Drug Administration (FDA) is delaying until October 1, 2001, the effective date and reopening the administrative record to receive additional comments regarding certain requirements of a final rule published in the Federal Register of December 3, 1999 (64 FR 67720). The other provisions of the final rule become effective on December 4, 2000. The final rule implements the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA) and the FDA Modernization Act of 1997 (the Modernization Act). FDA is delaying the effective date for certain requirements relating to wholesale distribution of prescription drugs by distributors that are not authorized distributors of record. FDA is also delaying the effective date of another requirement that would prohibit blood centers functioning as "health care entities" to act as wholesale distributors of blood derivatives. The agency is taking this action to address numerous concerns about the provisions raised by affected parties.

Accuracy of manual entry of drug administration data into an anesthesia information management system.

Science.gov (United States)

Avidan, Alexander; Dotan, Koren; Weissman, Charles; Cohen, Matan J; Levin, Phillip D

2014-11-01

Data on drug administration are entered manually into anesthesia information management systems (AIMS). This study examined whether these data are accurate regarding drug name, dose administered, and time of administration, and whether the stage of anesthesia influences data accuracy. Real-time observational data on drug administration during elective operations were compared with computerized information on drug administration entered by anesthesiologists. A trained observer (K.D.) performed the observations. Data were collected during 57 operations which included 596 separate occasions of drug administration by 22 anesthesiologists. No AIMS records were found for 90 (15.1%) occasions of drug administration (omissions), while there were 11 (1.8%) AIMS records where drug administration was not observed. The AIMS and observer data matched for drug name on 495 of 596 (83.1%) occasions, for dose on 439 of 495 (92.5%) occasions, and for time on 476 of 495 (96.2%) occasions. Amongst the 90 omitted records, 34 (37.8%) were for vasoactive drugs with 24 (27.7%) for small doses of hypnotics. Omissions occurred mostly during maintenance: 50 of 153 (24.6%), followed by induction: 30 of 325 (9.2%) and emergence: 10 of 57 (17.5%) (P < 0.001). Time and dose inaccuracies occurred mainly during induction, followed by maintenance and emergence; time inaccuracies were 7/325 (8.3%), 10/203 (4.9%), and 0/57 (0%), respectively (P = 0.07), and dose inaccuracies were 15/325 (4.6%), 3/203 (1.5%), and 1/57 (1.7%), respectively (P = 0.11). The range of accuracy varies when anesthesiologists manually enter drug administration data into an AIMS. Charting omissions represent the largest cause of inaccuracy, principally by omissions of records for vasopressors and small doses of hypnotic drugs. Manually entered drug administration data are not without errors. Accuracy of entering drug administration data remains the responsibility of the anesthesiologist.

75 FR 22412 - Food and Drug Administration/Xavier University Global Outsourcing Conference

Science.gov (United States)

2010-04-28

... Selection Process--the criteria a contract organization should use to consider saying no to a contract... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Food and Drug Administration/Xavier University Global Outsourcing Conference AGENCY: Food and Drug...

Hierarchical pulmonary target nanoparticles via inhaled administration for anticancer drug delivery.

Science.gov (United States)

Chen, Rui; Xu, Liu; Fan, Qin; Li, Man; Wang, Jingjing; Wu, Li; Li, Weidong; Duan, Jinao; Chen, Zhipeng

2017-11-01

Inhalation administration, compared with intravenous administration, significantly enhances chemotherapeutic drug exposure to the lung tissue and may increase the therapeutic effect for pulmonary anticancer. However, further identification of cancer cells after lung deposition of inhaled drugs is necessary to avoid side effects on normal lung tissue and to maximize drug efficacy. Moreover, as the action site of the major drug was intracellular organelles, drug target to the specific organelle is the final key for accurate drug delivery. Here, we designed a novel multifunctional nanoparticles (MNPs) for pulmonary antitumor and the material was well-designed for hierarchical target involved lung tissue target, cancer cell target, and mitochondrial target. The biodistribution in vivo determined by UHPLC-MS/MS method was employed to verify the drug concentration overwhelmingly increasing in lung tissue through inhaled administration compared with intravenous administration. Cellular uptake assay using A549 cells proved the efficient receptor-mediated cell endocytosis. Confocal laser scanning microscopy observation showed the location of MNPs in cells was mitochondria. All results confirmed the intelligent material can progressively play hierarchical target functions, which could induce more cell apoptosis related to mitochondrial damage. It provides a smart and efficient nanocarrier platform for hierarchical targeting of pulmonary anticancer drug. So far, this kind of material for pulmonary mitochondrial-target has not been seen in other reports.

21 CFR 20.120 - Records available in Food and Drug Administration Public Reading Rooms.

Science.gov (United States)

2010-04-01

... Public Reading Rooms. 20.120 Section 20.120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF....120 Records available in Food and Drug Administration Public Reading Rooms. (a) The Food and Drug Administration operates two public reading rooms. The Freedom of Information Staff's Public Reading Room is...

Systematic review of drug administration costs and implications for biopharmaceutical manufacturing.

Science.gov (United States)

Tetteh, Ebenezer; Morris, Stephen

2013-10-01

The acquisition costs of biologic drugs are often considered to be relatively high compared with those of nonbiologics. However, the total costs of delivering these drugs also depend on the cost of administration. Ignoring drug administration costs may distort resource allocation decisions because these affect cost effectiveness. The objectives of this systematic review were to develop a framework of drug administration costs that considers both the costs of physical administration and the associated proximal costs; and, as a case example, to use this framework to evaluate administration costs for biologics within the UK National Health Service (NHS). We reviewed literature that reported estimates of administration costs for biologics within the UK NHS to identify how these costs were quantified and to examine how differences in dosage forms and regimens influenced administration costs. The literature reviewed were identified by searching the Centre for Review and Dissemination Databases (DARE, NHS EED and HTA); EMBASE (The Excerpta Medica Database); MEDLINE (using the OVID interface); Econlit (EBSCO); Tufts Medical Center Cost Effectiveness Analysis (CEA) Registry; and Google Scholar. We identified 4,344 potentially relevant studies, of which 43 studies were selected for this systematic review. We extracted estimates of the administration costs of biologics from these studies. We found evidence of variation in the way that administration costs were measured, and that this affected the magnitude of costs reported, which could then influence cost effectiveness. Our findings suggested that manufacturers of biologic medicines should pay attention to formulation issues and their impact on administration costs, because these affect the total costs of healthcare delivery and cost effectiveness.

27 CFR 17.136 - Compliance with Food and Drug Administration requirements.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Compliance with Food and Drug Administration requirements. 17.136 Section 17.136 Alcohol, Tobacco Products and Firearms ALCOHOL... Compliance with Food and Drug Administration requirements. A product is not a medicine, medicinal preparation...

Vegetable Oil-Loaded Nanocapsules: Innovative Alternative for Incorporating Drugs for Parenteral Administration.

Science.gov (United States)

Venturinil, C G; Bruinsmann, A; Oliveira, C P; Contri, R V; Pohlmann, A R; Guterres, S S

2016-02-01

An innovative nanocapsule formulation for parenteral administration using selected vegetable oils (mango, jojoba, pequi, oat, annatto, calendula, and chamomile) was developed that has the potential to encapsulate various drugs. The vegetable oil-loaded nanocapsules were prepared by interfacial deposition and compared with capric/caprylic triglyceride-loaded lipid core nanocapsules. The major objective was to investigate the effect of vegetable oils on particle size distribution and physical stability and to determine the hemolytic potential of the nanocapsules, considering their applicability for intravenous administration. Taking into account the importance of accurately determining particle size for the selected route of administration, different size characterization techniques were employed, such as Laser Diffraction, Dynamic Light Scattering, Multiple Light Scattering, Nanoparticle Tracking Analysis, and Transmission Electronic Microscopy. Laser diffraction studies indicated that the mean particle size of all nanocapsules was below 300 nm. For smaller particles, the laser diffraction and multiple light scattering data were in agreement (D[3,2]-130 nm). Dynamic light scattering and nanoparticle tracking analysis, two powerful techniques that complement each other, exhibited size values between 180 and 259 nm for all nanoparticles. Stability studies demonstrated a tendency of particle creaming for jojoba-nanocapsules and sedimentation for the other nanoparticles; however, no size variation occurred over 30 days. The hemolysis test proved the hemocompatibility of all nanosystems, irrespective of the type of oil. Although all developed nanocapsules presented the potential for parenteral administration, jojoba oil-loaded nanocapsules were selected as the most promising nanoformulation due to their low average size and high particle size homogeneity.

Common errors of drug administration in infants: causes and avoidance.

Science.gov (United States)

Anderson, B J; Ellis, J F

1999-01-01

Drug administration errors are common in infants. Although the infant population has a high exposure to drugs, there are few data concerning pharmacokinetics or pharmacodynamics, or the influence of paediatric diseases on these processes. Children remain therapeutic orphans. Formulations are often suitable only for adults; in addition, the lack of maturation of drug elimination processes, alteration of body composition and influence of size render the calculation of drug doses complex in infants. The commonest drug administration error in infants is one of dose, and the commonest hospital site for this error is the intensive care unit. Drug errors are a consequence of system error, and preventive strategies are possible through system analysis. The goal of a zero drug error rate should be aggressively sought, with systems in place that aim to eliminate the effects of inevitable human error. This involves review of the entire system from drug manufacture to drug administration. The nuclear industry, telecommunications and air traffic control services all practise error reduction policies with zero error as a clear goal, not by finding fault in the individual, but by identifying faults in the system and building into that system mechanisms for picking up faults before they occur. Such policies could be adapted to medicine using interventions both specific (the production of formulations which are for children only and clearly labelled, regular audit by pharmacists, legible prescriptions, standardised dose tables) and general (paediatric drug trials, education programmes, nonpunitive error reporting) to reduce the number of errors made in giving medication to infants.

21 CFR 20.3 - Certification and authentication of Food and Drug Administration records.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Certification and authentication of Food and Drug... authentication of Food and Drug Administration records. (a) Upon request, the Food and Drug Administration will... or for authentication of records shall be sent in writing to the Freedom of Information Staff (HFI-35...

78 FR 30317 - Science Board to the Food and Drug Administration; Notice of Meeting

Science.gov (United States)

2013-05-22

... 24, 2013, from approximately 1 p.m. to 3:45 p.m. Location: Food and Drug Administration, White Oak..., Office of the Chief Scientist, Office of the Commissioner, Food and Drug Administration, White Oak Bldg... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001...

76 FR 61366 - Food and Drug Administration Transparency Initiative: Draft Proposals for Public Comment to...

Science.gov (United States)

2011-10-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0247] Food and Drug Administration Transparency Initiative: Draft Proposals for Public Comment to Increase...: Food and Drug Administration, HHS. [[Page 61367

77 FR 11553 - Draft Guidance on Food and Drug Administration Oversight of Positron Emission Tomography Drug...

Science.gov (United States)

2012-02-27

... Oversight of PET Drug Products--Questions and Answers.'' The draft guidance provides questions and answers... assist that office in processing your requests. See the SUPPLEMENTARY INFORMATION section for electronic... PET Drug Products--Questions and Answers.'' In 1997, Congress passed the Food and Drug Administration...

Pharmacokinetics of voriconazole after oral administration of single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis).

Science.gov (United States)

Sanchez-Migallon Guzman, David; Flammer, Keven; Papich, Mark G; Grooters, Amy M; Shaw, Shannon; Applegate, Jeff; Tully, Thomas N

2010-04-01

To determine the pharmacokinetics and safety of voriconazole administered orally in single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis). 15 clinically normal adult Hispaniolan Amazon parrots. Single doses of voriconazole (12 or 24 mg/kg) were administered orally to 15 and 12 birds, respectively; plasma voriconazole concentrations were determined at intervals via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) or water was administered orally to 6 and 4 birds, respectively, every 8 hours for 11 days (beginning day 0); trough plasma voriconazole concentrations were evaluated on 3 days. Birds were monitored daily, and clinicopathologic variables were evaluated before and after the trial. Voriconazole elimination half-life was short (0.70 to 1.25 hours). In the single-dose experiments, higher drug doses yielded proportional increases in the maximum plasma voriconazole concentration (C(max)) and area under the curve (AUC). In the multiple-dose trial, C(max), AUC, and plasma concentrations at 2 and 4 hours were decreased on day 10, compared with day 0 values; however, there was relatively little change in terminal half-life. With the exception of 1 voriconazole-treated parrot that developed polyuria, adverse effects were not evident. In Hispaniolan Amazon parrots, oral administration of voriconazole was associated with proportional kinetics following administration of single doses and a decrease in plasma concentration following administration of multiple doses. Oral administration of 18 mg of voriconazole/kg every 8 hours would require adjustment to maintain therapeutic concentrations during long-term treatment. Safety and efficacy of voriconazole treatment in this species require further investigation.

78 FR 14557 - Guidance for Industry and Food and Drug Administration Staff: Investigational Device Exemption...

Science.gov (United States)

2013-03-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-D-0010] Guidance for Industry and Food and Drug Administration Staff: Investigational Device Exemption Guidance for Retinal Prostheses; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The...

Adverse Drug Events caused by Serious Medication Administration Errors

Science.gov (United States)

Sawarkar, Abhivyakti; Keohane, Carol A.; Maviglia, Saverio; Gandhi, Tejal K; Poon, Eric G

2013-01-01

OBJECTIVE To determine how often serious or life-threatening medication administration errors with the potential to cause patient harm (or potential adverse drug events) result in actual patient harm (or adverse drug events (ADEs)) in the hospital setting. DESIGN Retrospective chart review of clinical events that transpired following observed medication administration errors. BACKGROUND Medication errors are common at the medication administration stage for hospitalized patients. While many of these errors are considered capable of causing patient harm, it is not clear how often patients are actually harmed by these errors. METHODS In a previous study where 14,041 medication administrations in an acute-care hospital were directly observed, investigators discovered 1271 medication administration errors, of which 133 had the potential to cause serious or life-threatening harm to patients and were considered serious or life-threatening potential ADEs. In the current study, clinical reviewers conducted detailed chart reviews of cases where a serious or life-threatening potential ADE occurred to determine if an actual ADE developed following the potential ADE. Reviewers further assessed the severity of the ADE and attribution to the administration error. RESULTS Ten (7.5% [95% C.I. 6.98, 8.01]) actual adverse drug events or ADEs resulted from the 133 serious and life-threatening potential ADEs, of which 6 resulted in significant, three in serious, and one life threatening injury. Therefore 4 (3% [95% C.I. 2.12, 3.6]) serious and life threatening potential ADEs led to serious or life threatening ADEs. Half of the ten actual ADEs were caused by dosage or monitoring errors for anti-hypertensives. The life threatening ADE was caused by an error that was both a transcription and a timing error. CONCLUSION Potential ADEs at the medication administration stage can cause serious patient harm. Given previous estimates of serious or life-threatening potential ADE of 1.33 per 100

Adverse Drug Reactions Related to Drug Administration in Hospitalized Patients.

Science.gov (United States)

Gallelli, Luca; Siniscalchi, Antonio; Palleria, Caterina; Mumoli, Laura; Staltari, Orietta; Squillace, Aida; Maida, Francesca; Russo, Emilio; Gratteri, Santo; De Sarro, Giovambattista

2017-01-01

Drug treatment may be related to the development of adverse drug reactions (ADRs). In this paper, we evaluated the ADRs in patients admitted to Catanzaro Hospital. After we obtained the approval by local Ethical Committee, we performed a retrospective study on clinical records from March 01, 2013 to April 30, 2015. The association between drug and ADR or between drug and drug-drug-interactions (DDIs) was evaluated using the Naranjo's probability scale and Drug Interaction Probability Scale (DIPS), respectively. During the study period, we analyzed 2870 clinical records containing a total of 11,138 prescriptions, and we documented the development of 770 ADRs. The time of hospitalization was significantly higher (P<0.05) in women with ADRs (12.6 ± 1.2 days) with respect to men (11.8± 0.83 days). Using the Naranjo score, we documented a probable association in 78% of these reactions, while DIPS revealed that about 22% of ADRs were related to DDIs. Patients with ADRs received 3052 prescriptions on 11,138 (27.4%) having a mean of 6.1±0.29 drugs that was significantly higher (P<0.01) with respect to patients not experiencing ADRs (mean of 3.4±0.13 drugs). About 19% of ADRs were not diagnosed and were treated as new diseases. Our results indicate that drug administration induces the development of ADRs also during the hospitalization, particularly in elderly women. Moreover, we also documented that ADRs in some patients are under-diagnosed, therefore, it is important to motivate healthcare to report the ADRs in order to optimize the patients' safety. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

76 FR 28046 - Memorandum of Understanding Between the Food and Drug Administration and the International...

Science.gov (United States)

2011-05-13

... Tots Public-Private Partnership AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0005; FDA 225-09-0014] Memorandum of Understanding Between the Food and Drug Administration and the...

78 FR 20666 - Food and Drug Administration/National Institutes of Health/National Science Foundation Public...

Science.gov (United States)

2013-04-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0345] Food and Drug Administration/National Institutes of Health/ National Science Foundation Public Workshop... public workshop; request for comments. SUMMARY: The Food and Drug Administration (FDA) is announcing its...

76 FR 43689 - Draft Guidance for Industry and Food and Drug Administration Staff; Mobile Medical Applications...

Science.gov (United States)

2011-07-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0530] Draft Guidance for Industry and Food and Drug Administration Staff; Mobile Medical Applications; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...

78 FR 277 - Food and Drug Administration Actions Related to Nicotine Replacement Therapies and Smoking...

Science.gov (United States)

2013-01-03

... Dependence; Public Hearing; Extension of Comment Period AGENCY: Food and Drug Administration, HHS. ACTION: Notification of public hearing; Extension of comment period. SUMMARY: The Food and Drug Administration (FDA) is... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 15 [Docket No...

78 FR 15370 - Draft Guidance for Industry and Food and Drug Administration Staff: Recommendations for Labeling...

Science.gov (United States)

2013-03-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-0168] Draft Guidance for Industry and Food and Drug Administration Staff: Recommendations for Labeling Medical...; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...

Comparison of drug treatment histories of single and multiple drug abusers in detox.

Science.gov (United States)

Greberman, S B; Jasinski, D

2001-01-01

This study was undertaken to determine differences in previous treatment patterns in individuals currently using different numbers of substances. Medical records of 1198 inpatient detoxification (detox) admissions were analyzed. Numbers of past admissions to completed detox, methadone, or other types of drug abuse treatment were totaled and ranked to determine most frequent type. Within gender, treatment histories of single and multiple drug abusers usually do not differ. The one exception is male multiple drug abusers ages 26-30, who show increased admissions. Possible explanations are that men do not seek treatment before developing medical complications of addiction or until external factors influence admission. There were differences in treatment histories between genders in multiple drug abusers only. Before age 30, women reported increased treatment of certain types. Possible explanations are that treatment priority is given to women who are, or may be, pregnant. Also, younger men may not enter or complete treatment. Previous treatment history may influence many behaviors. The results of this study delineate several valuable indicators for assessing past history.

78 FR 21085 - Establishment of a Public Docket for Administrative Detention Under the Food and Drug...

Science.gov (United States)

2013-04-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Chapter I [Docket No. FDA-2013-N-0365] Establishment of a Public Docket for Administrative Detention Under the Food and Drug Administration Safety and Innovation Act AGENCY: Food and Drug Administration, HHS. ACTION: Establishment of...

75 FR 70271 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Science.gov (United States)

2010-11-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0515] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

76 FR 9027 - Draft Guidance for Industry and Food and Drug Administration Staff on Best Practices for...

Science.gov (United States)

2011-02-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0057] Draft Guidance for Industry and Food and Drug Administration Staff on Best Practices for Conducting and...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

Role of mass drug administration in elimination of Plasmodium falciparum malaria: a consensus modelling study.

Science.gov (United States)

Brady, Oliver J; Slater, Hannah C; Pemberton-Ross, Peter; Wenger, Edward; Maude, Richard J; Ghani, Azra C; Penny, Melissa A; Gerardin, Jaline; White, Lisa J; Chitnis, Nakul; Aguas, Ricardo; Hay, Simon I; Smith, David L; Stuckey, Erin M; Okiro, Emelda A; Smith, Thomas A; Okell, Lucy C

2017-07-01

Mass drug administration for elimination of Plasmodium falciparum malaria is recommended by WHO in some settings. We used consensus modelling to understand how to optimise the effects of mass drug administration in areas with low malaria transmission. We collaborated with researchers doing field trials to establish a standard intervention scenario and standard transmission setting, and we input these parameters into four previously published models. We then varied the number of rounds of mass drug administration, coverage, duration, timing, importation of infection, and pre-administration transmission levels. The outcome of interest was the percentage reduction in annual mean prevalence of P falciparum parasite rate as measured by PCR in the third year after the final round of mass drug administration. The models predicted differing magnitude of the effects of mass drug administration, but consensus answers were reached for several factors. Mass drug administration was predicted to reduce transmission over a longer timescale than accounted for by the prophylactic effect alone. Percentage reduction in transmission was predicted to be higher and last longer at lower baseline transmission levels. Reduction in transmission resulting from mass drug administration was predicted to be temporary, and in the absence of scale-up of other interventions, such as vector control, transmission would return to pre-administration levels. The proportion of the population treated in a year was a key determinant of simulated effectiveness, irrespective of whether people are treated through high coverage in a single round or new individuals are reached by implementation of several rounds. Mass drug administration was predicted to be more effective if continued over 2 years rather than 1 year, and if done at the time of year when transmission is lowest. Mass drug administration has the potential to reduce transmission for a limited time, but is not an effective replacement for existing

28 CFR 0.138 - Federal Bureau of Investigation, Drug Enforcement Administration, Bureau of Alcohol, Tobacco...

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Federal Bureau of Investigation, Drug Enforcement Administration, Bureau of Alcohol, Tobacco, Firearms, and Explosives, Bureau of Prisons, Federal... Administrative Matters § 0.138 Federal Bureau of Investigation, Drug Enforcement Administration, Bureau of...

[Treatment of Chemotherapy Related Leukocytopenia by Oral Administration of Multiple Leucogenic Drugs Combined with G-CSF: an Experimental Study].

Science.gov (United States)

Zhang, Xi-ping; Zhang, Xiang; Yang, Hong-jian; Zou, De-hong; He, Xiang-ming; Yu, Xing-fei; Li, Yong-feng

2015-07-01

To evaluate efficacies of three commonly used oral drugs including Berbamine Hydrochloride Tablet (B), Qijiao Shengbai Capsule (Q), and Leucogen Tablet (L) (by single drug, two drugs or three drugs) combined with granulocyte colony-stimulating factor (G-CSF) for treat ment of chemotherapy related leukocytopenia in mice. Totally 156 Kunming male mice were divided into the normal control group (A, n=24), the model group (B, n=24), the G-CSF group (C, n =24), the G-CSF+Q group (D, n=12), G-CSF+ B (E, n=12), the G-CSF+L group (F, n=12), the G-CSF + Q + B group (G, n=12), the G-CSF + Q + L group (H, n=12), the G-CSF + L + B group (I, n=12), and the G-CSF + L + Q + B (J, n=12). Mouse models of chemotherapy related leukocytopenia were established by intraperitoneal injection of cyclophosphamide (CTX). A G-CSF group was set up as a positive control. Mice were treated by a single oral drug, a single oral drug combined with G-CSF, and two or three drugs combined with G-CSF respectively, and the death rate calculated. Hemocytes [such as white blood cells (WBC) and its classification, red blood cells (RBC), platelet (PLT), hemoglobin (Hb)] were calculated by hematology analyzer. Mice were anatomized and important organs weighed. Organ indices were calculated. There was no statistical difference in the mortality rate among all groups (P > 0.05). Compared with Group B, WBC was elevated in all other groups (P drug B and L (P chemotherapy related leukopenia or decreased three blood series was to administrate three commonly oral drugs combined with G-CSF. Authors speculated that G-CSF and Q might have a certain effect on CTX induced immune inhibition.

75 FR 17143 - Draft Guidance for Industry and Food and Drug Administration Staff; Medical Devices; Neurological...

Science.gov (United States)

2010-04-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-D-0495] Draft Guidance for Industry and Food and Drug Administration Staff; Medical Devices; Neurological and Physical Medicine Device Guidance Documents; Availability AGENCY: Food and Drug Administration, HHS. ACTION...

76 FR 789 - Guidance for Industry and Food and Drug Administration Staff; Section 905(j) Reports...

Science.gov (United States)

2011-01-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0635] Guidance for Industry and Food and Drug Administration Staff; Section 905(j) Reports: Demonstrating Substantial Equivalence for Tobacco Products; Availability AGENCY: Food and Drug Administration, HHS. ACTION...

76 FR 50740 - Draft Guidance for Industry and Food and Drug Administration Staff; Procedures for Handling...

Science.gov (United States)

2011-08-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0514] Draft Guidance for Industry and Food and Drug Administration Staff; Procedures for Handling Section 522 Postmarket Surveillance Studies; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice...

75 FR 47603 - Draft Guidance for Industry and Food and Drug Administration Staff; Recommendations for Premarket...

Science.gov (United States)

2010-08-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0395] Draft Guidance for Industry and Food and Drug Administration Staff; Recommendations for Premarket Notifications for Lamotrigine and Zonisamide Assays; Availability AGENCY: Food and Drug Administration, HHS...

Expand classical drug administration ways by emerging routes using dendrimer drug delivery systems: a concise overview.

Science.gov (United States)

Mignani, Serge; El Kazzouli, Saïd; Bousmina, Mosto; Majoral, Jean-Pierre

2013-10-01

Drugs are introduced into the body by numerous routes such as enteral (oral, sublingual and rectum administration), parenteral (intravascular, intramuscular, subcutaneous and inhalation administration), or topical (skin and mucosal membranes). Each route has specific purposes, advantages and disadvantages. Today, the oral route remains the preferred one for different reasons such as ease and compliance by patients. Several nanoformulated drugs have been already approved by the FDA, such as Abelcet®, Doxil®, Abraxane® or Vivagel®(Starpharma) which is an anionic G4-poly(L-lysine)-type dendrimer showing potent topical vaginal microbicide activity. Numerous biochemical studies, as well as biological and pharmacological applications of both dendrimer based products (dendrimers as therapeutic compounds per se, like Vivagel®) and dendrimers as drug carriers (covalent conjugation or noncovalent encapsulation of drugs) were described. It is widely known that due to their outstanding physical and chemical properties, dendrimers afforded improvement of corresponding carried-drugs as dendrimer-drug complexes or conjugates (versus plain drug) such as biodistribution and pharmacokinetic behaviors. The purpose of this manuscript is to review the recent progresses of dendrimers as nanoscale drug delivery systems for the delivery of drugs using enteral, parenteral and topical routes. In particular, we focus our attention on the emerging and promising routes such as oral, transdermal, ocular and transmucosal routes using dendrimers as delivery systems. Copyright © 2013 Elsevier B.V. All rights reserved.

78 FR 10107 - Food and Drug Administration Food Safety Modernization Act: Proposed Rules To Establish Standards...

Science.gov (United States)

2013-02-13

... AGENCY: Food and Drug Administration, HHS. ACTION: Notification of public meeting. SUMMARY: The Food and Drug Administration (FDA) is providing public meeting registration information for two FSMA related... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 16, 106, 110...

75 FR 73107 - Guidance for Industry and Food and Drug Administration Staff; Blood Lancet Labeling; Availability

Science.gov (United States)

2010-11-29

...] Guidance for Industry and Food and Drug Administration Staff; Blood Lancet Labeling; Availability AGENCY... announcing the availability of the guidance entitled ``Guidance for Industry and Food and Drug Administration... single copies of the guidance document entitled ``Guidance for Industry and Food and Drug Administration...

75 FR 36425 - Guidance for Industry and Food and Drug Administration Staff; In Vitro Diagnostic Studies...

Science.gov (United States)

2010-06-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0076] (formerly Docket No. 2007D-0387) Guidance for Industry and Food and Drug Administration Staff; In Vitro Diagnostic Studies--Frequently Asked Questions; Availability AGENCY: Food and Drug Administration, HHS...

75 FR 53971 - Guidance for Industry and Food and Drug Administration Staff; Impact-Resistant Lenses: Questions...

Science.gov (United States)

2010-09-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0367] Guidance for Industry and Food and Drug Administration Staff; Impact-Resistant Lenses: Questions and Answers; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...

76 FR 68767 - Draft Guidance for Industry and Food and Drug Administration Staff; De Novo Classification...

Science.gov (United States)

2011-11-07

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0689] Draft Guidance for Industry and Food and Drug Administration Staff; De Novo Classification Process... for Industry and Food and Drug Administration Staff; De Novo Classification Process (Evaluation of...

77 FR 74195 - Draft Guidance for Industry and Food and Drug Administration Staff; Design Considerations for...

Science.gov (United States)

2012-12-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1161] Draft Guidance for Industry and Food and Drug Administration Staff; Design Considerations for Devices Intended for Home Use; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The...

78 FR 5185 - Guidance for Industry and Food and Drug Administration Staff; Humanitarian Use Device (HUD...

Science.gov (United States)

2013-01-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0847] Guidance for Industry and Food and Drug Administration Staff; Humanitarian Use Device (HUD) Designations... public comment ``Draft Guidance for Industry and Food and Drug Administration Staff on Humanitarian Use...

Estimating preferences for modes of drug administration: The case of US healthcare professionals.

Science.gov (United States)

Tetteh, Ebenezer K; Morris, Steve; Titchener-Hooker, Nigel

2018-01-01

There are hidden drug administration costs that arise from a mismatch between end-user preferences and how manufacturers choose to formulate their drug products for delivery to patients. The corollary of this is: there are "intangible benefits" from considering end-user preferences in manufacturing patient-friendly medicines. It is important then to have some idea of what pharmaceutical manufacturers should consider in making patient-friendly medicines and of the magnitude of the indirect benefits from doing so. This study aimed to evaluate preferences of healthcare professionals in the US for the non-monetary attributes of different modes of drug administration. It uses these preference orderings to compute a monetary valuation of the indirect benefits from making patient-friendly medicines. A survey collected choice preferences of a sample of 210 healthcare professionals in the US for two unlabelled drug options. These drugs were identical except in the levels of attributes of drug administration. Using the choice data collected, statistical models were estimated to compute gross welfare benefits, measured by the expected compensating variation, from making drugs in a more patient-friendly manner. The monetary value of end-user benefits from developing patient-friendly drug delivery systems is: (1) as large as the annual acquisition costs per full treatment episode for some biologic drugs; and (2) likely to fall in the "high end" of the distribution of the direct monetary costs of drug administration. An examination of end-user preferences should help manufacturers make more effective and efficient use of limited resources for innovations in drug delivery system, or manufacturing research in general. Copyright © 2017 Elsevier Inc. All rights reserved.

77 FR 37058 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

Science.gov (United States)

2012-06-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA 2012-D-0304] Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance... Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the...

Adverse Drug Event Monitoring at the Food and Drug Administration: Your Report Can Make a Difference

OpenAIRE

Ahmad, Syed Rizwanuddin

2003-01-01

The Food and Drug Administration (FDA) is responsible not only for approving drugs but also for monitoring their safety after they reach the market. The complete adverse event profile of a drug is not known at the time of approval because of the small sample size, short duration, and limited generalizability of pre-approval clinical trials. This report describes the FDA's postmarketing surveillance system, to which many clinicians submit reports of adverse drug events encountered while treati...

FDA approves efavirenz. Food and Drug Administration.

Science.gov (United States)

Highleyman, L

1998-10-01

The Food and Drug Administration (FDA) approved DuPont Pharma's new non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (Sustiva, DMP-266). Efavirenz has shown promise in trials with over 2000 participants for up to 24 weeks, and early data suggests it may be as effective as protease inhibitors when used in a combination regimen. It is the first anti-HIV drug approved for once-daily dosing. Efavirenz is well tolerated, and the main side effects reported are dizziness, insomnia, abnormal dreams, and skin rash. Efavirenz has been approved for adults and children, but should not be used by pregnant women. Contact information is provided.

Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts.

Science.gov (United States)

Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A

2013-09-01

This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3: 1 morphine : oxycodone oral dose ratio yielded equivalent subjective and physiological effects in nondependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures - that is, a drug versus money and a drug versus drug procedure - were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater than those of high-dose morphine. The study demonstrated that a 3: 1 oral dose ratio of morphine : oxycodone was not equipotent in buprenorphine-dependent individuals. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest.

Enhancing topical analgesic administration: review and prospect for transdermal and transbuccal drug delivery systems.

Science.gov (United States)

Sanz, Roser; Calpena, Ana C; Mallandrich, Mireia; Clares, Beatriz

2015-01-01

Topical administration is an appealing method for drug delivery due to its non-invasiveness, self-controlled application, avoidance of first-pass metabolism in the liver and reduction of systemic side effects compared to other conventional routes such as oral and parenteral. However, topical administration must overcome the permeable barriers that skin and mucosa represent for the drug to achieve its desired therapeutic effect. Penetration of drugs through human skin is mainly impaired by the stratum corneum- the uppermost keratinized skin layer. In contrast, the stratified squamous epithelium (a nonkeratinized tissue) represents the major physical barrier for transbuccal drug administration in humans. Different technologies have been studied to enhance the bioavailability or local effects of drugs administered through skin and buccal mucosa. Those technologies involve the use of physical or chemical enhancers and new dosage forms such as vesicles, cyclodextrins, nanoparticles and other complex systems. Combinations of these technologies may further increase drug delivery in some cases. As analgesia is one of the main therapeutic effects sought through topical administration, this paper focuses on the review of drug delivery systems to improve the topical and transdermal/transbuccal drug delivery of substances with known analgesic action. A discussion of their possibilities and limitations is also included.

Frequency and determinants of drug administration errors in the intensive care unit

NARCIS (Netherlands)

van den Bemt, PMLA; Fijn, R; van der Voort, PHJ; Gossen, AA; Egberts, TCG; Brouwers, JRBJ

Objective., The study aimed to identify both the frequency and the determinants of drug administration errors in the intensive care unit. Design: Administration errors were detected by using the disguised-observation technique (observation of medication administrations by nurses, without revealing

77 FR 5027 - Food and Drug Administration Transparency Initiative: Exploratory Program To Increase Access to...

Science.gov (United States)

2012-02-01

...] Food and Drug Administration Transparency Initiative: Exploratory Program To Increase Access to the... entitled ``Food and Drug Administration Transparency Initiative: Exploratory Program to [[Page 5028

1 Impact of praziquantel mass drug administration campaign on ...

African Journals Online (AJOL)

used to collect information on MDA uptake, knowledge of schistosomiasis, sources .... transmission and in which Praziquantel mass drug administration has been ..... MoHSW (2012) Tanzania Mainland Strategic Master Plan for the Neglected ...

76 FR 55928 - Food and Drug Administration Health Professional Organizations Conference

Science.gov (United States)

2011-09-09

...] Food and Drug Administration Health Professional Organizations Conference AGENCY: Food and Drug... conference for representatives of Health Professional Organizations. Dr. Margaret Hamburg, Commissioner of... person attending, the name of the organization, address, and telephone number. There is no registration...

Pharmaceutical assistance in the enteral administration of drugs: choosing the appropriate pharmaceutical formulation

Directory of Open Access Journals (Sweden)

Gisele de Lima

2009-03-01

Full Text Available Objective: To study solid medications for oral delivery on the formulary of Hospital Israelita Albert Einstein (HIAE, investigating the  possibility of using these drugs through enteral feeding tubes, and recommending appropriate administration. Methods: Study carried out through survey of solid medications for oral delivery included on the formulary of HIAE, literature review, and analysis of medication monographs, manufacturer information and pharmacotechnical data of active ingredients and excipients. It was observed the factors that might hinder or complicate the administration of these drugs though enteral tubes, and was drawn an information chart with recommendations about drug administration in this context. Rresults: The study evaluated 234 medications; and the main problems of administering these drugs through enteral feeding tubes were as follows: changes in drug pharmacokinetics (38; gastrointestinal damage (9; risk of obstruction (40, drug-nutrient interactions (7; biological hazards (5 and no information (33. Cconclusions: Compiling this information helps the healthcare team to choose the appropriate pharmaceutical formulation for medications administered through enteral tubes, and may help identify adverse events related to this technique.

Investigation of the mechanisms of action behind Electromotive Drug Administration (EMDA)

DEFF Research Database (Denmark)

Kos, Bor; Vasquez, Juan Luis; Miklavčič, D

2016-01-01

Objective. Bladder cancer is a cause of considerable morbidity worldwide. Electromotive Drug Administration is a method that combines intravesical chemotherapy with local electric field application. Electroporation has been suggested among other mechanisms as having a possible role in the therapy......, so the goal of the present study was to investigate the electric fields present in the bladder wall during the treatment to determine which mechanisms might be involved. Material and Methods. Electromotive Drug Administration involves applying intravesical mitomycin C with direct current of 20 m...

Patient-Reported Outcomes in Cancer Drug Development and US Regulatory Review: Perspectives From Industry, the Food and Drug Administration, and the Patient.

Science.gov (United States)

Basch, Ethan; Geoghegan, Cindy; Coons, Stephen Joel; Gnanasakthy, Ari; Slagle, Ashley F; Papadopoulos, Elektra J; Kluetz, Paul G

2015-06-01

Data reported directly by patients about how they feel and function are rarely included in oncology drug labeling in the United States, in contrast to Europe and to nononcology labeling in the United States, where this practice is more common. Multiple barriers exist, including challenges unique to oncology trials, and industry's concerns regarding cost, logistical complexities, and the Food and Drug Administration's (FDA's) rigorous application of its 2009 guidance on the use of patient-reported outcome (PRO) measures. A panel consisting of representatives of industry, FDA, the PRO Consortium, clinicians, and patients was assembled at a 2014 workshop cosponsored by FDA to identify practical recommendations for overcoming these barriers. Key recommendations included increasing proactive encouragement by FDA to clinical trial sponsors for including PROs in drug development programs; provision of comprehensive PRO plans by sponsors to FDA early in drug development; promotion of an oncology-specific PRO research agenda; development of an approach to existing ("legacy") PRO measures, when appropriate (focused initially on symptoms and functional status); and increased FDA and industry training in PRO methodology. FDA has begun implementing several of these recommendations.

Assessment of knowledge of pediatric nurses related with drug administration and preparation.

Science.gov (United States)

Bülbül, Ali; Kunt, Ayşe; Selalmaz, Melek; Sözeri, Şehrinaz; Uslu, Sinan; Nuhoğlu, Asiye

2014-12-01

Aim of this study is to determine the levels of knowledge related with drug administration and drug administration errors of nurses who care for pediatric patients. The study data were obtained from the nurses who were working in the departments of pediatrics in two education and research hospitals in the province of İstanbul and who accepted to participate in the study. The questionnaire form of the study was established by the investigators in accordance with the experiences and literature information. A total of 31 questions related with drug preparation, calculation and administration together with the general working properties of the individual were filled out by face to face interview. The data were evaluated using percent and chi-square tests. The study was initiated after ethics committee approval was obtained from Şişli Hamidiye Etfal Education and Research Hospital (365/2013). The study was conducted with 98 nurses who accepted the questionnaire. The education levels of the participants were as follows: undergraduate (48%), high school (32.7%), associate degree (12.2%), master's degree (6.1%) and postgraduate (1%). It was found that 88.8% of the participants worked in a patient-centered fashion and 11.2% worked in a work-centered fashion. The frequency of interruption/distraction during preparation of treatment was found to be 92.9%. It was found that the frequency of checking by two people during preparation or administration of high risk drugs was 64.3% and the conditions under which drugs should be kept were found to known correctly with a rate of 76.5%. It was found that undergraduate healthcare workers were more successful in converting units (p= 0.000). It was found that powder weight of drugs was considered with a rate of 85.7% in calculation. Conclusively, it was found that nurses who worked in pediatric wards did not receive a standard education in terms of drug administration and preparation. It was found that undergraduate nurses were more

77 FR 45357 - Draft Guidance for Industry and Food and Drug Administration Staff; Acceptance and Filing Review...

Science.gov (United States)

2012-07-31

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0524] Draft Guidance for Industry and Food and Drug Administration Staff; Acceptance and Filing Review for Premarket Approval Applications; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice...

77 FR 27461 - Draft Guidance for Industry and Food and Drug Administration Staff; Pediatric Information for X...

Science.gov (United States)

2012-05-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0384] Draft Guidance for Industry and Food and Drug Administration Staff; Pediatric Information for X-Ray Imaging Device Premarket Notifications; Availability AGENCY: Food and Drug Administration, HHS. ACTION...

77 FR 14403 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Science.gov (United States)

2012-03-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0167] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Norovirus Serological Reagents; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice...

Model-based drug administration : current status of target-controlled infusion and closed-loop control

NARCIS (Netherlands)

Kuizenga, Merel H.; Vereecke, Hugo E. M.; Struys, Michel M. R. F.

Purpose of review Drug administration might be optimized by incorporating pharmacokinetic-dynamic (PK/PD) principles and control engineering theories. This review gives an update of the actual status of target-controlled infusion (TCI) and closed-loop computer-controlled drug administration and the

Zohydro approval by food and drug administration: controversial or frightening?

Science.gov (United States)

Manchikanti, Laxmaiah; Atluri, Sairam; Candido, Kenneth D; Boswell, Mark V; Simopoulos, Thomas T; Grider, Jay S; Falco, Frank J E; Hirsch, Joshua A

2014-01-01

The actions and regulations of the Food and Drug Administration (FDA) are crucial to the entire population of the U.S., specifically the public who take a multitude of drugs and providers who prescribe drugs and devices. Further, the FDA is relevant to investors, specifically in regards to biotech and pharmaceutical companies involved in developing new drugs. The FDA has been criticized for a lack of independence on the one hand and excessive regulatory and expanding authority without evidence and consistency of the actions on the other hand. The FDA approved a single-entity, long-acting, hydrocodone product (Zohydro, Zogenix, San Diego, CA) on October 25, 2013, against the recommendation of the FDA's own appointed scientific advisory panel, which voted 11 to 2 against the approval of Zohydro. Subsequent to the approval, multiple consumer safety organizations, health care agencies, addiction treatment providers, professional organizations, and other groups on the frontline of the opioid addiction epidemic have expressed concern. In addition, the US Congress and various state attorneys general raised serious concerns about the approval of Zohydro, which is highly addictive and may enhance the opioid addiction epidemic. Supporters of Zohydro contend that it is necessary and essential to manage chronic pain and improve functional status with no additional risk. Over the past 15 years, prescriptions for opioids have skyrocketed with the United States consuming more than 84% of the global oxycodone and more than 99% of the hydrocodone supply. The sharp increase in opioid prescribing has led to parallel increases in opioid addiction and overdose deaths, surpassing motor vehicle injuries in the U.S. Recent studies assessing the trends of medical use and misuse of opioid analgesics from 2000 to 2011 have concluded that the present trend of the continued increase in the medical use of opioid analgesics appears to contribute to increasing misuse, resulting in multiple health

76 FR 20992 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Science.gov (United States)

2011-04-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0189] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Low Level Laser System for Aesthetic Use; Availability AGENCY: Food and Drug Administration, HHS...

75 FR 68364 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Science.gov (United States)

2010-11-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2008-D-0275] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Full-Field Digital Mammography System; Availability AGENCY: Food and Drug Administration, HHS. [[Page...

76 FR 16425 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Science.gov (United States)

2011-03-23

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0028] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Ovarian Adnexal Mass Assessment Score Test System; Availability AGENCY: Food and Drug Administration, HHS...

76 FR 6622 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Science.gov (United States)

2011-02-07

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0645] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Contact Cooling System for Aesthetic Use; Availability AGENCY: Food and Drug Administration, HHS. ACTION...

76 FR 22906 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Science.gov (United States)

2011-04-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2006-D-0094] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Topical Oxygen Chamber for Extremities; Availability AGENCY: Food and Drug Administration, HHS. ACTION...

78 FR 101 - Guidance for Industry and Food and Drug Administration Staff; Acceptance and Filing Reviews for...

Science.gov (United States)

2013-01-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0524] Guidance for Industry and Food and Drug Administration Staff; Acceptance and Filing Reviews for Premarket Approval Applications; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The...

76 FR 43332 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Science.gov (United States)

2011-07-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0500] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Focused Ultrasound Stimulator System for Aesthetic Use; Availability AGENCY: Food and Drug Administration...

76 FR 51993 - Draft Guidance for Industry and Food and Drug Administration Staff on In Vitro Companion...

Science.gov (United States)

2011-08-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0215] Draft Guidance for Industry and Food and Drug Administration Staff on In Vitro Companion Diagnostic Devices; Extension of Comment Period AGENCY: Food and Drug Administration, HHS. ACTION: Notice; extension...

76 FR 77542 - Draft Guidance for Industry and Food and Drug Administration Staff on Humanitarian Use Device...

Science.gov (United States)

2011-12-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0847] Draft Guidance for Industry and Food and Drug Administration Staff on Humanitarian Use Device Designations; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...

ALTERNATIVE ROUTES OF DRUG ADMINISTRATION: ADVANTAGES AND DISADVANTAGES (SUBJECT REVIEW OF AMERICAN ACADEMY OF PEDIATRICS

Directory of Open Access Journals (Sweden)

article editorial

2006-01-01

Full Text Available During the past 20 years advances in drug formulations and innovative routes of administration have been made. Our understanding of drug transport across tissues has increased. These changes have often resulted in improved patient adherence to the therapeutic regiment and pharmacologic response. The administration of drugs by transdermal or transmucosal routes offers the advantage of being relatively painless. Also, the potential for greater flexibility in a variety of clinical situations exists, often precluding the need to establish intravinus access which is a particular benefit for children. This statement focuses on the advantages and disadvantages of alternative routes of drug administration. Issues of particular importance in the care of pediatric patients especially factors that could lead to drug-relaxed toxicity or adverse responses are emphasized.Key words: drug formulation, pharmacoKINETICS, pharmacodynamics, drug, children.

77 FR 16123 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

Science.gov (United States)

2012-03-19

... Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document... Drug Administration 21 CFR Part 866 Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Nucleic Acid-Based In Vitro Diagnostic Devices for the...

76 FR 29251 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls; Guidance...

Science.gov (United States)

2011-05-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2006-D-0094] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls; Guidance Document... of the guidance entitled ``Guidance for Industry and Food and Drug Administration Staff; Class II...

78 FR 102 - Guidance for Industry and Food and Drug Administration Staff; eCopy Program for Medical Device...

Science.gov (United States)

2013-01-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1056] Guidance for Industry and Food and Drug Administration Staff; eCopy Program for Medical Device Submissions; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...

75 FR 69591 - Medicaid Program; Withdrawal of Determination of Average Manufacturer Price, Multiple Source Drug...

Science.gov (United States)

2010-11-15

..., Multiple Source Drug Definition, and Upper Limits for Multiple Source Drugs AGENCY: Centers for Medicare... withdrawing the definition of ``multiple source drug'' as it was revised in the ``Medicaid Program; Multiple Source Drug Definition'' final rule published in the October 7, 2008 Federal Register. DATES: Effective...

77 FR 14404 - Guidance for the Public, Food and Drug Administration (FDA) Advisory Committee Members, and FDA...

Science.gov (United States)

2012-03-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2002-D-0094; (formerly Docket No. 02D-0049)] Guidance for the Public, Food and Drug Administration (FDA) Advisory... Food and Drug Administration (FDA) is announcing the availability of a guidance for the public, FDA...

77 FR 48159 - Draft Guidance for Industry and Food and Drug Administration Staff; Refuse To Accept Policy for...

Science.gov (United States)

2012-08-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0523] Draft Guidance for Industry and Food and Drug Administration Staff; Refuse To Accept Policy for 510(k)s; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...

Drug distribution in man: a positron emission tomography study after oral administration of the labelled neuroprotective drug vinpocetine

International Nuclear Information System (INIS)

Gulyas, Balazs; Halldin, Christer; Sandell, Johan; Farde, Lars; Sovago, Judit; Cselenyi, Zsolt; Vas, Adam; Kiss, Bela; Karpati, Egon

2002-01-01

Direct information on the distribution of a drug requires measurements in various tissues. Such data have until now been obtained in animals, or have indirectly been calculated from plasma measurements in humans using mathematical models. Here we suggest the use of positron emission tomography (PET) as a method to obtain direct measurements of drug distribution in the human body. The distribution in body and brain of vinpocetine, a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases, was followed after oral administration. Vinpocetine was labelled with carbon-11 and radioactivity was measured by PET in stomach, liver, brain and kidney in six healthy volunteers. The radioactivity in blood and urine as well as the fractions of [ 11 C]vinpocetine and labelled metabolites in plasma were also determined. After oral administration, [ 11 C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the administration of the labelled drug. Brain distribution was heterogeneous, similar to the distribution previously reported after intravenous administration. These findings indicate that vinpocetine, administered orally in humans, readily enters the bloodstream from the stomach and gastrointestinal tract and, consequently, passes the blood-brain barrier and enters the brain. Radioactivity from [ 11 C]vinpocetine was also demonstrated in the kidneys and in urine, indicating that at least a part of the radioactive drug and labelled metabolites is eliminated from the body through the kidneys. This study is the first to demonstrate that PET might be a useful, direct and non-invasive tool to study the distribution and pharmacokinetics of orally

Drug distribution in man: a positron emission tomography study after oral administration of the labelled neuroprotective drug vinpocetine.

Science.gov (United States)

Gulyás, Balázs; Halldin, Christer; Sóvágó, Judit; Sandell, Johan; Cselényi, Zsolt; Vas, Adám; Kiss, Béla; Kárpáti, Egon; Farde, Lars

2002-08-01

Direct information on the distribution of a drug requires measurements in various tissues. Such data have until now been obtained in animals, or have indirectly been calculated from plasma measurements in humans using mathematical models. Here we suggest the use of positron emission tomography (PET) as a method to obtain direct measurements of drug distribution in the human body. The distribution in body and brain of vinpocetine, a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases, was followed after oral administration. Vinpocetine was labelled with carbon-11 and radioactivity was measured by PET in stomach, liver, brain and kidney in six healthy volunteers. The radioactivity in blood and urine as well as the fractions of [(11)C]vinpocetine and labelled metabolites in plasma were also determined. After oral administration, [(11)C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the administration of the labelled drug. Brain distribution was heterogeneous, similar to the distribution previously reported after intravenous administration. These findings indicate that vinpocetine, administered orally in humans, readily enters the bloodstream from the stomach and gastrointestinal tract and, consequently, passes the blood-brain barrier and enters the brain. Radioactivity from [(11)C]vinpocetine was also demonstrated in the kidneys and in urine, indicating that at least a part of the radioactive drug and labelled metabolites is eliminated from the body through the kidneys. This study is the first to demonstrate that PET might be a useful, direct and non-invasive tool to study the distribution and pharmacokinetics of orally

75 FR 21000 - Draft Guidance for the Public, Food and Drug Administration Advisory Committee Members, and Food...

Science.gov (United States)

2010-04-22

...] (formerly Docket No. 02D-0049) Draft Guidance for the Public, Food and Drug Administration Advisory Committee Members, and Food and Drug Administration Staff: Public Availability of Advisory Committee Members... and Drug Administration Amendments Act of 2007, Public Law No. 110-85), and section 701 (21 U.S.C. 371...

75 FR 44267 - Draft Guidance for Industry and Food and Drug Administration Staff; Medical Devices; Neurological...

Science.gov (United States)

2010-07-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0495] Draft Guidance for Industry and Food and Drug Administration Staff; Medical Devices; Neurological and Physical Medicine Device Guidance Document; Reopening of Comment Period AGENCY: Food and Drug...

78 FR 11654 - Draft Guidance for Industry and Food and Drug Administration Staff; Providing Information About...

Science.gov (United States)

2013-02-19

...] Draft Guidance for Industry and Food and Drug Administration Staff; Providing Information About... Guidance for Industry and Food and Drug Administration Staff: Providing Information About Pediatric Uses of...ComplianceRegulatoryInformation/default.htm . To receive ``Draft Guidance for Industry and Food and Drug...

Factors influencing drug uptake during mass drug administration for control of lymphatic filariasis in rural and urban Tanzania

DEFF Research Database (Denmark)

Kisoka, William J.; Simonsen, Paul Erik; Malecela, Mwelecele N.

2014-01-01

BACKGROUND: In most countries of Sub-Saharan Africa, control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole. Treatment coverages are however often suboptimal for programmes to reach the goal of transmission interrupt......BACKGROUND: In most countries of Sub-Saharan Africa, control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole. Treatment coverages are however often suboptimal for programmes to reach the goal of transmission...

The normalized administration of hybrid operating room: its practical application in managing multiple injuries

International Nuclear Information System (INIS)

Li Xue; Zhang Weiguo; Zhang Lianyang; Chen Tingjing; Chen Jinhua

2011-01-01

Objective: Through carrying out the normalized administration of hybrid operating room the application of the operating room is expanded to the performing of multiple injuries, and, in this way, the operative management become standardized and programmed, the cooperation and efficiency of hybrid operations for multiple injuries are improved and the surgeries can be ensured. Methods: According to the characteristics of hybrid interventional operation for multiple injuries, the basic construction of the hybrid operating room improved, the hybrid operation team was organized, and the administrative system as well as the working program were established. The green channel for rescuing patients with multiple injuries was set up. The cooperative behavior during interventional treatment for multiple injuries was specified. Results: The coordination and working efficiency of physicians, nurses, technicians and anesthetists were well improved. The qualified rate of lamina flow administration reached 100%. The success rate of the rescue of multiple injuries was increased. Conclusion: As one-stop complex interventional operation for multiple injuries is a new technique, there is no integrated administration system. Therefore, the establishment of standardized management of one-stop complex interventional operation is of great significance in guiding clinical practice. (authors)

76 FR 61103 - Draft Guidance for Industry and Food and Drug Administration Staff; De Novo Classification...

Science.gov (United States)

2011-10-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0689] Draft Guidance for Industry and Food and Drug Administration Staff; De Novo Classification Process... appropriate, and other forms of information technology. Draft Guidance for Industry and Food and Drug...

A Multiple Indicators Multiple Causes (MIMIC) model of internal barriers to drug treatment in China.

Science.gov (United States)

Qi, Chang; Kelly, Brian C; Liao, Yanhui; He, Haoyu; Luo, Tao; Deng, Huiqiong; Liu, Tieqiao; Hao, Wei; Wang, Jichuan

2015-03-01

Although evidence exists for distinct barriers to drug abuse treatment (BDATs), investigations of their inter-relationships and the effect of individual characteristics on the barrier factors have been sparse, especially in China. A Multiple Indicators Multiple Causes (MIMIC) model is applied for this target. A sample of 262 drug users were recruited from three drug rehabilitation centers in Hunan Province, China. We applied a MIMIC approach to investigate the effect of gender, age, marital status, education, primary substance use, duration of primary drug use, and drug treatment experience on the internal barrier factors: absence of problem (AP), negative social support (NSS), fear of treatment (FT), and privacy concerns (PC). Drug users of various characteristics were found to report different internal barrier factors. Younger participants were more likely to report NSS (-0.19, p=0.038) and PC (-0.31, p<0.001). Compared to other drug users, ice users were more likely to report AP (0.44, p<0.001) and NSS (0.25, p=0.010). Drug treatment experiences related to AP (0.20, p=0.012). In addition, differential item functioning (DIF) occurred in three items when participant from groups with different duration of drug use, ice use, or marital status. Individual characteristics had significant effects on internal barriers to drug treatment. On this basis, BDAT perceived by different individuals could be assessed before tactics were utilized to successfully remove perceived barriers to drug treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Having multiple sexual partners among Iranian Injection Drug Users

Directory of Open Access Journals (Sweden)

Shervin eAssari

2014-10-01

Full Text Available Background: Transmission of HIV from intra-venous drug users (IDUs to the community occurs predominantly through high-risk sexual behaviors. Limited information exists regarding the high-risk sexual behaviors of IDUs in Iran. Aim. The aim of this study was to determine the prevalence and factors associated with having multiple sexual partners among Iranian IDUs. Methods. This is a national survey on drug-dependent adults. Participants were sampled from medical centers, prisons, and streets of capitals of 29 provinces in Iran, between May 2007 and February 2008. We analyzed data of 1,416 current IDUs. Socio-demographics and drug use characteristics were entered into a binary logistic regression model to determine predictors of having multiple sexual partners. Results. Having multiple sexual partners in the past or at the time of survey was reported by 56.4% of Iranian IDUs. Multivariate analysis showed that the likelihood of having multiple sexual partners in IDUs decreased by being married (odds ratio [OR], 0.38; P < .001 and increased by female gender (OR, 13.44; P = .02, having illegal income (OR, 1.72; P = .003, higher monthly family income (OR, 1.01; P = .003, pleasure, curiosity, and recreation as cause of first drug use (OR, 1.37; P = .04, ruins as usual place for injection (OR, 1.89; P = .001, and history of syringe sharing (OR, 1.50; P = .02. Conclusions. Having multiple sexual partners was reported by majority of Iranian IDUs, and this was linked to socio-demographics, initiation data, and other risk behaviors. This information should be considered in prevention efforts to reduce sexual transmission of HIV infection in Iran.

75 FR 31450 - Memorandum of Understanding by and Between the United States Food and Drug Administration and the...

Science.gov (United States)

2010-06-03

... Administration and the International Anesthesia Research Society for the Safety of Key Inhaled and Intravenous Drugs in Pediatrics Public-Private Partnership AGENCY: Food and Drug Administration, HHS. ACTION: Notice... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0004...

28 CFR 16.98 - Exemption of the Drug Enforcement Administration (DEA)-limited access.

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2010-07-01

... Administration (DEA)-limited access. 16.98 Section 16.98 Judicial Administration DEPARTMENT OF JUSTICE PRODUCTION... Exemption of the Drug Enforcement Administration (DEA)—limited access. (a) The following systems of records.../Diversion Analysis and Detection System (ARCOS/DADS) (Justice/DEA-003) (2) Controlled Substances Act...

77 FR 70166 - Provisions of the Food and Drug Administration Safety and Innovation Act Related to Medical Gases...

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2012-11-23

...; Establishment of a Public Docket AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is establishing a public docket for information pertaining to FDA's... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1090...

77 FR 63837 - Draft Guidance for Industry and Food and Drug Administration Staff; eCopy Program for Medical...

Science.gov (United States)

2012-10-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1056] Draft Guidance for Industry and Food and Drug Administration Staff; eCopy Program for Medical Device Submissions; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...

Drug distribution in man: a positron emission tomography study after oral administration of the labelled neuroprotective drug vinpocetine

Energy Technology Data Exchange (ETDEWEB)

Gulyas, Balazs [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 171 76 Stockholm (Sweden); Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm (Sweden); Halldin, Christer; Sandell, Johan; Farde, Lars [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 171 76 Stockholm (Sweden); Sovago, Judit; Cselenyi, Zsolt [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 171 76 Stockholm (Sweden); Department of Neurology, Faculty of Medicine, University of Debrecen, Debrecen (Hungary); Vas, Adam; Kiss, Bela; Karpati, Egon [Chemical Works of Gedeon Richter Ltd., Budapest (Hungary)

2002-08-01

Direct information on the distribution of a drug requires measurements in various tissues. Such data have until now been obtained in animals, or have indirectly been calculated from plasma measurements in humans using mathematical models. Here we suggest the use of positron emission tomography (PET) as a method to obtain direct measurements of drug distribution in the human body. The distribution in body and brain of vinpocetine, a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases, was followed after oral administration. Vinpocetine was labelled with carbon-11 and radioactivity was measured by PET in stomach, liver, brain and kidney in six healthy volunteers. The radioactivity in blood and urine as well as the fractions of [{sup 11}C]vinpocetine and labelled metabolites in plasma were also determined. After oral administration, [{sup 11}C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the administration of the labelled drug. Brain distribution was heterogeneous, similar to the distribution previously reported after intravenous administration. These findings indicate that vinpocetine, administered orally in humans, readily enters the bloodstream from the stomach and gastrointestinal tract and, consequently, passes the blood-brain barrier and enters the brain. Radioactivity from [{sup 11}C]vinpocetine was also demonstrated in the kidneys and in urine, indicating that at least a part of the radioactive drug and labelled metabolites is eliminated from the body through the kidneys. This study is the first to demonstrate that PET might be a useful, direct and non-invasive tool to study the distribution and

Multimodal system designed to reduce errors in recording and administration of drugs in anaesthesia: prospective randomised clinical evaluation.

Science.gov (United States)

Merry, Alan F; Webster, Craig S; Hannam, Jacqueline; Mitchell, Simon J; Henderson, Robert; Reid, Papaarangi; Edwards, Kylie-Ellen; Jardim, Anisoara; Pak, Nick; Cooper, Jeremy; Hopley, Lara; Frampton, Chris; Short, Timothy G

2011-09-22

To clinically evaluate a new patented multimodal system (SAFERSleep) designed to reduce errors in the recording and administration of drugs in anaesthesia. Prospective randomised open label clinical trial. Five designated operating theatres in a major tertiary referral hospital. Eighty nine consenting anaesthetists managing 1075 cases in which there were 10,764 drug administrations. Use of the new system (which includes customised drug trays and purpose designed drug trolley drawers to promote a well organised anaesthetic workspace and aseptic technique; pre-filled syringes for commonly used anaesthetic drugs; large legible colour coded drug labels; a barcode reader linked to a computer, speakers, and touch screen to provide automatic auditory and visual verification of selected drugs immediately before each administration; automatic compilation of an anaesthetic record; an on-screen and audible warning if an antibiotic has not been administered within 15 minutes of the start of anaesthesia; and certain procedural rules-notably, scanning the label before each drug administration) versus conventional practice in drug administration with a manually compiled anaesthetic record. Primary: composite of errors in the recording and administration of intravenous drugs detected by direct observation and by detailed reconciliation of the contents of used drug vials against recorded administrations; and lapses in responding to an intermittent visual stimulus (vigilance latency task). Secondary: outcomes in patients; analyses of anaesthetists' tasks and assessments of workload; evaluation of the legibility of anaesthetic records; evaluation of compliance with the procedural rules of the new system; and questionnaire based ratings of the respective systems by participants. The overall mean rate of drug errors per 100 administrations was 9.1 (95% confidence interval 6.9 to 11.4) with the new system (one in 11 administrations) and 11.6 (9.3 to 13.9) with conventional methods (one

Radiopharmaceutical regulation and Food and Drug Administration policy.

Science.gov (United States)

Rotman, M; Laven, D; Levine, G

1996-04-01

The regulatory policy of the Food and Drug Administration (FDA) on radiopharmaceuticals flows from a rigid, traditional, drug-like interpretation of the FDC Act on the licensing of radiopharmaceuticals. This contributes to significant delays in the drug-approval process for radiopharmaceuticals, which are very costly to the nuclear medicine community and the American public. It seems that radiopharmaceuticals would be better characterized as molecular devices. Good generic rule-making principles include: use of a risk/benefit/cost analysis; intent based on sound science; performance standards prepared by outside experts; a definite need shown by the regulatory agency; to live with the consequences of any erroneous cost estimates; and design individual credential requirements so that additional training results in enhanced professional responsibility. When these common elements are applied to current FDA policy, it seems that the agency is out of sync with the stated goals for revitalizing federal regulatory policies as deemed necessary by the Clinton administration. Recent FDA rulings on positron-emission tomography, Patient Package inserts, and on medical device service accentuate the degree of such asynchronization. Radiopharmaceutical review and licensing flexibility could be dramatically improved by excluding radiopharmaceuticals from the drug category and reviewing them as separate entities. This new category would take into account their excellent record of safety and their lack of pharmacological action. Additionally, their evaluation of efficacy should be based on their ability to provide useful scintiphotos, data, or responses of the physiological system it portends to image, quantitate, or describe. To accomplish the goal of transforming the FDA's rigid, prescriptive policy into a streamlined flexible performance-based policy, the Council on Radionuclides and Radiopharmaceuticals proposal has been presented. In addition, it is suggested that the United

76 FR 43690 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Science.gov (United States)

2011-07-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0149] (Formerly 2007D-0309) Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Electrocardiograph Electrodes; Availability AGENCY: Food and Drug...

78 FR 36711 - Food and Drug Administration Safety and Innovation Act Title VII-Drug Supply Chain; Standards for...

Science.gov (United States)

2013-06-19

... inspections, and drive safety and quality throughout the supply chain. Implementation of these authorities... authorities granted to FDA under Title VII and their importance in ensuring drug safety, effectiveness, and.... FDA-2013-N-0683, FDA-2013-N-0684, and FDA-2013-N-0685] Food and Drug Administration Safety and...

Evaluating the administration costs of biologic drugs: development of a cost algorithm.

Science.gov (United States)

Tetteh, Ebenezer K; Morris, Stephen

2014-12-01

Biologic drugs, as with all other medical technologies, are subject to a number of regulatory, marketing, reimbursement (financing) and other demand-restricting hurdles applied by healthcare payers. One example is the routine use of cost-effectiveness analyses or health technology assessments to determine which medical technologies offer value-for-money. The manner in which these assessments are conducted suggests that, holding all else equal, the economic value of biologic drugs may be determined by how much is spent on administering these drugs or trade-offs between drug acquisition and administration costs. Yet, on the supply-side, it seems very little attention is given to how manufacturing and formulation choices affect healthcare delivery costs. This paper evaluates variations in the administration costs of biologic drugs, taking care to ensure consistent inclusion of all relevant cost resources. From this, it develops a regression-based algorithm with which manufacturers could possibly predict, during process development, how their manufacturing and formulation choices may impact on the healthcare delivery costs of their products.

Multiple sclerosis in Germany: data analysis of administrative prevalence and healthcare delivery in the statutory health system.

Science.gov (United States)

Höer, Ariane; Schiffhorst, Guido; Zimmermann, Anne; Fischaleck, Johann; Gehrmann, Luise; Ahrens, Henrik; Carl, Gunther; Sigel, Karl-Otto; Osowski, Ulrike; Klein, Maria; Bleß, Hans-Holger

2014-09-10

Healthcare-utilization data for multiple sclerosis (MS) are scarce in Germany. The Purpose of the study was to analyse administrative prevalence of MS, medication use and type of specialists involved in MS treatment in the outpatient setting in Bavaria. Pseudonymized claims data from Bavarian Statutory Health Insurance (SHI)-accredited physicians were used. Administrative prevalence of MS was defined as having ≥1 MS diagnosis (International Classification of Diseases, 10th edition, code G35) documented by a neurologist or psychiatrist, or ≥1 prescription for disease-modifying drugs (DMDs)). The administrative prevalence calculated for Bavaria was projected to Germany. DMD prescription and involvement of different specialities in health care service for MS patients was analysed. Administrative prevalence of MS in Bavaria increased from 0.123% to 0.175% of insured persons between 2005 and 2009; when projected, this yielded ~102,000-143,000 patients with MS in the German population. The percentage of patients receiving ≥1 DMD prescription increased from 45.5% to 50.5%. Patients with MS were mainly treated by neurologists in the ambulatory care setting. These results provide important information on the administrative prevalence of MS in Bavaria and on healthcare provision for patients, which is relevant for resource planning in the healthcare sector.

Methodological Study to Develop Standard Operational Protocol on Oral Drug Administration for Children.

Science.gov (United States)

Bijarania, Sunil Kumar; Saini, Sushma Kumari; Verma, Sanjay; Kaur, Sukhwinder

2017-05-01

To develop standard operational protocol (SOP) on oral drug administration and checklist to assess the implementation of the developed SOP. In this prospective methodological study, SOPs were developed in five phases. In the first phase, the preliminary draft of SOPs and checklists were prepared based on literature review, assessment of current practices and focus group discussion (FGD) with bedside working nurses. In the second phase, content validity was checked with the help of Delphi technique (12 experts). Total four drafts were prepared in stages and necessary modifications were made as per suggestions after each Delphi round. Fourth Delphi round was performed after conducting a pilot study. In the fourth phase, all bedside nurses were trained as per SOPs and asked to practice accordingly and observation of thirty oral drug administrations in children was done to check reliability of checklists for implementation of SOPs. In Phase-V, 7 FGDs were conducted with bedside nurses to assess the effectiveness of SOPs. The Content Validity Index (CVI) of SOP and checklists was 99.77%. Overall standardized Cronbach's alpha was calculated as 0.94. All the nurses felt that the SOP is useful. Valid and feasible SOP for drug administration to children through oral route along with valid and reliable checklist were developed. It is recommended to use this document for drug administration to children.

76 FR 81511 - Draft Guidance for Industry and Food and Drug Administration Staff; Center for Devices and...

Science.gov (United States)

2011-12-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0893] Draft Guidance for Industry and Food and Drug Administration Staff; Center for Devices and Radiological... appropriate, and other forms of information technology. Draft Guidance for Industry and Food and Drug...

75 FR 69089 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Science.gov (United States)

2010-11-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0514] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document... Administration (FDA) is announcing the availability of the guidance entitled ``Class II Special Controls Guidance...

Drug overprescription in nursing homes: an empirical evaluation of administrative data.

Science.gov (United States)

Stroka, Magdalena A

2016-04-01

A widely discussed shortcoming of long-term care in nursing homes for the elderly is the inappropriate or suboptimal drug utilization, particularly of psychotropic drugs. Using administrative data from the largest sickness fund in Germany, this study was designed to estimate the effect of institutionalization on the drug intake of the frail elderly. Difference-in-differences propensity score matching techniques were used to compare drug prescriptions for the frail elderly who entered a nursing home with those who remained in the outpatient care system; findings suggest that nursing home residents receive more doses of antipsychotics, antidepressants, and analgesics. The potential overprescription correlates with estimated drug costs of about €87 million per year.

78 FR 100 - Guidance for Industry and Food and Drug Administration Staff; Refuse To Accept Policy for 510(k)s...

Science.gov (United States)

2013-01-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0523] Guidance for Industry and Food and Drug Administration Staff; Refuse To Accept Policy for 510(k)s; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...

76 FR 12742 - Guidance for Industry and Food and Drug Administration Staff; Clinical Investigations of Devices...

Science.gov (United States)

2011-03-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2008-D-0457] Guidance for Industry and Food and Drug Administration Staff; Clinical Investigations of Devices Indicated... other electrical continence devices; protective garment for incontinence; surgical mesh; electrosurgical...

Enhancing food safety: the role of the Food and Drug Administration

National Research Council Canada - National Science Library

Wallace, Robert B; Oria, Maria

2010-01-01

.... Food and Drug Administration's abilities to discover potential threats to food safety and prevent outbreaks of foodborne illness are hampered by impediments to efficient use of its limited resources...

Drug Enforcement Administration.

Science.gov (United States)

Department of Justice, Washington, DC.

This fact sheet contains information relating to drug abuse and abusers; drug traffic legislation; law enforcement; and descriptions of commonly used narcotics, stimulants, depressants, and hallucinogens. Also included is a short but explicit listing of audiovisual aids, an annotated bibliography, and drug identification pictures. The booklet…

Errors in preparation and administration of parenteral drugs in neonatology: evaluation and corrective actions.

Science.gov (United States)

Hasni, Nesrine; Ben Hamida, Emira; Ben Jeddou, Khouloud; Ben Hamida, Sarra; Ayadi, Imene; Ouahchi, Zeineb; Marrakchi, Zahra

2016-12-01

The medication iatrogenic risk is quite unevaluated in neonatology Objective: Assessment of errors that occurred during the preparation and administration of injectable medicines in a neonatal unit in order to implement corrective actions to reduce the occurrence of these errors. A prospective, observational study was performed in a neonatal unit over a period of one month. The practice of preparing and administering injectable medications were identified through a standardized data collection form. These practices were compared with summaries of the characteristics of each product (RCP) and the bibliography. One hundred preparations were observed of 13 different drugs. 85 errors during preparations and administration steps were detected. These errors were divided into preparation errors in 59% of cases such as changing the dilution protocol (32%), the use of bad solvent (11%) and administration errors in 41% of cases as errors timing of administration (18%) or omission of administration (9%). This study showed a high rate of errors during stages of preparation and administration of injectable drugs. In order to optimize the care of newborns and reduce the risk of medication errors, corrective actions have been implemented through the establishment of a quality assurance system which consisted of the development of injectable drugs preparation procedures, the introduction of a labeling system and staff training.

Development of an opioid self-administration assay to study drug seeking in zebrafish.

Science.gov (United States)

Bossé, Gabriel D; Peterson, Randall T

2017-09-29

The zebrafish (Danio rerio) has become an excellent tool to study mental health disorders, due to its physiological and genetic similarity to humans, ease of genetic manipulation, and feasibility of small molecule screening. Zebrafish have been shown to exhibit characteristics of addiction to drugs of abuse in non-contingent assays, including conditioned place preference, but contingent assays have been limited to a single assay for alcohol consumption. Using inexpensive electronic, mechanical, and optical components, we developed an automated opioid self-administration assay for zebrafish, enabling us to measure drug seeking and gain insight into the underlying biological pathways. Zebrafish trained in the assay for five days exhibited robust self-administration, which was dependent on the function of the μ-opioid receptor. In addition, a progressive ratio protocol was used to test conditioned animals for motivation. Furthermore, conditioned fish continued to seek the drug despite an adverse consequence and showed signs of stress and anxiety upon withdrawal of the drug. Finally, we validated our assay by confirming that self-administration in zebrafish is dependent on several of the same molecular pathways as in other animal models. Given the ease and throughput of this assay, it will enable identification of important biological pathways regulating drug seeking and could lead to the development of new therapeutic molecules to treat addiction. Copyright © 2017 Elsevier B.V. All rights reserved.

75 FR 57963 - Draft Guidance for Industry and Food and Drug Administration Staff; Establishing the Performance...

Science.gov (United States)

2010-09-23

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0459] Draft Guidance for Industry and Food and Drug Administration Staff; Establishing the Performance Characteristics of In Vitro Diagnostic Devices for the Detection of Helicobacter pylori; Availability AGENCY: Food...

40 CFR 23.10 - Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Timing of Administrator's action under the Federal Food, Drug, and Cosmetic Act. 23.10 Section 23.10 Protection of Environment ENVIRONMENTAL... action under the Federal Food, Drug, and Cosmetic Act. Unless the Administrator otherwise explicitly...

77 FR 23485 - Food and Drug Administration Patient Network Annual Meeting; Input Into Food and Drug...

Science.gov (United States)

2012-04-19

...: Notice. The Food and Drug Administration (FDA) is announcing a meeting for patients, caregivers..., caregivers, independent patient advocates, and patient advocate groups that seek to: Educate and inform... of patients? (2) What methodological and practical issues should FDA consider as it develops its...

Combined Transcriptomics and Metabolomics in a Rhesus Macaque Drug Administration Study

Directory of Open Access Journals (Sweden)

Kevin J. Lee

2014-10-01

Full Text Available We describe a multi-omic approach to understanding the effects that the anti-malarial drug pyrimethamine has on immune physiology in rhesus macaques (Macaca mulatta. Whole blood and bone marrow RNA-Seq and plasma metabolome profiles (each with over 15,000 features have been generated for five naïve individuals at up to seven time-points before, during and after three rounds of drug administration. Linear modelling and Bayesian network analyses are both considered, alongside investigations of the impact of statistical modeling strategies on biological inference. Individual macaques were found to be a major source of variance for both omic data types, and factoring individuals into subsequent modelling increases power to detect temporal effects. A major component of the whole blood transcriptome follows the bone marrow with a time-delay, while other components of variation are unique to each compartment. We demonstrate that pyrimethamine administration does impact both compartments throughout the experiment, but very limited perturbation of transcript or metabolite abundance following each round of drug exposure is observed. New insights into the mode of action of the drug are presented in the context of pyrimethamine’s predicted effect on suppression of cell division and metabolism in the immune system.

75 FR 32952 - Draft Guidance for Industry and Food and Drug Administration Staff; “‘Harmful and Potentially...

Science.gov (United States)

2010-06-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0281] Draft Guidance for Industry and Food and Drug Administration Staff; ```Harmful and Potentially Harmful... Food, Drug, and Cosmetic Act.'' This draft guidance provides written guidance to industry and FDA staff...

Preventing errors in administration of parenteral drugs: the results of a four-year national patient safety program.

NARCIS (Netherlands)

Blok, C. de; Schilp, J.; Wagner, C.

2013-01-01

Objectives: To evaluate the implementation of a four-year national patient safety program concerning the parenteral drug administration process in the Netherlands. Methods: Structuring the preparation and administration process of parenteral drugs reduces the number of medication errors. A

75 FR 22601 - Draft Guidance for Industry and Food and Drug Administration Staff; User Fees for 513(g...

Science.gov (United States)

2010-04-29

...] Draft Guidance for Industry and Food and Drug Administration Staff; User Fees for 513(g); Requests for... the Internet. To receive ``Draft Guidance for Industry and Food and Drug Administration Staff; User... and Industry Procedures for Section 513(g) Requests for Information under the Federal Food, Drug, and...

A novel method to calculate the extent and amount of drug transported into CSF after intranasal administration.

Science.gov (United States)

Shi, Zhenqi; Zhang, Qizhi; Jiang, Xinguo

2005-01-31

The aim of this paper is to establish a novel method to calculate the extent and amount of drug transported to brain after administration. The cerebrospinal fluid (CSF) was chosen as the target region. The intranasal administration of meptazinol hydrochloride (MEP) was chosen as the model administration and intravenous administration was selected as reference. According to formula transform, the extent was measured by the equation of X(A)CSF, infinity/X0 = Cl(CSF) AUC(0-->infinity)CSF/X0 and the drug amount was calculated by multiplying the dose with the extent. The drug clearance in CSF (Cl(CSF)) was calculated by a method, in which a certain volume of MEP solution was injected directly into rat cistern magna and then clearance was assessed as the reciprocal of the zeroth moment of a CSF level-time curve normalized for dose. In order to testify the accurateness of the method, 14C-sucrose was chosen as reference because of its impermeable characteristic across blood-brain barrier (BBB). It was found out that the MEP concentrations in plasma and CSF after intranasal administration did not show significant difference with those after intravenous administration. However, the extent and amount of MEP transported to CSF was significantly lower compared with those to plasma after these two administrations. In conclusion, the method can be applied to measure the extent and amount of drug transported to CSF, which would be useful to evaluate brain-targeting drug delivery.

Sex differences in the self-administration of cannabinoids and other drugs of abuse.

Science.gov (United States)

Fattore, Liana; Fadda, Paola; Fratta, Walter

2009-12-01

Many studies have provided evidence for important sex-dependent differences in the origins, outcomes and treatment of drug abuse and dependence. Preclinical studies typically have employed animal models of addiction, such as oral or intravenous self-administration, to untangle the environmental, neurobiological and genetic factors that contribute to the shift from occasional, recreational use to compulsive, uncontrolled intake of drugs. Craving and relapse of drug seeking in abstinent individuals have also been found to differ between men and women. Identification of the neurobiological basis of craving and drug dependence continues to pose a challenge to addiction research. Significant sex differences are emerging in substance-abuse-related behavior, which has increased the demand for research on how drug consumption may have different causes, progression and consequences in men and women. In keeping with epidemiological data in humans, differences between the two sexes in drug seeking and intake have been well-documented in animal studies, with most recent findings related to abuse of cannabinoids. Clinical and preclinical findings indicate that sex and gonadal hormones may account for individual differences in susceptibility to the reinforcing effects of addictive substances, and that differences in vulnerability to drug abuse may be mediated by the same biological mechanisms. This review focuses on the differences between males and females in relation to drug self-administration and how such behavior may be affected by hormonal status.

U.S. Food and Drug Administration drug approval: slow advances in obstetric care in the United States.

Science.gov (United States)

Wing, Deborah A; Powers, Barbara; Hickok, Durlin

2010-04-01

The process for drug approval in the United States is complex and time-consuming. There are comparatively few drugs with U.S. Food and Drug Administration (FDA)-approved indications for obstetric use in this country at this time; however, several are under development. We review the process for drug approval and recount the approval histories of obstetric drugs reviewed in the recent past. We also outline the current status of two progestational agents that are under development. For a variety of reasons, including a small market compared with others such as cardiology or oncology, and the potential of being drawn into medical-legal litigation, sponsors are disinclined to pursue drug development for obstetric purposes in this country. We compare the procedures for review and approval of drugs in the United States with those in Europe, and note that recent changes within the FDA may result in not only more drugs being approved but also changes in labeling of already approved drugs. Special programs to facilitate drug development and reforms to modernize the process and improve safety are discussed. These may result in changes in labeling of already approved drugs. Obstacles such as funding and liability are also discussed.

Food and Drug Administration Evaluation and Cigarette Smoking Risk Perceptions

Science.gov (United States)

Kaufman, Annette R.; Waters, Erika A.; Parascandola, Mark; Augustson, Erik M.; Bansal-Travers, Maansi; Hyland, Andrew; Cummings, K. Michael

2011-01-01

Objectives: To examine the relationship between a belief about Food and Drug Administration (FDA) safety evaluation of cigarettes and smoking risk perceptions. Methods: A nationally representative, random-digit-dialed telephone survey of 1046 adult current cigarette smokers. Results: Smokers reporting that the FDA does not evaluate cigarettes for…

Administración de medicamentos por vía oral: Interacciones medicamento - alimento Oral drug administration: drug-food interactions

Directory of Open Access Journals (Sweden)

Nélida Barrueco

2008-03-01

Full Text Available Introducción: la vía oral de administración de medicamentos es la vía más cómoda, segura y económica. Sin embargo, pueden existir interacciones con otros fármacos o con alimentos que alteren la eficacia y seguridad de los mismos. Objetivo: desarrollar un programa de información dirigido a enfermeros y enfermeras sobre la administración de medicamentos por vía oral. Método: se seleccionan los medicamentos más utilizados en el área de cardiología pediátrica, revisándose para cada principio activo la administración en relación con alimentos o productos medicinales y otros aspectos relacionados con la administración por vía oral. Resultados: se elabora una tabla informativa sobre un total de 28 principios activos. Discusión: Los farmacéuticos de hospital se han integrado recientemente en los equipos multidisciplinares y desde esta posición tienen la oportunidad de desarrollar diferentes programas de atención farmacéutica, educación sanitaria e información encaminadas a prevenir problemas relacionados con los medicamentos, aumentar su uso seguro y disminuir los riesgos asociados a cualquier tratamiento farmacológico. Las prescripciones médicas generalmente no indican el horario y la forma de administración de los medicamentos, dejando a enfermeros y enfermeras la responsabilidad de su organización. Por esto deben estar informados de cómo y cuándo se deben administrar los medicamentos, lo que permite garantizar su uso seguro y disminuir los riesgos asociados al tratamiento.Background: The easiest, safest and cheapest way to administrate drugs is by mouth (PO. Nevertheless, there may be interactions, either with other drugs or with food, which can modify efficacy and security of the drug itself. Objective: the development of a nursing information program about the administration of drugs PO. Method: we selected the most used drugs corresponding to the pediatric cardiology area, looking for the best administration

The cost of multiple sclerosis drugs in the US and the pharmaceutical industry

Science.gov (United States)

Bourdette, Dennis N.; Ahmed, Sharia M.; Whitham, Ruth H.

2015-01-01

Objective: To examine the pricing trajectories in the United States of disease-modifying therapies (DMT) for multiple sclerosis (MS) over the last 20 years and assess the influences on rising prices. Methods: We estimated the trend in annual drug costs for 9 DMTs using published drug pricing data from 1993 to 2013. We compared changes in DMT costs to general and prescription drug inflation during the same period. We also compared the cost trajectories for first-generation MS DMTs interferon (IFN)–β-1b, IFN-β-1a IM, and glatiramer acetate with contemporaneously approved biologic tumor necrosis factor (TNF) inhibitors. Results: First-generation DMTs, originally costing $8,000 to $11,000, now cost about $60,000 per year. Costs for these agents have increased annually at rates 5 to 7 times higher than prescription drug inflation. Newer DMTs commonly entered the market with a cost 25%–60% higher than existing DMTs. Significant increases in the cost trajectory of the first-generation DMTs occurred following the Food and Drug Administration approvals of IFN-β-1a SC (2002) and natalizumab (reintroduced 2006) and remained high following introduction of fingolimod (2010). Similar changes did not occur with TNF inhibitor biologics during these time intervals. DMT costs in the United States currently are 2 to 3 times higher than in other comparable countries. Conclusions: MS DMT costs have accelerated at rates well beyond inflation and substantially above rates observed for drugs in a similar biologic class. There is an urgent need for clinicians, payers, and manufacturers in the United States to confront the soaring costs of DMTs. PMID:25911108

Prescription Drug Promotion from 2001-2014: Data from the U.S. Food and Drug Administration.

Directory of Open Access Journals (Sweden)

Helen W Sullivan

Full Text Available The volume of prescription drug promotion over time is often measured by assessing changes in ad spending. However, this method obscures the fact that some types of advertising are more expensive than others. Another way to measure the changes in prescription drug promotion over time is to assess the number of promotional pieces submitted to the U.S. Food and Drug Administration (FDA. Form FDA 2253 collects information such as the date submitted and the type of material submitted. We analyzed data from Forms FDA 2253 received from 2001-2014. We examined the frequency of submissions by audience (consumer and healthcare professional and type of promotional material. There was a noted increase in prescription drug promotion submissions across all media in the early 2000s. Although non-Internet promotion submissions have since plateaued, Internet promotion continued to increase. These results can help public health advocates and regulators focus attention and resources.

Programmable release of multiple protein drugs from aptamer-functionalized hydrogels via nucleic acid hybridization.

Science.gov (United States)

Battig, Mark R; Soontornworajit, Boonchoy; Wang, Yong

2012-08-01

Polymeric delivery systems have been extensively studied to achieve localized and controlled release of protein drugs. However, it is still challenging to control the release of multiple protein drugs in distinct stages according to the progress of disease or treatment. This study successfully demonstrates that multiple protein drugs can be released from aptamer-functionalized hydrogels with adjustable release rates at predetermined time points using complementary sequences (CSs) as biomolecular triggers. Because both aptamer-protein interactions and aptamer-CS hybridization are sequence-specific, aptamer-functionalized hydrogels constitute a promising polymeric delivery system for the programmable release of multiple protein drugs to treat complex human diseases.

78 FR 9701 - Draft Joint Food and Drug Administration/Health Canada Quantitative Assessment of the Risk of...

Science.gov (United States)

2013-02-11

... on the sources of L. monocytogenes contamination, the effects of individual manufacturing and/or... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1182] Draft Joint Food and Drug Administration/Health Canada Quantitative Assessment of the Risk of...

76 FR 48870 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Science.gov (United States)

2011-08-09

... selection inclusion and exclusion criteria section. The revisions define and differentiate the required... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0428] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document...

75 FR 59726 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

Science.gov (United States)

2010-09-28

... method comparison section and the sample selection inclusion and exclusion criteria section. The... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0428] Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

The impact of a multiple intelligences teaching approach drug education programme on drug refusal skills of Nigerian pupils.

Science.gov (United States)

Nwagu, Evelyn N; Ezedum, Chuks E; Nwagu, Eric K N

2015-09-01

The rising incidence of drug abuse among youths in Nigeria is a source of concern for health educators. This study was carried out on primary six pupils to determine the effect of a Multiple Intelligences Teaching Approach Drug Education Programme (MITA-DEP) on pupils' acquisition of drug refusal skills. A programme of drug education based on the Multiple Intelligences Teaching Approach (MITA) was developed. An experimental group was taught using this programme while a control group was taught using the same programme but developed based on the Traditional Teaching Approach. Pupils taught with the MITA acquired more drug refusal skills than those taught with the Traditional Teaching Approach. Urban pupils taught with the MITA acquired more skills than rural pupils. There was no statistically significant difference in the mean refusal skills of male and female pupils taught with the MITA. © The Author(s) 2014.

21 CFR 888.3030 - Single/multiple component metallic bone fixation appliances and accessories.

Science.gov (United States)

2010-04-01

... appliances and accessories. 888.3030 Section 888.3030 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT....3030 Single/multiple component metallic bone fixation appliances and accessories. (a) Identification. Single/multiple component metallic bone fixation appliances and accessories are devices intended to be...

76 FR 78931 - Food and Drug Administration Rare Disease Patient Advocacy Day; Notice of Meeting

Science.gov (United States)

2011-12-20

... Administration, HHS. ACTION: Notice. The Food and Drug Administration's (FDA) Office of Orphan Products... educate the rare disease community on the FDA regulatory processes. This educational meeting will consist...

Towards a Computable Data Corpus of Temporal Correlations between Drug Administration and Lab Value Changes.

Directory of Open Access Journals (Sweden)

Axel Newe

Full Text Available The analysis of electronic health records for an automated detection of adverse drug reactions is an approach to solve the problems that arise from traditional methods like spontaneous reporting or manual chart review. Algorithms addressing this task should be modeled on the criteria for a standardized case causality assessment defined by the World Health Organization. One of these criteria is the temporal relationship between drug intake and the occurrence of a reaction or a laboratory test abnormality. Appropriate data that would allow for developing or validating related algorithms is not publicly available, though.In order to provide such data, retrospective routine data of drug administrations and temporally corresponding laboratory observations from a university clinic were extracted, transformed and evaluated by experts in terms of a reasonable time relationship between drug administration and lab value alteration.The result is a data corpus of 400 episodes of normalized laboratory parameter values in temporal context with drug administrations. Each episode has been manually classified whether it contains data that might indicate a temporal correlation between the drug administration and the change of the lab value course, whether such a change is not observable or whether a decision between those two options is not possible due to the data. In addition, each episode has been assigned a concordance value which indicates how difficult it is to assess. This is the first open data corpus of a computable ground truth of temporal correlations between drug administration and lab value alterations.The main purpose of this data corpus is the provision of data for further research and the provision of a ground truth which allows for comparing the outcome of other assessments of this data with the outcome of assessments made by human experts. It can serve as a contribution towards systematic, computerized ADR detection in retrospective data. With

76 FR 28688 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

Science.gov (United States)

2011-05-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 866 [Docket No. FDA-2011-D-0102] Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: In Vitro Diagnostic Devices for Bacillus Species Detection AGENCY: Food and...

Prohibited or regulated? LSD psychotherapy and the United States Food and Drug Administration.

Science.gov (United States)

Oram, Matthew

2016-09-01

Over the 1950s and early 1960s, the use of the hallucinogenic drug lysergic acid diethylamide (LSD) to facilitate psychotherapy was a promising field of psychiatric research in the USA. However, during the 1960s, research began to decline, before coming to a complete halt in the mid-1970s. This has commonly been explained through the increase in prohibitive federal regulations during the 1960s that aimed to curb the growing recreational use of the drug. However, closely examining the Food and Drug Administration's regulation of LSD research in the 1960s will reveal that not only was LSD research never prohibited, but that the administration supported research to a greater degree than has been recognized. Instead, the decline in research reflected more complex changes in the regulation of pharmaceutical research and development. © The Author(s) 2016.

76 FR 64354 - Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small...

Science.gov (United States)

2011-10-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0529] Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small Business... amounts on small business, as set forth in the FDA Food Safety Modernization Act (FSMA). In particular...

76 FR 45818 - Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small...

Science.gov (United States)

2011-08-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0529] Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small Business... burden of fee amounts on small business, as set forth in the FDA Food Safety Modernization Act (FSMA...

DILEMMAS OF COMMUNITY-DIRECTED MASS DRUG ADMINISTRATION FOR LYMPHATIC FILARIASIS CONTROL

DEFF Research Database (Denmark)

Kisoka, William; Mushi, Declare; Meyrowitsch, Dan W.

2017-01-01

There has in recent years been a growing interest in the social significance of global health policy and associated interventions. This paper is concerned with neglected tropical disease control, which prescribes annual mass drug administration to interrupt transmission of, among others, lymphati...

Modeling of corneal and retinal pharmacokinetics after periocular drug administration.

Science.gov (United States)

Amrite, Aniruddha C; Edelhauser, Henry F; Kompella, Uday B

2008-01-01

the SD rat corneas. Similar pharmacokinetics models explain drug delivery to the cornea in rat and rabbit animal models. Retinal pharmacokinetics after periocular drug administration can be explained with a four-compartment (periocular space, choroid-containing transfer compartment, retina, and distribution compartment) model with elimination from the periocular space, retina, and choroid compartment. Inclusion of a dissolution-release step before the drug is available for absorption or elimination better explains retinal t(max). Good fits were obtained in both the BN (r = 0.99) and SD (r = 0.99) rats for retinal celecoxib using the same model; however, the parameter estimates differed. Corneal and retinal pharmacokinetics of small lipophilic molecules after periocular administration can be described by compartment models. The modeling analysis shows that (1) leak-back from the site of administration most likely contributes to the apparent lack of an increase phase in corneal concentrations; (2) elimination via the conjunctival or periocular blood and lymphatic systems contributes significantly to drug clearance after periocular injection; (3) corneal pharmacokinetics of small lipophilic molecules can be explained by using similar models in rats and rabbits; and (4) although there are differences in some retinal pharmacokinetics parameters between the pigmented and nonpigmented rats, the physiological basis of these differences has yet to be ascertained.

77 FR 20825 - Guidance for Industry and Food and Drug Administration Staff; User Fees for 513(g) Requests for...

Science.gov (United States)

2012-04-06

...] Guidance for Industry and Food and Drug Administration Staff; User Fees for 513(g) Requests for Information... Administration (FDA) is announcing the availability of the guidance entitled ``Guidance for Industry and Food and... ``Guidance for Industry and Food and Drug Administration Staff; User Fees for 513(g) Requests for Information...

Anesthesia in the patient with multiple drug allergies: are all allergies the same?

Science.gov (United States)

Dewachter, Pascale; Mouton-Faivre, Claudie; Castells, Mariana C; Hepner, David L

2011-06-01

During the preoperative evaluation, patients frequently indicate 'multiple drug allergies', most of which have not been validated. Potential allergic cross-reactivity between drugs and foods is frequently considered as a risk factor for perioperative hypersensitivity. The aim of this review is to facilitate the recognition of risk factors for perioperative anaphylaxis and help the management of patients with 'multiple drug allergies' during the perioperative period. Neuromuscular blocking agents (NMBAs) and antibiotics are the most common drugs triggering perioperative anaphylaxis. Quaternary ammonium ions have been suggested to be the allergenic determinant of NMBAs. Even though the 'pholcodine hypothesis' has been suggested to explain the occurrence of NMBA-induced allergy, this concept remains unclear. Although many practitioners believe that certain food allergies present an issue with the use of propofol, there is no role to contraindicate propofol in egg-allergic, soy-allergic or peanut-allergic patients. IgE-mediated hypersensitivity has been reported with seafood and iodinated drugs, IgE-mediated hypersensitivity has been reported with seafood and iodinated drugs, but there is no cross-reactivity between them. The allergenic determinants have been characterized for fish, shellfish and povidone iodine and remain unknown for contrast agents. There are many false assumptions regarding drug allergies. The main goal of this article is to review the potential cross-reactivity among specific families of drugs and foods in order to facilitate the anesthetic management of patients with 'multiple drug allergies'.

Best practice strategies to safeguard drug prescribing and drug administration: an anthology of expert views and opinions.

Science.gov (United States)

Seidling, Hanna M; Stützle, Marion; Hoppe-Tichy, Torsten; Allenet, Benoît; Bedouch, Pierrick; Bonnabry, Pascal; Coleman, Jamie J; Fernandez-Llimos, Fernando; Lovis, Christian; Rei, Maria Jose; Störzinger, Dominic; Taylor, Lenka A; Pontefract, Sarah K; van den Bemt, Patricia M L A; van der Sijs, Heleen; Haefeli, Walter E

2016-04-01

While evidence on implementation of medication safety strategies is increasing, reasons for selecting and relinquishing distinct strategies and details on implementation are typically not shared in published literature. We aimed to collect and structure expert information resulting from implementing medication safety strategies to provide advice for decision-makers. Medication safety experts with clinical expertise from thirteen hospitals throughout twelve European and North American countries shared their experience in workshop meetings, on-site-visits and remote structured interviews. We performed an expert-based, in-depth assessment of implementation of best-practice strategies to improve drug prescribing and drug administration. Workflow, variability and recommended medication safety strategies in drug prescribing and drug administration processes. According to the experts, institutions chose strategies that targeted process steps known to be particularly error-prone in the respective setting. Often, the selection was channeled by local constraints such as the e-health equipment and critically modulated by national context factors. In our study, the experts favored electronic prescribing with clinical decision support and medication reconciliation as most promising interventions. They agreed that self-assessment and introduction of medication safety boards were crucial to satisfy the setting-specific differences and foster successful implementation. While general evidence for implementation of strategies to improve medication safety exists, successful selection and adaptation of a distinct strategy requires a thorough knowledge of the institute-specific constraints and an ongoing monitoring and adjustment of the implemented measures.

Rational polypharmacology: systematically identifying and engaging multiple drug targets to promote axon growth

Science.gov (United States)

Al-Ali, Hassan; Lee, Do-Hun; Danzi, Matt C.; Nassif, Houssam; Gautam, Prson; Wennerberg, Krister; Zuercher, Bill; Drewry, David H.; Lee, Jae K.; Lemmon, Vance P.; Bixby, John L.

2016-01-01

Mammalian Central Nervous System (CNS) neurons regrow their axons poorly following injury, resulting in irreversible functional losses. Identifying therapeutics that encourage CNS axon repair has been difficult, in part because multiple etiologies underlie this regenerative failure. This suggests a particular need for drugs that engage multiple molecular targets. Although multi-target drugs are generally more effective than highly selective alternatives, we lack systematic methods for discovering such drugs. Target-based screening is an efficient technique for identifying potent modulators of individual targets. In contrast, phenotypic screening can identify drugs with multiple targets; however, these targets remain unknown. To address this gap, we combined the two drug discovery approaches using machine learning and information theory. We screened compounds in a phenotypic assay with primary CNS neurons and also in a panel of kinase enzyme assays. We used learning algorithms to relate the compounds’ kinase inhibition profiles to their influence on neurite outgrowth. This allowed us to identify kinases that may serve as targets for promoting neurite outgrowth, as well as others whose targeting should be avoided. We found that compounds that inhibit multiple targets (polypharmacology) promote robust neurite outgrowth in vitro. One compound with exemplary polypharmacology, was found to promote axon growth in a rodent spinal cord injury model. A more general applicability of our approach is suggested by its ability to deconvolve known targets for a breast cancer cell line, as well as targets recently shown to mediate drug resistance. PMID:26056718

78 FR 9928 - Food and Drug Administration Drug Shortages Task Force and Strategic Plan; Request for Comments

Science.gov (United States)

2013-02-12

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0124... metrics. With that in mind, FDA would like input on the following issues: What metrics do manufacturers... been suggested as a potentially useful approach to expanding manufacturing capacity and preventing...

FDA publishes conflict of interest rules for clinical trials. Food and Drug Administration.

Science.gov (United States)

James, J S

1998-03-06

The Food and Drug Administration (FDA) published new rules defining conflict of interests between drug companies and medical researchers and clinicians. Certain financial arrangements will need to be disclosed, although the FDA estimates that only one to ten percent of pharmaceutical companies will need to submit disclosures for one or more of their investigators. The purpose of the new rule is to prevent bias in safety and efficacy studies of drugs and medical devices. The full rule is published in the Federal Register.

75 FR 69449 - Draft Guidance for Industry and Food and Drug Administration Staff on Dear Health Care Provider...

Science.gov (United States)

2010-11-12

... annually from approximately 25 application holders. FDA professionals familiar with Dear Health Care... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0319] Draft Guidance for Industry and Food and Drug Administration Staff on Dear Health Care Provider Letters...

Effects of chronic administration of drugs of abuse on impulsive choice (delay discounting) in animal models.

Science.gov (United States)

Setlow, Barry; Mendez, Ian A; Mitchell, Marci R; Simon, Nicholas W

2009-09-01

Drug-addicted individuals show high levels of impulsive choice, characterized by preference for small immediate over larger but delayed rewards. Although the causal relationship between chronic drug use and elevated impulsive choice in humans has been unclear, a small but growing body of literature over the past decade has shown that chronic drug administration in animal models can cause increases in impulsive choice, suggesting that a similar causal relationship may exist in human drug users. This article reviews this literature, with a particular focus on the effects of chronic cocaine administration, which have been most thoroughly characterized. The potential mechanisms of these effects are described in terms of drug-induced neural alterations in ventral striatal and prefrontal cortical brain systems. Some implications of this research for pharmacological treatment of drug-induced increases in impulsive choice are discussed, along with suggestions for future research in this area.

Drug administration errors in an institution for individuals with intellectual disability : an observational study

NARCIS (Netherlands)

van den Bemt, P M L A; Robertz, R; de Jong, A L; van Roon, E N; Leufkens, H G M

BACKGROUND: Medication errors can result in harm, unless barriers to prevent them are present. Drug administration errors are less likely to be prevented, because they occur in the last stage of the drug distribution process. This is especially the case in non-alert patients, as patients often form

Acute antidepressant drug administration and autobiographical memory recall

DEFF Research Database (Denmark)

Papadatou-Pastou, Marietta; Miskowiak, Kamilla W; Williams, J Mark G

2012-01-01

Antidepressants affect memory and neural responses to emotionally valenced stimuli in healthy volunteers. However, it is unclear whether this extends to autobiographical memory for personally experienced events. The current study investigated the effects of acute administration of the antidepress...... of reboxetine on emotional memory extends to recall of personally experienced events. Such effects may be relevant to the cognitive improvements found with recovery from depression and with the mechanism of action of contemporary antidepressant drugs.......Antidepressants affect memory and neural responses to emotionally valenced stimuli in healthy volunteers. However, it is unclear whether this extends to autobiographical memory for personally experienced events. The current study investigated the effects of acute administration...... in the processing of positive versus negative memories was reduced following reboxetine compared with placebo in the left frontal lobe (extending into the insula) and the right superior temporal gyrus. This was paired with increased memory speed in volunteers given reboxetine versus placebo. The effect...

5-FU Metabolism in Cancer and Orally-Administrable 5-FU Drugs

Directory of Open Access Journals (Sweden)

Iwao Sasaki

2010-09-01

Full Text Available 5-Fluorouracil (5-FU is a key anticancer drug that for its broad antitumor activity, as well as for its synergism with other anticancer drugs, has been used to treat various types of malignancies. In chemotherapeutic regimens, 5-FU has been combined with oxaliplatin, irinotecan and other drugs as a continuous intravenous infusion. Recent clinical chemotherapy studies have shown that several of the regimens with oral 5-FU drugs are not inferior compared to those involving continuous 5-FU infusion chemotherapy, and it is probable that in some regimens continuous 5-FU infusion can be replaced by oral 5-FU drugs. Historically, both the pharmaceutical industry and academia in Japan have been involved in the development of oral 5-FU drugs, and this review will focus on the current knowledge of 5-FU anabolism and catabolism, and the available information about the various orally-administrable 5-FU drugs, including UFT, S-1 and capecitabine. Clinical studies comparing the efficacy and adverse events of S-1 and capecitabine have been reported, and the accumulated results should be utilized to optimize the treatment of cancer patients. On the other hand, it is essential to elucidate the pharmacokinetic mechanism of each of the newly-developed drugs, to correctly select the drugs for each patient in the clinical setting, and to further develop optimized drug derivatives.

21 CFR 20.105 - Testing and research conducted by or with funds provided by the Food and Drug Administration.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Testing and research conducted by or with funds... Categories of Records § 20.105 Testing and research conducted by or with funds provided by the Food and Drug Administration. (a) Any list that may be prepared by the Food and Drug Administration of testing and research...

The 2015 US Food and Drug Administration Pregnancy and Lactation Labeling Rule.

Science.gov (United States)

Brucker, Mary C; King, Tekoa L

2017-05-01

As of 2015, the US Food and Drug Administration (FDA) discontinued the pregnancy risk categories (ABCDX) that had been used to denote the putative safety of drugs for use among pregnant women. The ABCDX system has been replaced by the FDA Pregnancy and Lactation Labeling Rule (PLLR) that requires narrative text to describe risk information, clinical considerations, and background data for the drug. The new rule includes 3 overarching categories: 1) pregnancy, which includes labor and birth; 2) lactation; and 3) females and males of reproductive potential. This article reviews the key components of the PLLR and clinical implications, and provides resources for clinicians who prescribe drugs for women of reproductive age. © 2017 by the American College of Nurse-Midwives.

Prospects for the control of neglected tropical diseases by mass drug administration

NARCIS (Netherlands)

Smits, Henk L.

2009-01-01

The prospects for the control of neglected tropical diseases, including soil-transmitted helminthiasis, shistosomiasis, lymphatic filariasis, onchocerciasis and trachoma, through mass drug administration, are exemplified by the elimination of the trachoma as a public-health problem in Morocco. In

[New drugs in the treatment of multiple myeloma].

Science.gov (United States)

Oriol, Albert; Motlló, Cristina

2014-09-15

Progress in the treatment of multiple myeloma in the last decade has been able to delay, but ultimately not to prevent, the development of resistances and most patients still die of the disease or its related complications. New drugs have been developed including new alkylating agents, proteasome inhibitors and immunomodulators but also monoclonal antibodies and drugs with new mechanisms of action. Hopefully, this new generation of targeted agents will improve the results of the initial therapy, avoid relapses and development of resistances and provide better and less toxic options for the relapsed and refractory patient. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Salvage Therapy of Multiple Myeloma: The New Generation Drugs

Directory of Open Access Journals (Sweden)

Alessandra Romano

2014-01-01

Full Text Available During the past decade, overall results of treatment of multiple myeloma (MM have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs. However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and therapeutic strategies are required for continued disease control. In this review, we summarize new insights in salvage therapy for relapsed/refractory MM as emerging from recent clinical trials exploring the activity of bendamustine, new generation proteasome inhibitors, novel IMiDs, monoclonal antibodies, and drugs interfering with growth pathways.

Salvage Therapy of Multiple Myeloma: The New Generation Drugs

Science.gov (United States)

Romano, Alessandra; Conticello, Concetta; Di Raimondo, Cosimo; Schinocca, Elena; La Fauci, Alessia; Parrinello, Nunziatina Laura; Chiarenza, Annalisa

2014-01-01

During the past decade, overall results of treatment of multiple myeloma (MM) have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs). However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and therapeutic strategies are required for continued disease control. In this review, we summarize new insights in salvage therapy for relapsed/refractory MM as emerging from recent clinical trials exploring the activity of bendamustine, new generation proteasome inhibitors, novel IMiDs, monoclonal antibodies, and drugs interfering with growth pathways. PMID:24967371

[Drug administration to pediatric patients: Evaluation of the nurses' preparation habits in pediatric units].

Science.gov (United States)

Ménétré, S; Weber, M; Socha, M; Le Tacon, S; May, I; Schweitzer, C; Demoré, B

2018-04-01

In hospitals, the nursing staff is often confronted with the problem of the preparation and administration of drugs for their pediatric patients because of the lack of indication, pediatric dosage, and appropriate galenic form. The goal of this study was to give an overview of the nurses' preparation habits in pediatric units and highlight their daily problems. This single-center prospective study was conducted through an observation of the nursing staff during the drug preparation process in medicine, surgery and intensive care units. We included 91 patients (55 boys and 36 girls), with an average age of 6.3 years (youngest child, 10 days old; oldest child, 18 years old). We observed a mean 2.16 drug preparations per patient [1-5]. We collected 197 observation reports regarding 66 injectable drugs and 131 oral drugs (71 liquid forms and 60 solid forms). The majority of these reports concerned central nervous system drugs (63/197), metabolism and digestive system drugs (50/197), and anti-infective drugs (46/197). The study highlights the nurses' difficulties: modification of the solid galenic forms, lack of knowledge on oral liquid form preservation or reconstitution methods, withdrawal of small volumes, and vague and noncompliant labeling. This study led to the creation of a specific working group for pediatrics. This multidisciplinary team meets on a regular basis to work toward improving the current habits to both simplify and secure drug administration to hospitalized children. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Transdermal and Topical Drug Administration in the Treatment of Pain

Directory of Open Access Journals (Sweden)

Wojciech Leppert

2018-03-01

Full Text Available The comprehensive treatment of pain is multidimodal, with pharmacotherapy playing a key role. An effective therapy for pain depends on the intensity and type of pain, the patients’ age, comorbidities, and appropriate choice of analgesic, its dose and route of administration. This review is aimed at presenting current knowledge on analgesics administered by transdermal and topical routes for physicians, nurses, pharmacists, and other health care professionals dealing with patients suffering from pain. Analgesics administered transdermally or topically act through different mechanisms. Opioids administered transdermally are absorbed into vessels located in subcutaneous tissue and, subsequently, are conveyed in the blood to opioid receptors localized in the central and peripheral nervous system. Non–steroidal anti–inflammatory drugs (NSAIDs applied topically render analgesia mainly through a high concentration in the structures of the joint and a provision of local anti–inflammatory effects. Topically administered drugs such as lidocaine and capsaicin in patches, capsaicin in cream, EMLA cream, and creams containing antidepressants (i.e., doxepin, amitriptyline act mainly locally in tissues through receptors and/or ion channels. Transdermal and topical routes offer some advantages over systemic analgesic administration. Analgesics administered topically have a much better profile for adverse effects as they relieve local pain with minimal systemic effects. The transdermal route apart from the above-mentioned advantages and provision of long period of analgesia may be more convenient, especially for patients who are unable to take drugs orally. Topically and transdermally administered opioids are characterised by a lower risk of addiction compared to oral and parenteral routes.

Lipid nanoparticles for administration of poorly water soluble neuroactive drugs.

Science.gov (United States)

Esposito, Elisabetta; Drechsler, Markus; Mariani, Paolo; Carducci, Federica; Servadio, Michela; Melancia, Francesca; Ratano, Patrizia; Campolongo, Patrizia; Trezza, Viviana; Cortesi, Rita; Nastruzzi, Claudio

2017-09-01

This study describes the potential of solid lipid nanoparticles and nanostructured lipid carriers as nano-formulations to administer to the central nervous system poorly water soluble drugs. Different neuroactive drugs, i.e. dimethylfumarate, retinyl palmitate, progesterone and the endocannabinoid hydrolysis inhibitor URB597 have been studied. Lipid nanoparticles constituted of tristearin or tristearin in association with gliceryl monoolein were produced. The nanoencapsulation strategy allowed to obtain biocompatible and non-toxic vehicles, able to increase the solubility of the considered neuroactive drugs. To improve URB597 targeting to the brain, stealth nanoparticles were produced modifying the SLN surface with polysorbate 80. A behavioural study was conducted in rats to test the ability of SLN containing URB597 given by intranasal administration to alter behaviours relevant to psychiatric disorders. URB597 maintained its activity after nanoencapsulation, suggesting the possibility to propose this kind of vehicle as alternative to unphysiological mixtures usually employed for animal and clinical studies.

Rethinking the Food and Drug Administration's 2013 guidance on developing drugs for early-stage Alzheimer's disease.

Science.gov (United States)

Schneider, Lon S

2014-03-01

The February 2013 Food and Drug Administration (FDA) draft guidance for developing drugs for early-stage Alzheimer's disease (AD) creates certain challenges as they guide toward the use of one cognitive outcome to gain accelerated marketing approval for preclinical AD drugs, and a composite clinical scale - the Clinical Dementia Rating Scale in particular - for the primary outcome for prodromal AD clinical trials. In light of the developing knowledge regarding early stage diagnoses and clinical trials outcomes, we recommend that FDA describe its requirements for validating preclinical AD diagnoses for drug development purposes, maintain the principle for requiring coprimary outcomes, and encourage the advancement of outcomes for early stage AD trials. The principles for drug development for early stage AD should not differ from those for clinical AD, especially as the diagnoses of prodromal and early AD impinge on each other. The FDA should not recommend that a composite scale be used as a sole primary efficacy outcome to support a marketing claim unless it requires that the cognitive and functional components of such a scale are demonstrated to be individually meaningful. The current draft guidelines may inadvertently constrain efforts to better assess the clinical effects of new drugs and inhibit innovation in an area where evidence-based clinical research practices are still evolving. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Sleep loss and acute drug abuse can induce DNA damage in multiple organs of mice.

Science.gov (United States)

Alvarenga, T A; Ribeiro, D A; Araujo, P; Hirotsu, C; Mazaro-Costa, R; Costa, J L; Battisti, M C; Tufik, S; Andersen, M L

2011-09-01

The purpose of the present study was to characterize the genetic damage induced by paradoxical sleep deprivation (PSD) in combination with cocaine or ecstasy (3,4-methylenedioxymethamphetamine; MDMA) in multiple organs of male mice using the single cell gel (comet) assay. C57BL/6J mice were submitted to PSD by the platform technique for 72 hours, followed by drug administration and evaluation of DNA damage in peripheral blood, liver and brain tissues. Cocaine was able to induce genetic damage in the blood, brain and liver cells of sleep-deprived mice at the majority of the doses evaluated. Ecstasy also induced increased DNA migration in peripheral blood cells for all concentrations tested. Analysis of damaged cells by the tail moment data suggests that ecstasy is a genotoxic chemical at the highest concentrations tested, inducing damage in liver or brain cells after sleep deprivation in mice. Taken together, our results suggest that cocaine and ecstasy/MDMA act as potent genotoxins in multiple organs of mice when associated with sleep loss.

Dramatyping: a generic algorithm for detecting reasonable temporal correlations between drug administration and lab value alterations

Directory of Open Access Journals (Sweden)

Axel Newe

2016-03-01

Full Text Available According to the World Health Organization, one of the criteria for the standardized assessment of case causality in adverse drug reactions is the temporal relationship between the intake of a drug and the occurrence of a reaction or a laboratory test abnormality. This article presents and describes an algorithm for the detection of a reasonable temporal correlation between the administration of a drug and the alteration of a laboratory value course. The algorithm is designed to process normalized lab values and is therefore universally applicable. It has a sensitivity of 0.932 for the detection of lab value courses that show changes in temporal correlation with the administration of a drug and it has a specificity of 0.967 for the detection of lab value courses that show no changes. Therefore, the algorithm is appropriate to screen the data of electronic health records and to support human experts in revealing adverse drug reactions. A reference implementation in Python programming language is available.

Risk of Clinically Relevant Pharmacokinetic-based Drug-drug Interactions with Drugs Approved by the U.S. Food and Drug Administration Between 2013 and 2016.

Science.gov (United States)

Yu, Jingjing; Zhou, Zhu; Tay-Sontheimer, Jessica; Levy, Rene H; Ragueneau-Majlessi, Isabelle

2018-03-23

A total of 103 drugs (including 14 combination drugs) were approved by the U.S. Food and Drug Administration from 2013 to 2016. Pharmacokinetic-based drug interaction profiles were analyzed using the University of Washington Drug Interaction Database and the clinical relevance of these observations was characterized based on information from New Drug Application reviews. CYP3A was identified as a major contributor to clinical drug-drug interactions (DDIs), involved in approximately 2/3 of all interactions. Transporters (alone or with enzymes) were found to participate in about half of all interactions, although most of these were weak-to-moderate interactions. When considered as victims, eight new molecular entities (NMEs; cobimetinib, ibrutnib, isavuconazole, ivabradine, naloxegol, paritaprevir, simeprevir, and venetoclax) were identified as sensitive substrates of CYP3A, two NMEs (pirfenidone and tasimelteon) were sensitive substrates of CYP1A2, one NME (dasabuvir) was a sensitive substrate of CYP2C8, one NME (eliglustat) was a sensitive substrate of CYP2D6, and one NME (grazoprevir) was a sensitive substrate of OATP1B1/3 (with changes in exposure greater than 5-fold when co-administered with a strong inhibitor). Interestingly, approximately 75% of identified CYP3A substrates were also substrates of P-gp. As perpetrators, most clinical DDIs involved weak-to-moderate inhibition or induction, with only two drugs (Viekira Pak and idelalisib) showing strong inhibition of CYP3A, and one NME (lumacaftor) considered as a strong CYP3A inducer. Among drugs with large changes in exposure (≥ 5-fold), whether as victim or perpetrator, the most represented therapeutic classes were antivirals and oncology drugs, suggesting a significant risk of clinical DDIs in these patient populations. The American Society for Pharmacology and Experimental Therapeutics.

Design of a RESTful web information system for drug prescription and administration.

Science.gov (United States)

Bianchi, Lorenzo; Paganelli, Federica; Pettenati, Maria Chiara; Turchi, Stefano; Ciofi, Lucia; Iadanza, Ernesto; Giuli, Dino

2014-05-01

Drug prescription and administration processes strongly impact on the occurrence of risks in medical settings for they can be sources of adverse drug events (ADEs). A properly engineered use of information and communication technologies has proven to be a promising approach to reduce these risks. In this study, we propose PHARMA, a web information system which supports healthcare staff in the secure cooperative execution of drug prescription, transcription and registration tasks. PHARMA allows the easy sharing and management of documents containing drug-related information (i.e., drug prescriptions, medical reports, screening), which is often inconsistent and scattered across different information systems and heterogeneous organization domains (e.g., departments, other hospital facilities). PHARMA enables users to access such information in a consistent and secure way, through the adoption of REST and web-oriented design paradigms and protocols. We describe the implementation of the PHARMA prototype, and we discuss the results of the usability evaluation that we carried out with the staff of a hospital in Florence, Italy.

78 FR 54901 - Food and Drug Administration/American Academy of Ophthalmology Workshop on Developing Novel...

Science.gov (United States)

2013-09-06

.... Food and beverages will be available for purchase by participants during the workshop breaks. If you....regulations.gov . It may be viewed at the Division of Dockets Management (HFA-305), Food and Drug... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001...

The history and contemporary challenges of the US Food and Drug Administration.

Science.gov (United States)

Borchers, Andrea T; Hagie, Frank; Keen, Carl L; Gershwin, M Eric

2007-01-01

The year 2006 marks the 100th anniversary of the regulatory agency now known as the US Food and Drug Administration (FDA), the first consumer protection agency of the federal government and arguably the most influential regulatory agency in the world. The FDA thus plays an integral role in the use of pharmaceuticals, not only in the United States but worldwide. The goal of this review was to present an overview of the FDA and place its current role in the perspectives of history and contemporary needs. Relevant materials for this review were identified through a search of the English-language literature indexed on MEDLINE (through 2006) using the main search terms United States Food and Drug Administration, FDA, history of the FDA, drug approvals, drug legislation, and FDA legislation. Results from the initial searches were then explored further. The statute that created the bureau which later became the FDA established this agency to prohibit interstate commerce of adulterated foods, drinks, and drugs. The Food, Drug, and Cosmetic Act that replaced it in 1938, and subsequent food and drug laws and amendments, expanded the FDA's responsibilities to cosmetics, medical devices, biological products, and radiation-emitting products. These amendments have also established the FDA as a mainly preventive regulatory agency that relies chiefly on pre-market control. As such, the FDA has played an important role in shaping the modern pharmaceutical industry by making the scientific approach and the clinical trial process the standard for establishing safety and efficacy and by making rigorous scientific analysis the predominant component of the process for pharmaceutical regulation. As shown in this review, the evolution of the FDA can be described as a series of "crisis-legislation-adaptation" cycles: a public health crisis promoted the passage of congressional legislation, which was then followed by implementation of the law by the FDA. However, the crises the FDA faces

[Professional practice evaluation of injectable drug preparation and administration in neonatology].

Science.gov (United States)

Morin, P; Guillois, B; Gloanec, L; Chatelier, N; Saint-Lorant, G

2017-09-01

Adverse drug events are a daily concern in neonatology departments. The aim of this study was to assess the professional practices of preparation and administration of injectable forms of medications in neonatology. A professional practice evaluation with regard to the preparation and administration of various injectable forms of medications in different neonatology units within a given department was conducted by a pharmacy intern based on an assessment grid comprising ten criteria. Following an initial assessment, the results were presented to the care team, which validated the corrective measures put forward by a multiprofessional work group. A second assessment was conducted following the same methodology. Fifty of the department's 76 pediatric nurses were assessed during the first round of the audit and 21 during the second round. Two improvement priorities were identified: taking account of the dead volume of medication in needles and syringe hubs, together with complete identification of syringes used to administer medication. During the second round, these two aspects were improved, progressing from 38% to 100% and from 59% to 89%, respectively. To improve drug administration in neonatology and consequently, to improve patient safety, professional practice evaluation is an essential tool that requires close collaboration between the paramedical team, physicians and pharmacists. Its main value lies in the mobilization of the entire team around the subject in question, hence generating improved understanding and application of corrective measures. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Impact of repeated intravenous cocaine administration on incentive motivation depends on mode of drug delivery.

Science.gov (United States)

LeBlanc, Kimberly H; Maidment, Nigel T; Ostlund, Sean B

2014-11-01

The incentive sensitization theory of addiction posits that repeated exposure to drugs of abuse, like cocaine, can lead to long-term adaptations in the neural circuits that support motivated behavior, providing an account of pathological drug-seeking behavior. Although pre-clinical findings provide strong support for this theory, much remains unknown about the conditions that support incentive sensitization. The current study examined whether the mode of cocaine administration is an important factor governing that drug's long-term impact on behavior. Separate groups of rats were allowed either to self-administer intravenous cocaine or were given an equivalent number and distribution of unsignaled cocaine or saline infusions. During the subsequent test of incentive motivation (Pavlovian-to-instrumental transfer), we found that rats with a history of cocaine self-administration showed strong cue-evoked food seeking, in contrast to rats given unsignaled cocaine or saline. This finding indicates that the manner in which cocaine is administered can determine its lasting behavioral effects, suggesting that subjective experiences during drug use play a critical role in the addiction process. Our findings may therefore have important implications for the study and treatment of compulsive drug seeking. © 2013 Society for the Study of Addiction.

Poly-ε-caprolactone microspheres as a drug delivery system for cannabinoid administration: development, characterization and in vitro evaluation of their antitumoral efficacy.

Science.gov (United States)

Hernán Pérez de la Ossa, D; Ligresti, A; Gil-Alegre, M E; Aberturas, M R; Molpeceres, J; Di Marzo, V; Torres Suárez, A I

2012-08-10

Cannabinoids show promise for the treatment of various medical conditions such as emesis, anorexia, pain, cancer, multiple sclerosis, Parkinson's disease and glaucoma. However, their high lipohilicity and instability complicate their handling and dosing, and restrict their use as pharmaceuticals. The objective of the present work was to assess the feasibility of developing cannabinoid loaded poly-ε-caprolactone (PCL) microparticles prepared by the oil-in-water emulsion-solvent evaporation technique as a suitable dosage form for their administration. Spherical microparticles with a size range of 20-50 μm, and high entrapment efficiency (around 100%) were obtained. Cannabidiol (CBD) dissolved in the polymeric matrix of the microspheres was slowly released in vitro within 10 days. In vitro cell viability studies demonstrated the antitumoral activity of CBD released from microparticles. After 4 and 7 days of incubation, CBD in microspheres significantly inhibited the growth of MDA-MB-231 cells by 60% as compared to the 50% attained with free drug. The results suggest that PCL microparticles could be an alternative delivery system for long-term cannabinoid administration, showing potential therapeutic advantages over free drug. Copyright © 2012 Elsevier B.V. All rights reserved.

Drug induced mortality: a multiple cause approach on Italian causes of death Register

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Francesco Grippo

2015-04-01

Full Text Available Background: Drug-related mortality is a complex phenomenon that has several health, social and economic effects. In this paper trends of drug-induced mortality in Italy are analysed. Two approaches have been followed: the traditional analysis of the underlying cause of death (UC (data refers to the Istat mortality database from 1980 to 2011, and the multiple cause (MCanalysis, that is the analysis of all conditions reported on the death certificate (data for 2003-2011 period.Methods: Data presented in this paper are based on the Italian mortality register. The selection of Icd codes used for the analysis follows the definition of the European Monitoring Centre for Drugs and Drug Addiction. Using different indicators (crude and standardized rates, ratio multiple to underlying, the results obtained from the two approaches (UC and MC have been compared. Moreover, as a measure of association between drug-related causes and specific conditions on the death certificate, an estimation of the age-standardized relative risk (RR has been used.Results: In the years 2009-2011, the total number of certificates whit mention of drug use was 1,293, 60% higher than the number UC based. The groups of conditions more strongly associated with drug-related causes are the mental and behavioral disorders (especially alcohol consumption, viral hepatitis, cirrhosis and fibrosis of liver, AIDS and endocarditis.Conclusions : The analysis based on multiple cause approach shows, for the first time, a more detailed picture of the drug related death; it allows to better describe the mortality profiles and to re-evaluate  the contribution of a specific cause to death.

Multiple Measures of Outcome in Assessing a Prison-Based Drug Treatment Program

Science.gov (United States)

Prendergast, Michael L.; Hall, Elizabeth A.; Wexler, Harry K.

2003-01-01

Evaluations of prison-based drug treatment programs typically focus on one or two dichotomous outcome variables related to recidivism. In contrast, this paper uses multiple measures of outcomes related to crime and drug use to examine the impact of prison treatment. Crime variables included self-report data of time to first illegal activity,…

A new minimal-stress freely-moving rat model for preclinical studies on intranasal administration of CNS drugs.

Science.gov (United States)

Stevens, Jasper; Suidgeest, Ernst; van der Graaf, Piet Hein; Danhof, Meindert; de Lange, Elizabeth C M

2009-08-01

To develop a new minimal-stress model for intranasal administration in freely moving rats and to evaluate in this model the brain distribution of acetaminophen following intranasal versus intravenous administration. Male Wistar rats received one intranasal cannula, an intra-cerebral microdialysis probe, and two blood cannulas for drug administration and serial blood sampling respectively. To evaluate this novel model, the following experiments were conducted. 1) Evans Blue was administered to verify the selectivity of intranasal exposure. 2) During a 1 min infusion 10, 20, or 40 microl saline was administered intranasally or 250 microl intravenously. Corticosterone plasma concentrations over time were compared as biomarkers for stress. 3) 200 microg of the model drug acetaminophen was given in identical setup and plasma, and brain pharmacokinetics were determined. In 96% of the rats, only the targeted nasal cavity was deeply colored. Corticosterone plasma concentrations were not influenced, neither by route nor volume of administration. Pharmacokinetics of acetaminophen were identical after intravenous and intranasal administration, although the Cmax in microdialysates was reached a little earlier following intravenous administration. A new minimal-stress model for intranasal administration in freely moving rats has been successfully developed and allows direct comparison with intravenous administration.

Transmission assessment surveys (TAS) to define endpoints for lymphatic filariasis mass drug administration

DEFF Research Database (Denmark)

Chu, Brian K.; Deming, Michael; Biritwum, Nana-Kwadwo

2013-01-01

Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached...

77 FR 10753 - Draft Guidance for Industry: Food and Drug Administration Records Access Authority Under the...

Science.gov (United States)

2012-02-23

...] Draft Guidance for Industry: Food and Drug Administration Records Access Authority Under the Federal... industry entitled ``FDA Records Access Authority Under Sections 414 and 704 of the Federal Food, Drug...). This updated draft guidance is intended to provide individuals in the human and animal food industries...

Repeated intermittent administration of psychomotor stimulant drugs alters the acquisition of Pavlovian approach behavior in rats: differential effects of cocaine, d-amphetamine and 3,4- methylenedioxymethamphetamine ("Ecstasy").

Science.gov (United States)

Taylor, J R; Jentsch, J D

2001-07-15

Psychomotor stimulant drugs can produce long-lasting changes in neurochemistry and behavior after multiple doses. In particular, neuroadaptations within corticolimbic brain structures that mediate incentive learning and motivated behavior have been demonstrated after chronic exposure to cocaine, d-amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA). As stimulus-reward learning is likely relevant to addictive behavior (i.e., augmented conditioned reward and stimulus control of behavior), we have investigated whether prior repeated administration of psychomotor stimulant drugs (of abuse, including cocaine, d-amphetamine, or MDMA, would affect the acquisition of Pavlovian approach behavior. Water-deprived rats were tested for the acquisition of Pavlovian approach behavior after 5 days treatment with cocaine (15-20 mg/kg once or twice daily), d-amphetamine (2.5 mg/kg once or twice daily), or MDMA (2.5 mg/kg twice daily) followed by a 7-day, drug-free period. Prior repeated treatment with cocaine or d-amphetamine produced a significant enhancement of acquisition of Pavlovian approach behavior, indicating accelerated stimulus-reward learning, whereas MDMA administration produced increased inappropriate responding, indicating impulsivity. Abnormal drug-induced approach behavior was found to persist throughout the testing period. These studies demonstrate that psychomotor stimulant-induced sensitization can produce long-term alterations in stimulus-reward learning and impulse control that may contribute to the compulsive drug taking that typifies addiction.

GLATIRAMER ACETATE IS A FIRST-LINE DUAL-ACTION DRUG FOR THE TREATMENT OF RELAPSING-REMITTING MULTIPLE SCLEROSIS

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T. E. Shmidt

2016-01-01

Full Text Available Multiple sclerosis (MS is the most common and potentially disabling disease of the central nervous system in young people. Not only inflammatory, but also neurodegenerative processes are involved in the pathogenesis of MS. The use of MS-modifying drugs (MSMDs  has led to a substantial reduction in the frequency of MS exacerbations and to the slower development of irreversible neurological deficit. Glatiramer acetate is one of the MSMDs of first choice and has a dual (anti-inflammatory and neuroprotective action. The drug has proven to be effective and safe if administered long-term. Therapy with glatiramer acetate has been established to promote the production of anti-inflammatory cytokines and neurotrophic factors, which prevent the development of a degenerative process and stimulate remyelination, and to slow the progression of cerebral atrophy. Experimental findings suggest that the drug improves the processes of neurogenesis.The efficiency of treatment is known to be associated with patient medication adherence. This largely depends on the frequency and route of drug administration and on the development of adverse events (AEs. To improve treatment adherence to glatiramer acetate, its new 40-mg formulation has been designed, which allows it to be administered only thrice weekly. The use of the formulation has demonstrated its efficacy and safety and resulted in a considerable reduction in the incidence rate of AEs.

Polyphosphoester nanoparticles as biodegradable platform for delivery of multiple drugs and siRNA

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Elzeny H

2017-02-01

RNA in vivo when injected intravenously in mice. Commercially available cationic polyethylenimine polymer had LD50 of ca. 61.7 mg/kg in mice, whereas no animal died after injection of the cationic PPE polymer at a dose of >130 mg/kg. Neutral PPE nanoparticles were able to encapsulate two hydrophobic drugs, namely, sorafenib and paclitaxel, which are commonly used for the treatment of hepatocellular carcinoma. Mixing the neutral and cationic PPE nanoparticles did not result in any precipitation, and the size characteristics of both types of nanoparticles were maintained. Hence, PPE polymers might have potential for the delivery of multiple drugs and diagnostic agents to diseased tissues via simple synthesis of the individual polymers and assembly into nanoparticles that can host several drugs while being mixed in the same administration set, which is of importance for industrial and clinical development. Keywords: biodegradable nanoparticles, polyphosphoester, chitosan, polyethylenimine, siRNA, sorafenib, paclitaxel

Toxicity evaluation of methoxy poly(ethylene oxide)-block-poly(ε-caprolactone) polymeric micelles following multiple oral and intraperitoneal administration to rats.

Science.gov (United States)

Binkhathlan, Ziyad; Qamar, Wajhul; Ali, Raisuddin; Kfoury, Hala; Alghonaim, Mohammed

2017-09-01

Methoxy poly(ethylene oxide)- block -poly(ɛ-caprolactone) (PEO- b -PCL) copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO- b -PCL block copolymers and assess the toxic effects of drug-free PEO- b -PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip) administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO- b -PCL micelles, sixty animals were divided into two major groups: The first group received PEO- b -PCL micelles (100 mg/kg) by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen) were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

Toxicity evaluation of methoxy poly(ethylene oxide-block-poly(ε-caprolactone polymeric micelles following multiple oral and intraperitoneal administration to rats

Directory of Open Access Journals (Sweden)

Ziyad Binkhathlan

2017-09-01

Full Text Available Methoxy poly(ethylene oxide-block-poly(ɛ-caprolactone (PEO-b-PCL copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO-b-PCL block copolymers and assess the toxic effects of drug-free PEO-b-PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO-b-PCL micelles, sixty animals were divided into two major groups: The first group received PEO-b-PCL micelles (100 mg/kg by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

Defining Persistent Hotspots: Areas That Fail to Decrease Meaningfully in Prevalence after Multiple Years of Mass Drug Administration with Praziquantel for Control of Schistosomiasis.

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Kittur, Nupur; Binder, Sue; Campbell, Carl H; King, Charles H; Kinung'hi, Safari; Olsen, Annette; Magnussen, Pascal; Colley, Daniel G

2017-12-01

Preventive chemotherapy with praziquantel for schistosomiasis morbidity control is commonly done by mass drug administration (MDA). MDA regimen is usually based on prevalence in a given area, and effectiveness is evaluated by decreases in prevalence and/or intensity of infection after several years of implementation. Multiple studies and programs now find that even within well-implemented, multiyear, annual MDA programs there often remain locations that do not decline in prevalence and/or intensity to expected levels. We term such locations "persistent hotspots." To study and address persistent hotspots, investigators and neglected tropical disease (NTD) program managers need to define them based on changes in prevalence and/or intensity. But how should the data be analyzed to define a persistent hotspot? We have analyzed a dataset from an operational research study in western Tanzania after three annual MDAs using four different approaches to define persistent hotspots. The four approaches are 1) absolute percent change in prevalence; 2) percent change in prevalence; 3) change in World Health Organization guideline categories; 4) change (absolute or percent) in both prevalence and intensity. We compare and contrast the outcomes of these analyses. Our intent is to show how the same dataset yields different numbers of persistent hotspots depending on the approach used to define them. We suggest that investigators and NTD program managers use the approach most suited for their study or program, but whichever approach is used, it should be clearly stated so that comparisons can be made within and between studies and programs.

77 FR 51698 - Authorization To Seize Property Involved in Drug Offenses for Administrative Forfeiture (2012R-9P)

Science.gov (United States)

2012-08-27

... obtained. In recognition of the link between drug trafficking and many criminal organizations, the Attorney... to combat firearm-related violent crime. The nexus between drug trafficking and firearm violence is... Involved in Drug Offenses for Administrative Forfeiture (2012R-9P) AGENCY: Department of Justice. ACTION...

Clarithromycine-Induced Ventricular Tachycardia in a Geriatric Patient Using Multiple Drugs

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Gulsah Karaoren

2016-07-01

Full Text Available Long QT syndrome is a cardiac repolarization disorder, which can be either idiopathic or congenital, and cause sudden cardiac death. The iatrogenic form is generally associated with drugs or electrolyte imbalance. Although prolonged QT interval is frequently seen due to antiarrhythmic agents, it can also be seen with antibiotics or anti-epileptics. Adverse drug interaction can manifest in several clinicopathological forms in elder individuals. In such cases, potential adverse effects of drugs used should be taken into consideration before prescribing additional drugs. Here, we present a case of clarithromycine-induced ventricular arrhythmia accompanied by QT prolongation on the third day of therapy, and the subsequent therapeutic approach, in a 91-year-old man. The patient was taking multiple drugs due to comorbid conditions and was prescribed clarithromycine therapy in the intensive care unit.

Pressure ulcers induced by drug administration: A new concept and report of four cases in elderly patients.

Science.gov (United States)

Mizokami, Fumihiro; Takahashi, Yoshiko; Hasegawa, Keiko; Hattori, Hideyuki; Nishihara, Keiji; Endo, Hidetoshi; Furuta, Katsunori; Isogai, Zenzo

2016-04-01

Drug-induced akinesia is a potential cause of pressure ulcers. However, pressure ulcers that are caused by drug-induced akinesia are not considered an adverse drug reaction (ADR). We propose that drug-induced pressure ulcers (DIPU) are pressure ulcers that are caused by an external force that is experienced after drug administration, and we considered resolution of these ulcers after drug discontinuation to be a supportive finding. In this report, we reviewed the medical records of pressure ulcer cases from a 300-bed hospital. Among 148 patients, four patients with pressure ulcers met the criterion for DIPU. In these cases, the suspected DIPU were related to treatment with olanzapine, fluvoxamine, valproic acid, clotiazepam, triazolam and rilmazafone. These drugs were administrated to manage the patients' behavioral and psychological symptoms that accompanied dementia. The DIPU in these patients were categorized as stage IV according to the National Pressure Ulcer Advisory Panel criteria. Discontinuation of the causal drugs led to significant improvements or complete healing of the pressure ulcers, and the patients subsequently recovered their mobility. Therefore, we propose that DIPU are potential ADR that have been overlooked in clinical practice. Thus, recognition of DIPU as an ADR may be important in preventing and appropriately managing pressure ulcers among elderly patients. © 2015 Japanese Dermatological Association.

Identification of Multiple Cryptococcal Fungicidal Drug Targets by Combined Gene Dosing and Drug Affinity Responsive Target Stability Screening

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Yoon-Dong Park

2016-08-01

Full Text Available Cryptococcus neoformans is a pathogenic fungus that is responsible for up to half a million cases of meningitis globally, especially in immunocompromised individuals. Common fungistatic drugs, such as fluconazole, are less toxic for patients but have low efficacy for initial therapy of the disease. Effective therapy against the disease is provided by the fungicidal drug amphotericin B; however, due to its high toxicity and the difficulty in administering its intravenous formulation, it is imperative to find new therapies targeting the fungus. The antiparasitic drug bithionol has been recently identified as having potent fungicidal activity. In this study, we used a combined gene dosing and drug affinity responsive target stability (GD-DARTS screen as well as protein modeling to identify a common drug binding site of bithionol within multiple NAD-dependent dehydrogenase drug targets. This combination genetic and proteomic method thus provides a powerful method for identifying novel fungicidal drug targets for further development.

Drug Reactions - Multiple Languages

Science.gov (United States)

... PDF Drug Interactions - HIV medicines, part 6 - English MP3 Drug Interactions - HIV medicines, part 6 - 简体中文 (Chinese, Simplified (Mandarin dialect)) MP3 Drug Interactions - HIV medicines, part 6 - English MP4 ...

Investigation of the mechanisms of action behind Electromotive Drug Administration (EMDA).

Science.gov (United States)

Kos, Bor; Vásquez, Juan Luis; Miklavčič, Damijan; Hermann, Gregers G G; Gehl, Julie

2016-01-01

Bladder cancer is a cause of considerable morbidity worldwide. Electromotive Drug Administration is a method that combines intravesical chemotherapy with local electric field application. Electroporation has been suggested among other mechanisms as having a possible role in the therapy, so the goal of the present study was to investigate the electric fields present in the bladder wall during the treatment to determine which mechanisms might be involved. Electromotive Drug Administration involves applying intravesical mitomycin C with direct current of 20 mA delivered through a catheter electrode for 30 min. For numerical electric field computation we built a 3-D nonhomogeneous patient specific model based on CT images and used finite element method simulations to determine the electric fields in the whole body. Results indicate that highest electric field in the bladder wall was 37.7 V/m. The mean electric field magnitude in the bladder wall was 3.03 V/m. The mean magnitude of the current density in the bladder wall was 0.61 A/m(2). The present study shows that electroporation is not the mechanism of action in EMDA. A more likely explanation of the mechanism of action is iontophoretic forces increasing the mitomycin C concentration in the bladder wall.

78 FR 26375 - Food and Drug Administration/International Society for Pharmaceutical Engineering Co-Sponsorship...

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2013-05-06

...] Food and Drug Administration/International Society for Pharmaceutical Engineering Co-Sponsorship... Society of Pharmaceutical Engineering (ISPE), is announcing a conference entitled ``Redefining the `C' in CGMP: Creating, Implementing and Sustaining a Culture of Quality'' Pharmaceutical Quality System (ICH...

77 FR 50113 - ASTM International-Food and Drug Administration Workshop on Absorbable Medical Devices: Lessons...

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2012-08-20

... disability, please contact Cindy Garris, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, rm... that the implant must withstand and perform. Moreover, the optimal preclinical/bench testing paradigm...

76 FR 78933 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

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2011-12-20

..., electronic record requirements, and investigator initiated research. Topics for discussion include the...] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical... Clinical Research Associates (SoCRA), is announcing a public workshop. The public workshop on FDA's...

78 FR 9396 - Draft Guidance for Industry and Food and Drug Administration Staff; Civil Money Penalties for...

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2013-02-08

...] Draft Guidance for Industry and Food and Drug Administration Staff; Civil Money Penalties for Tobacco... guidance for industry entitled ``Civil Money Penalties for Tobacco Retailers: Responses to Frequently Asked... civil money penalties for violations of regulations issued under the Federal Food, Drug, and Cosmetic...

78 FR 72900 - Guidance for Industry and Food and Drug Administration Staff; Civil Money Penalties for Tobacco...

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2013-12-04

...] Guidance for Industry and Food and Drug Administration Staff; Civil Money Penalties for Tobacco Retailers... the guidance entitled ``Civil Money Penalties for Tobacco Retailers: Responses to Frequently Asked... issuance of civil money penalties for violations of regulations issued under the Federal Food, Drug, and...

Clinical effectiveness of multiple-drug injection treatment in unruptured ectopic pregnancies: a retrospective study.

Science.gov (United States)

Dai, Quan; Wang, Lu-Lu; Shao, Xiao-Hui; Wang, Si-Ming; Dong, Xiao-Qiu

2012-10-01

To study the effect of local interventional treatment of unruptured ectopic pregnancies with multiple-drug injection guided by color Doppler sonography. In this retrospective analysis, 49 patients with an unruptured ectopic pregnancy were treated with two different local injection methods administered under sonographic guidance. The patients were divided into single-drug (n = 23) and multiple-drug (n = 26) injection groups, and they received a locally administered injection of methotrexate alone or a combination including methotrexate, hemocoagulase, antibiotics, and anti-inflammatory drugs, respectively. Overall, local injection treatment was successful in 44 patients. The 5 patients with failed treatment underwent laparotomy about 1 week after single-drug injection. Serum β-human chorionic gonadotropin (β-hCG ) levels, ectopic pregnancy mass sizes, blood flow at various points after treatment, the incidence of pelvic bleeding, and the time for serum β-hCG levels to return to normal and the mass to resolve were analyzed in the remaining 44 patients. Single-drug treatment was successful in 18 patients; 10 of 23 had low to moderate pelvic bleeding after treatment, and 5 were referred for surgery. All 26 patients were successfully treated by multiple-drug injection. Only 2 patients had a small amount of pelvic bleeding. Differences between groups were statistically significant (P injection under color Doppler guidance is a new, safe, and effective method for treating unruptured ectopic pregnancies. It accelerates the serum β-hCG decline and facilitates mass resolution. This regimen is associated with a very low rate of pelvic bleeding, improves the success rate of conservative treatment, and, therefore, has value as an important clinical application.

Mosaic Structure of a Multiple-Drug-Resistant, Conjugative Plasmid from Campylobacter jejuni

National Research Council Canada - National Science Library

Nirdnoy, Warawadee; Mason, Carl J; Guerry, Patricia

2005-01-01

..., where it apparently integrated into the chromosome and expressed high-level resistance to multiple aminoglycoside antibiotics. This work provides new information about both the nature of drug resistance in C...

75 FR 14448 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

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2010-03-25

... requirements, and investigator initiated research. Topics for discussion include the following: (1) What FDA...] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical... Society of Clinical Research Associates, Inc. (SoCRA) is announcing a public workshop entitled ``FDA...

77 FR 8886 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

Science.gov (United States)

2012-02-15

..., electronic record requirements, and investigator initiated research. Topics for discussion include the...] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical... Research Associates (SoCRA) is announcing a public workshop. The public workshop on FDA's clinical trial...

Microbiological Contamination of Drugs during Their Administration for Anesthesia in the Operating Room.

Science.gov (United States)

Gargiulo, Derryn A; Mitchell, Simon J; Sheridan, Janie; Short, Timothy G; Swift, Simon; Torrie, Jane; Webster, Craig S; Merry, Alan F

2016-04-01

The aseptic techniques of anesthesiologists in the preparation and administration of injected medications have not been extensively investigated, but emerging data demonstrate that inadvertent lapses in aseptic technique may be an important contributor to surgical site and other postoperative infections. A prospective, open, microbiological audit of 303 cases in which anesthesiologists were asked to inject all bolus drugs, except propofol and antibiotics, through a 0.2-µm filter was performed. The authors cultured microorganisms, if present, from the 0.2-µm filter unit and from the residual contents of the syringes used for drawing up or administering drugs. Participating anesthesiologists rated ease of use of the filters after each case. Twenty-three anesthesiologists each anesthetized up to 25 adult patients. The authors isolated microorganisms from filter units in 19 (6.3%) of 300 cases (3 cases were excluded), including Staphylococcus capitis, Staphylococcus warneri, Staphylococcus epidermidis, Staphylococcus haemolyticus, Micrococcus luteus/lylae, Corynebacterium, and Bacillus species. The authors collected used syringes at the end of each case and grew microorganisms from residual drug in 55 of these 2,318 (2.4%) syringes including all the aforementioned microorganisms and also Kocuria kristinae, Staphylococcus aureus, and Staphylococcus hominus. Participants' average rating of ease of use of the filter units was 3.5 out of 10 (0 being very easy and 10 being very difficult). Microorganisms with the potential to cause infection are being injected (presumably inadvertently) into some patients during the administration of intravenous drugs by bolus during anesthesia. The relevance of this finding to postoperative infections warrants further investigation.

76 FR 19998 - Supplemental Funding Under the Food and Drug Administration Pediatric Device Consortia Grant Program

Science.gov (United States)

2011-04-11

...: Linda C. Ulrich, Office of Orphan Products Development, Food and Drug Administration, 10903 New... projects through the development process, including product identification, prototype design, device...

[PHARMACOLOGICAL TREATMENT IN PALLIATIVE CARE. DRUG ADMINISTRATION ROUTE, CONTINUOUS SUBCUTANEOUS INFUSION, ADVERSE SIDE EFFECTS, SYMPTOM MANAGEMENT].

Science.gov (United States)

Dominguez Álvarez, Rocío; Calderón Carrasco, Justo; García Colchero, Francisco; Postigo Mota, Salvador; Alburquerque Medina, Eulalia

2015-01-01

To achieve well-being in patients in Palliative Care is required to know which are the most common symptoms, which are the drugs used for relief, which are the routes of administration of drugs that are suitable, how effective the drugs are and what incompatibilities, interactions and adverse effects occur. The aim of this article is to review the relevant issues in the management of the drugs commonly used by nursing in Palliative Care and presenting recommendations to clinical practice. Management interventions drugs for nurses in Palliative Care recommended by the scientific literature after a search of Scopus, CINAHL, Medline, PubMed, UpToDate and Google Scholar are selected. The oral route is the choice for patients in palliative situation and subcutaneous route when the first is not available. The symptoms, complex, intense and moody, should be systematically reevaluated by the nurse, to predict when a possible decompensation of it needing extra dose of medication. Nurses must be able to recognize the imbalance of well-being and act quickly and effectively, to get relief to some unpleasant situations for the patient as the pain symptoms, dyspnea or delirium. For the proper administration of rescue medication, the nurse should know the methods of symptomatic evaluation, pharmacokinetics and pharmacodynamics of drugs, the time intervals to elapse between different rescues and nccocc rocnnnco t thocm

Factors influencing drug uptake during mass drug administration for control of lymphatic filariasis in rural and urban Tanzania.

Directory of Open Access Journals (Sweden)

William J Kisoka

Full Text Available BACKGROUND: In most countries of Sub-Saharan Africa, control of lymphatic filariasis (LF is based on annual mass drug administration (MDA with a combination of ivermectin and albendazole. Treatment coverages are however often suboptimal for programmes to reach the goal of transmission interruption within reasonable time. The present study aimed to identify predictors and barriers to individual drug uptake during MDA implementation by the National LF Elimination Programme in Tanzania. METHODS: A questionnaire based cross sectional household survey was carried out in two rural and two urban districts in Lindi and Morogoro regions shortly after the 2011 MDA. 3279 adults (≥15 years were interviewed about personal characteristics, socio-economic status, MDA drug uptake among themselves and their children, reasons for taking/not taking drugs, and participation in previous MDA activities for LF control. FINDINGS: The overall drug uptake rate was 55.1% (range of 44.5-75.6% between districts. There was no overall major difference between children (54.8% and adults (55.2% or between females (54.9% and males (55.8%, but the role of these and other predictors varied to some extent between study sites. Major overall predictors of drug uptake among the interviewed adults were increasing age and history of previous drug uptake. Being absent from home during drug distribution was the main reason for not taking the drugs (50.2% followed by clinical contraindications to treatment (10.8%, missing household visits of drug distributors (10.6%, and households not being informed about the distribution (9.0%. CONCLUSION: Drug uptake relied more on easily modifiable provider-related factors than on individual perceptions and practices in the target population. Limited investments in appropriate timing, dissemination of accurate timing information to recipients and motivation of drug distributors to visit all households (repeatedly when residents are absent are likely

76 FR 51040 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

Science.gov (United States)

2011-08-17

... requirements, and investigator initiated research. Topics for discussion include the following: (1) What FDA...] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical... Clinical Research Associates (SoCRA) is announcing a public workshop. The public workshop on FDA's clinical...

Ocular Drug Delivery Barriers—Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases

Science.gov (United States)

Bachu, Rinda Devi; Chowdhury, Pallabitha; Al-Saedi, Zahraa H. F.; Karla, Pradeep K.; Boddu, Sai H. S.

2018-01-01

Ocular drug delivery is challenging due to the presence of anatomical and physiological barriers. These barriers can affect drug entry into the eye following multiple routes of administration (e.g., topical, systemic, and injectable). Topical administration in the form of eye drops is preferred for treating anterior segment diseases, as it is convenient and provides local delivery of drugs. Major concerns with topical delivery include poor drug absorption and low bioavailability. To improve the bioavailability of topically administered drugs, novel drug delivery systems are being investigated. Nanocarrier delivery systems demonstrate enhanced drug permeation and prolonged drug release. This review provides an overview of ocular barriers to anterior segment delivery, along with ways to overcome these barriers using nanocarrier systems. The disposition of nanocarriers following topical administration, their safety, toxicity and clinical trials involving nanocarrier systems are also discussed. PMID:29495528

77 FR 47652 - Second Annual Food and Drug Administration Health Professional Organizations Conference

Science.gov (United States)

2012-08-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001... include an update on the FDA Safety and Innovation Act (Pub. L. 112-144) and an overview of FDA's Network... liaison between FDA Centers and the public on matters that involve medical product safety and also acts as...

Co-treatment with grapefruit juice inhibits while chronic administration activates intestinal P-glycoprotein-mediated drug efflux.

Science.gov (United States)

Panchagnula, R; Bansal, T; Varma, M V S; Kaul, C L

2005-12-01

P-Glycoprotein (P-gp) mediated efflux is recognized as a significant biochemical barrier affecting oral absorption for a number of drugs. Various conflicting reports have been published regarding the effects of grapefruit juice (GFJ) on P-gp-mediated drug efflux, in which GFJ has been shown both to inhibit and activate it. Hence, the present study adopted a two-way approach, involving both co-treatment and chronic administration. Bi-directional transport of paclitaxel (PCL) was carried out in the absence and presence of GFJ extract, in rat everted ileum sac. Further, the effect of chronic administration of GFJ to rats was characterized by permeability studies with indinavir (INDI). Co-treatment of GFJ extract at 100% concentration reduced the asymmetric transport of PCL (efflux ratio = 20.8) by increasing absorptive (A --> B) transport by 921% and reducing secretory (B --> A) transport by 41%. Further, GFJ showed a concentration dependent effect on PCL permeability. Imipramine, a passive permeability marker with absorptive permeability of 15.33 +/- 4.26 x 10(-6) cm/s showed no asymmetric transport and also no significant (P extract inhibited P-gp-mediated efflux in co-treatment, whereas chronic administration led to increased levels of P-gp expression, thus having a profound effect on intestinal absorption and GFJ-drug interactions in vivo.

Quantification of drug-loaded magnetic nanoparticles in rabbit liver and tumor after in vivo administration

Energy Technology Data Exchange (ETDEWEB)

Tietze, Rainer; Jurgons, Roland; Lyer, Stefan; Schreiber, Eveline [Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-University Erlangen-Nuernberg, Waldstr. 1, 91054 Erlangen (Germany); Wiekhorst, Frank; Eberbeck, Dietmar; Richter, Heike; Steinhoff, Uwe; Trahms, Lutz [Physikalisch-Technische Bundesanstalt, Berlin (Germany); Alexiou, Christoph [Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-University Erlangen-Nuernberg, Waldstr. 1, 91054 Erlangen (Germany)], E-mail: C.Alexiou@web.de

2009-05-15

Magnetic nanoparticles have been investigated for biomedical applications for more than 30 years. The development of biocompatible nanosized drug delivery systems for specific targeting of therapeutics is imminent in medical research, especially for treating cancer and vascular diseases. We used drug-labeled magnetic iron oxide nanoparticles, which were attracted to an experimental tumor in rabbits with an external magnetic field (magnetic drug targeting, MDT). Aim of this study was to detect and quantify the biodistribution of the magnetic nanoparticles by magnetorelaxometry. The study shows higher amount of nanoparticles in the tumor after intraarterial application and MDT compared to intravenous administration.

Central neurotoxicity of immunomodulatory drugs in multiple myeloma

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Urmeel H. Patel

2015-03-01

Full Text Available Immunomodulatory drugs (IMiDs currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient, lenalidomide (4 patients, and pomalidomide (1 patient was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy.

Central neurotoxicity of immunomodulatory drugs in multiple myeloma.

Science.gov (United States)

Patel, Urmeel H; Mir, Muhammad A; Sivik, Jeffrey K; Raheja, Divisha; Pandey, Manoj K; Talamo, Giampaolo

2015-02-24

Immunomodulatory drugs (IMiDs) currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient), lenalidomide (4 patients), and pomalidomide (1 patient) was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy.

Recent advances in multiple myeloma: a Korean perspective

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Hong, Junshik; Lee, Jae Hoon

2016-01-01

Epidemiologically, multiple myeloma (MM) is a malignant disorder of plasma cells with a higher incidence among Western populations than among Asians. However, there is growing evidence of a recent increase in the age-standardized incidence rate (ASR) of MM in Asian countries, particularly Korea. Application of novel agents has resulted in significant improvement of treatment outcomes, and the advances are ongoing with the recent introduction and U.S. Food and Drug Administration?s approval of...

Polyethyleneimine-modified iron oxide nanoparticles for brain tumor drug delivery using magnetic targeting and intra-carotid administration.

Science.gov (United States)

Chertok, Beata; David, Allan E; Yang, Victor C

2010-08-01

This study aimed to examine the applicability of polyethyleneimine (PEI)-modified magnetic nanoparticles (GPEI) as a potential vascular drug/gene carrier to brain tumors. In vitro, GPEI exhibited high cell association and low cell toxicity--properties which are highly desirable for intracellular drug/gene delivery. In addition, a high saturation magnetization of 93 emu/g Fe was expected to facilitate magnetic targeting of GPEI to brain tumor lesions. However, following intravenous administration, GPEI could not be magnetically accumulated in tumors of rats harboring orthotopic 9L-gliosarcomas due to its poor pharmacokinetic properties, reflected by a negligibly low plasma AUC of 12 +/- 3 microg Fe/ml min. To improve "passive" GPEI presentation to brain tumor vasculature for subsequent "active" magnetic capture, we examined the intra-carotid route as an alternative for nanoparticle administration. Intra-carotid administration in conjunction with magnetic targeting resulted in 30-fold (p=0.002) increase in tumor entrapment of GPEI compared to that seen with intravenous administration. In addition, magnetic accumulation of cationic GPEI (zeta-potential = + 37.2 mV) in tumor lesions was 5.2-fold higher (p=0.004) than that achieved with slightly anionic G100 (zeta-potential= -12 mV) following intra-carotid administration, while no significant accumulation difference was detected between the two types of nanoparticles in the contra-lateral brain (p=0.187). These promising results warrant further investigation of GPEI as a potential cell-permeable, magnetically-responsive platform for brain tumor delivery of drugs and genes. 2010 Elsevier Ltd. All rights reserved.

Withanolide D Exhibits Similar Cytostatic Effect in Drug-Resistant and Drug-Sensitive Multiple Myeloma Cells

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Mark E. Issa

2017-09-01

Full Text Available In spite of recent therapeutic advances, multiple myeloma (MM remains a malignancy with very low curability. This has been partly attributed to the existence of a drug-resistant subpopulation known as cancer stem cells (CSCs. MM-CSCs are equipped with the necessary tools that render them highly resistant to virtually all conventional therapies. In this study, the growth inhibitory effects of withanolide D (WND, a steroidal lactone isolated from Withania somnifera, on drug-sensitive tumoral plasma cells and drug-resistant MM cells have been investigated. In MTT/XTT assays, WND exhibited similar cytostatic effects between drug-resistant and drug-sensitive cell lines in the nM range. WND also induced cell death and apoptosis in MM-CSCs and RPMI 8226 cells, as examined by the calcein/ethidium homodimer and annexin V/propidium iodide stainings, respectively. To determine whether P-glycoprotein (P-gp efflux affected the cytostatic activity of WND, P-gp was inhibited with verapamil and results indicated that the WND cytostatic effect in MM-CSCs was independent of P-gp efflux. Furthermore, WND did not increase the accumulation of the fluorescent P-gp substrate rhodamine 123 in MM-CSCs, suggesting that WND may not inhibit P-gp at the tested relevant doses. Therefore, the WND-induced cytostatic effect may be independent of P-gp efflux. These findings warrant further investigation of WND in MM-CSC animal models.

Pharmacoeconomic analysis of the use of first- and second-line drugs in the treatment of multiple sclerosis

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V. R. Mkrtchyan

2015-01-01

Full Text Available Objective: to make a pharmacoeconomic comparison of the administration of first- and second-line drugs in the treatment of multiple sclerosis through cost, cost-effectiveness, and budget impact analyses using the 2015 state prices.Material and methods. A pharmacoeconomic analysis was carried out on the basis of the data available in the literature on trials of the effects of the drugs on the rates of exacerbations and disability. On calculating, the authors took into account the current standards for the out- and inpatient management of patients with this nosological entity in accordance with the compulsory health insurance (CHI program; prices for state drug purchases in March 2015; prices for medical services in compliance with the CHI standards in Moscow in 2015; the average sizes of minimum wage, salary, and disability grants with consideration for a discount rate of 3%. The cost-effectiveness and budget impact analyses were performed for intramuscular interferon (INF-β1a (avonex, 30 μg, subcutaneous INF-β1a (rebif, 44 μg, subcutaneous INF-β1b (ronbetal, 8,000,000 IU, subcutaneous INF-β1b (betaferon, 9,600,000 IU, subcutaneous glatiramer acetate (copaxone, 20 mg, intravenous natalizumab (tyzabri, 300 mg, and oral fingolimod (gilenya, 0.5 mg.Results and discussion. The second-line drug tyzabri outperforms the first-line agents for cost-effectiveness. The first-line drugs betaferon and copaxone is slightly exceeded in this indicator by tyzabri; the other both first- and second-line agents compared are all the more inferior in this indicator. The budget impact analysis has shown that the cost of the second-line drugs was higher than that of the first-line ones.

77 FR 39498 - Guidances for Industry and Food and Drug Administration Staff: Computer-Assisted Detection...

Science.gov (United States)

2012-07-03

...] Guidances for Industry and Food and Drug Administration Staff: Computer-Assisted Detection Devices Applied... Clinical Performance Assessment: Considerations for Computer-Assisted Detection Devices Applied to... guidance, entitled ``Computer-Assisted Detection Devices Applied to Radiology Images and Radiology Device...

A tale of two citizens: a State Attorney General and a hematologist facilitate translation of research into US Food and Drug Administration actions--a SONAR report.

Science.gov (United States)

Chen, Brian; Restaino, John; Norris, LeAnn; Xirasagar, Sudha; Qureshi, Zaina P; McKoy, June M; Lopez, Isaac S; Trenery, Alyssa; Murday, Alanna; Kahn, Adam; Mattison, Donald R; Ray, Paul; Sartor, Oliver; Bennett, Charles L

2012-11-01

Pharmaceutical safety is a public health issue. In 2005, the Connecticut Attorney General (AG) raised concerns over adverse drug reactions in off-label settings, noting that thalidomide was approved to treat a rare illness, but more than 90% of its use was off label. A hematologist had reported thalidomide with doxorubicin or dexamethasone was associated with venous thromboembolism (VTE) rates of 25%. We review US Food and Drug Administration (FDA) and manufacturer responses to a citizen petition filed to address these thalidomide safety issues. Case study. The AG petitioned the FDA requesting thalidomide-related safety actions. Coincidentally, the manufacturer submitted a supplemental New Drug Approval (sNDA), requesting approval to treat multiple myeloma with thalidomide-dexamethasone. FDA safety officers reviewed the petition and the literature and noted that VTE risks with thalidomide were not appropriately addressed in the existing package insert. In the sNDA application, the manufacturer reported thalidomide-associated toxicities for multiple myeloma were primarily somnolence and neurotoxicity, and a proposed package insert did not focus on VTE risks. In October, the FDA informed the Oncology Drug Division that VTE risks with thalidomide were poorly addressed in the existing label. After reviewing this memorandum, an Oncology Drug Division reviewer informed the manufacturer that approval of the sNDA would be delayed until several thalidomide-associated VTE safety actions, including revisions of the package insert, were implemented. The manufacturer and FDA agreed on these actions, and the sNDA was approved. New approaches addressing off-label safety are needed. The conditions that facilitated the successful response to this citizen petition are uncommon.

THE EFFECT OF DIFFERENT TB DRUGS AND ANTIMICROBIAL AGENTS ON THE EFFICIENCY OF TREATMENT OF TUBERCULOSIS PATIENTS WITH MULTIPLE DRUG RESISTANCE

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I. A. Vasilyeva

2017-01-01

Full Text Available Objective of the study: to study the effect of specific TB drugs and antimicrobial agents constituting chemotherapy regimens on the efficiency of treatment of tuberculosis patients with various patterns of multiple drug resistance.Subjects and Methods. 412 pulmonary tuberculosis patients with bacillary excretion and various patterns of multiple drug resistance were enrolled into the study (117 patients with MDR TB (non pre-XDR and non-XDR; 120 patients with pre-XDR TB and 175 with XDR TB. Patients in the subgroups were compatible regarding sex and age. The patients were prescribed regimens including 5-6 drugs in accordance with their drug resistance pattern. The time of sputum conversion (by culture versus the year of treatment was selected as a surrogate endpoint. The effect of specific TB drugs and antimicrobial agents on treatment efficiency was assessed through calculation of odds ratio (OR of achieving a surrogate endpoint in the patients receiving and not receiving a certain drug.Results. In the subgroup of pre-XDR TB, the following drugs demonstrated the valid increase of odds of sputum conversion: ethambutol (OR 11.8, pyrazinamide (OR 10.2, moxifloxacin (OR 7.8, capreomicin (OR 4.41. Sputum conversion was achieved in all 11 patients treated with bedaquiline.In the subgroup of XDR TB, the following drugs provided a positive effect on the achievement of sputum conversion: bedaquiline (OR 9.62, linezolid (OR 8.15, cycloserine (OR 7.88, pyrazinamide (OR 7.29, moxifloxacin (OR 7.08, and ethambutol (OR 6.69. Ofloxacin demonstrated a confident negative effect on achieving sputum conversion (95% CI 0.06-0.32. 

75 FR 4407 - Science Board to the Food and Drug Administration; Notice of Meeting

Science.gov (United States)

2010-01-27

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001... subcommittee reviewing research at the Center for Food Safety and Applied Nutrition. The Science Board will... person on or before Monday, February 15, 2010. Oral presentations from the public will be scheduled...

78 FR 13070 - Guidance for Clinical Investigators, Industry, and Food and Drug Administration Staff: Financial...

Science.gov (United States)

2013-02-26

... marketing applications, (2) what is meant by ``due diligence'' in obtaining financial disclosures from...: Financial Disclosure by Clinical Investigators; Availability AGENCY: Food and Drug Administration, HHS... guidance entitled ``Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by...

[Construction of multiple drug release system based on components of traditional Chinese medicine].

Science.gov (United States)

Liu, Dan; Jia, Xiaobin; Yu, Danhong; Zhang, Zhenhai; Sun, E

2012-08-01

With the development of the modernization drive of traditional Chinese medicine (TCM) preparations, new-type TCM dosage forms research have become a hot spot in the field. Because of complexity of TCM components as well as uncertainty of material base, there is still not a scientific system for modern TCM dosage forms so far. Modern TCM preparations inevitably take the nature of the multi-component and the general function characteristics of multi-link and multi-target into account. The author suggests building a multiple drug release system for TCM using diverse preparation techniques and drug release methods at levels on the basis the nature and function characteristics of TCM components. This essay expounds elaborates the ideas to build the multiple traditional Chinese medicine release system, theoretical basis, preparation techniques and assessment system, current problems and solutions, in order to build a multiple TCM release system with a view of enhancing the bioavailability of TCM components and provide a new form for TCM preparations.

Antibacterial activity of combined medicinal plants extract against multiple drug resistant strains

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Rafiqul Islam

2015-06-01

Full Text Available Objective: To find out the combined antibacterial efficacy of Aegle marmelos, Aphanamixis polystachya, Cuscuta reflexa and Aesclynomene indica against bacterial pathogens. Methods: Antibacterial potency of combined plant extracts has been tested against Bacillus subtilis IFO 3026, Sarcina lutea IFO 3232, Xanthomonas campestris IAM 1671, Escherichia coli IFO 3007, Klebsiella pneumoniae ATTC 10031, Proteus vulgaris MTCC 321 and Pseudomonas denitrificans KACC 32026 by disc diffusion assay. Commercially available standard antibiotic discs were also used to find out antibiotic resistance pattern of test organisms. Results: Among the test organisms, Escherichia coli, Proteus vulgaris, Klebsiella pneumoniae and Proteus denitrificans showed resistance against multiple commercially available antibiotics. On the other hand, these multiple drug resistant organisms showed susceptibility against combined plant extracts. Conclusions: These combined plants extracts showed synergistic antibacterial activity and could lead to new antibacterial drug designing.

Comparative pharmacokinetics of oxytetracycline in blunt-snout bream (Megalobrama amblycephala) with single and multiple-dose oral administration.

Science.gov (United States)

Li, Ru-Qin; Ren, Yu-Wei; Li, Jing; Huang, Can; Shao, Jun-Hui; Chen, Xiao-Xuan; Wu, Zhi-Xin

2015-06-01

Research into the pharmacokinetics and residue elimination of oxytetracycline (OTC) is important both to determine the optimal dosage regimens and to establish a safe withdrawal time in fish. A depletion study is presented here for OTC in Megalobrama amblycephala with a single-dose (100 mg/kg) and multiple-dose (100 mg/kg for five consecutive days) oral administration. The study was conducted at 25 °C. As a result, a one-compartment model was developed. For the single dose, the absorption half-life was 5.79, 9.40, 6.96, and 8.06 h in the plasma, liver, kidney, and muscle, respectively. However, the absorption half-life was 3.62, 7.33, 4.59, and 6.02 h with multiple-dose oral administration. The elimination half-time in the plasma, liver, kidney, and muscle was 58.63, 126.43, 65.1, and 58.85 h when M. amblycephala was treated with a single dose. However, the elimination half-time changed to 91.75, 214.87, 126.22, and 135.84 h with multiple-dose oral administration.

Administrative support of novice science teachers: A multiple case study

Science.gov (United States)

Iacuone, Leann

Novice science teachers leave the confines of colleges and universities to embark on a new adventure in education where they aim to influence young minds, make a difference in the world, and share their love for their content. They have learned their pedagogical skills with the support and assistance of fellow classmates, a supporting professor, and a cooperating teacher. These teachers enter their new place of employment and are met with many unexpected challenges, such as a lack of resources, no one to ask questions of, and a busy staff with already established relationships, causing them to feel an overall lack of support and resulting in many new teachers rethinking their career choice and leaving the field of education within 5 years of entering. This multiple-case study investigated the administrative support 4 novice science teachers received during an academic year and the novice teachers' perceptions of the support they received to answer the following research question: How do novice science teachers who have consistent interactions with administrators develop during their first year? To answer this question, semistructured interviews, reflection journals, observations, resumes, long-range plans, and student discipline referrals were collected. The findings from this study show novice science teachers who had incidents occur in the classroom requiring administrative assistance and guidance felt more confident in enforcing their classroom management policies and procedures as the year progressed to change student behavior. The novice science teachers perceived administrators who provided resources including technology, office supplies, science supplies, and the guidance of a mentor as supportive. Novice science teachers who engaged in dialogue after administrative observations, were provided the opportunity to attend professional development outside the district, and had a mentor who taught the same discipline made more changes to their instructional

Program Administrator's Handbook. Strategies for Preventing Alcohol and Other Drug Problems. The College Series.

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CSR, Inc., Washington, DC.

This handbook is for administrators of programs in higher education settings which deal with alcohol and other drug (AOD) related problems. Chapter 1, "Defining the Problem, Issues, and Trends" examines the problem from various perspectives and presents the latest statistics on the extent of AOD use on campuses, specific problems affecting…

A multiple biomarker assay for quality assessment of botanical drugs using a versatile microfluidic chip.

Science.gov (United States)

Li, Zhen-Hao; Ai, Ni; Yu, Lawrence X; Qian, Zhong-Zhi; Cheng, Yi-Yu

2017-09-25

Quality control is critical for ensuring the safety and effectiveness of drugs. Current quality control method for botanical drugs is mainly based on chemical testing. However, chemical testing alone may not be sufficient as it may not capture all constituents of botanical drugs. Therefore, it is necessary to establish a bioassay correlating with the drug's known mechanism of action to ensure its potency and activity. Herein we developed a multiple biomarker assay to assess the quality of botanicals using microfluidics, where enzyme inhibition was employed to indicate the drug's activity and thereby evaluate biological consistency. This approach was exemplified on QiShenYiQi Pills using thrombin and angiotensin converting enzyme as "quality biomarkers". Our results demonstrated that there existed variations in potency across different batches of the intermediates and preparations. Compared with chromatographic fingerprinting, the bioassay provided better discrimination ability for some abnormal samples. Moreover, the chip could function as "affinity chromatography" to identify bioactive phytochemicals bound to the enzymes. This work proposed a multiple-biomarker strategy for quality assessment of botanical drugs, while demonstrating for the first time the feasibility of microfluidics in this field.

Drug Safety: Managing Multiple Drugs

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... This series is produced by Consumers Union and Consumer Reports Best Buy Drugs , a public information project sup- ported by grants from the Engelberg Foundation and the National Library of Medicine of ... Consumer and Prescriber Education Grant Program which is funded ...

77 FR 49449 - Food and Drug Administration Clinical Trial Requirements, Compliance, and Good Clinical Practice...

Science.gov (United States)

2012-08-16

... investigator initiated research. Topics for discussion include the following: (1) What FDA Expects in a...] Food and Drug Administration Clinical Trial Requirements, Compliance, and Good Clinical Practice...-sponsorship with the Society of Clinical Research Associates (SoCRA) is announcing a public workshop. The...

76 FR 38666 - Food and Drug Administration (FDA) and Marine Environmental Sciences Consortium/Dauphin Island...

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2011-07-01

...-mail: [email protected] . Grants Management Contact Gladys Melendez-Bohler, Office of..., MD 20857, Tele.: 301-827-7175; e-mail: Gladys[email protected] . For more information on...: Gladys Melendez-Bohler, Office of Acquisition and Grant Services (OAGS), Food and Drug Administration...

Spotlight on ixazomib: potential in the treatment of multiple myeloma

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Muz B

2016-01-01

Full Text Available Barbara Muz,1 Rachel Nicole Ghazarian,1,2 Monica Ou,1,3 Micah John Luderer,1 Hubert Daniel Kusdono,1,2 Abdel Kareem Azab1 1Department of Radiation Oncology, Cancer Biology Division, Washington University in St Louis School of Medicine, 2Department of Pharmaceutical and Administrative Sciences, St Louis College of Pharmacy, 3Department of Biology, St Louis University, St Louis, MO, USA Abstract: Despite the significant therapeutic advances achieved with proteasome inhibitors (PIs such as bortezomib and carfilzomib in prolonging the survival of patients with multiple myeloma, the development of drug resistance, peripheral neuropathy, and pharmacokinetic limitations continue to pose major challenges when using these compounds. Ixazomib is a second-generation PI with improved activity over other PIs. Unlike bortezomib and carfilzomib, which are administered by injection, ixazomib is the first oral PI approved by US Food and Drug Administration. This review discusses the biochemical properties, mechanisms of action, preclinical efficacy, and clinical trial results leading to the US Food and Drug Administration approval of ixazomib. Keywords: proteasome inhibitor, oral administration, biological mechanism, clinical trials

[Diffuse large B-cell lymphoma complicated with drug-induced vasculitis during administration of pegfilgrastim].

Science.gov (United States)

Ito, Yuta; Noda, Kentaro; Aiba, Keisuke; Yano, Shingo; Fujii, Tsunehiro

A 59-year-old female with diffuse large B-cell lymphoma was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) regimen. In addition, we administered pegfilgrastim for treating chemotherapy-induced febrile neutropenia. She complained of fever and neck and chest pain a few days after pegfilgrastim administration during the third and fourth courses of R-CHOP. Radiological imaging revealed an inflammation of large vessels, which led to the diagnosis of drug-associated vasculitis. We confirmed that vasculitis observed in this case was caused by pegfilgrastim administration because similar symptoms appeared with both injections of pegfilgrastim.

Comparison of self-administration behavior and responsiveness to drug-paired cues in rats running an alley for intravenous heroin and cocaine.

Science.gov (United States)

Su, Zu-In; Wenzel, Jennifer; Baird, Rebeccah; Ettenberg, Aaron

2011-04-01

Evidence suggests that responsiveness to a drug-paired cue is predicted by the reinforcing magnitude of the drug during prior self-administration. It remains unclear, however, if this principle holds true when comparisons are made across drug reinforcers. The current study was therefore devised to test the hypothesis that differences in the animals' responsiveness to a cocaine- or heroin-paired cue presented during extinction would reflect differences in the patterns of prior cocaine and heroin runway self-administration. Rats ran a straight alley for single intravenous injections of either heroin (0.1 mg/kg/inj) or cocaine (1.0 mg/kg/inj) each paired with a distinct olfactory cue. Animals experienced 15 trials with each drug reinforcer in a counterbalanced manner. Start latencies, run times, and retreat behaviors (a form of approach-avoidance conflict) provided behavioral indices of the subjects' motivation to seek the reinforcer on each trial. Responsiveness to each drug-paired cue was assessed after 7, 14, or 21 days of non-reinforced extinction trials. Other animals underwent conditioned place preference (CPP) testing to ensure that the two drug reinforcers were capable of producing drug-cue associations. While both drugs produced comparable CPPs, heroin served as a stronger incentive stimulus in the runway as evidenced by faster start and run times and fewer retreats. In contrast, cocaine- but not heroin-paired cues produced increases in drug-seeking behavior during subsequent extinction trials. The subjects' responsiveness to drug-paired cues during extinction was not predicted by differences in the motivation to seek heroin versus cocaine during prior drug self-administration.

EMUDRA: Ensemble of Multiple Drug Repositioning Approaches to Improve Prediction Accuracy.

Science.gov (United States)

Zhou, Xianxiao; Wang, Minghui; Katsyv, Igor; Irie, Hanna; Zhang, Bin

2018-04-24

Availability of large-scale genomic, epigenetic and proteomic data in complex diseases makes it possible to objectively and comprehensively identify therapeutic targets that can lead to new therapies. The Connectivity Map has been widely used to explore novel indications of existing drugs. However, the prediction accuracy of the existing methods, such as Kolmogorov-Smirnov statistic remains low. Here we present a novel high-performance drug repositioning approach that improves over the state-of-the-art methods. We first designed an expression weighted cosine method (EWCos) to minimize the influence of the uninformative expression changes and then developed an ensemble approach termed EMUDRA (Ensemble of Multiple Drug Repositioning Approaches) to integrate EWCos and three existing state-of-the-art methods. EMUDRA significantly outperformed individual drug repositioning methods when applied to simulated and independent evaluation datasets. We predicted using EMUDRA and experimentally validated an antibiotic rifabutin as an inhibitor of cell growth in triple negative breast cancer. EMUDRA can identify drugs that more effectively target disease gene signatures and will thus be a useful tool for identifying novel therapies for complex diseases and predicting new indications for existing drugs. The EMUDRA R package is available at doi:10.7303/syn11510888. bin.zhang@mssm.edu or zhangb@hotmail.com. Supplementary data are available at Bioinformatics online.

Dodecyltriphenylphosphonium inhibits multiple drug resistance in the yeast Saccharomyces cerevisiae.

Science.gov (United States)

Knorre, Dmitry A; Markova, Olga V; Smirnova, Ekaterina A; Karavaeva, Iuliia E; Sokolov, Svyatoslav S; Severin, Fedor F

2014-08-08

Multiple drug resistance pumps are potential drug targets. Here we asked whether the lipophilic cation dodecyltriphenylphosphonium (C12TPP) can interfere with their functioning. First, we found that suppression of ABC transporter gene PDR5 increases the toxicity of C12TPP in yeast. Second, C12TPP appeared to prevent the efflux of rhodamine 6G - a fluorescent substrate of Pdr5p. Moreover, C12TPP increased the cytostatic effects of some other known Pdr5p substrates. The chemical nature of C12TPP suggests that after Pdr5p-driven extrusion the molecules return to the plasma membrane and then into the cytosol, thus effectively competing with other substrates of the pump. Copyright © 2014 Elsevier Inc. All rights reserved.

Emerging drugs for primary progressive multiple sclerosis.

Science.gov (United States)

Narayan, Ram Narendra; Forsthuber, Thomas; Stüve, Olaf

2018-04-24

The identification of effective therapies for progressive forms of multiple sclerosis (MS) has remains a priority and challenge for the global MS community. Despite a few proposed mechanisms, a more complete understanding of the mechanisms involved in the pathogenesis of these MS phenotypes, animal models that incorporate these pathogenic characteristics, novel trial designs, drug repurposing strategies, and new models of collaboration between clinical and basic science personnel may be required in identifying effective therapies. Areas covered: Here, we review the current knowledge on putative pathogenic mechanisms in primary progressive MS (PPMS). Also, the rationale and outcomes of key phase II or III trial initiatives in PPMS are summarized. Future perspectives are outlined. Expert opinion: The recent approval of ocrelizumab is a major milestone forward in the therapy of PPMS. One reason for success of this drug is appropriate patient selection. The ultimate goal in PPMS therapy should be the reversal of disability, and the arrest of disease progression. Our current understanding of PPMS suggests that a combination of immune-modulatory, myelin-restorative, and neuro-regenerative therapies particularly early in the disease course would be a reasonable strategy. Finally, selection of appropriate patients, selection of appropriate outcomes and monitoring therapy is again crucial for success of therapeutic strategies.

78 FR 59038 - Mobile Medical Applications; Guidance for Industry and Food and Drug Administration Staff...

Science.gov (United States)

2013-09-25

... FDA intends to apply its regulatory oversight to only those mobile apps that are medical devices and...] Mobile Medical Applications; Guidance for Industry and Food and Drug Administration Staff; Availability...) is announcing the availability of the guidance entitled ``Mobile Medical Applications.'' The FDA is...

Molecular pharmacodynamics of new oral drugs used in the treatment of multiple sclerosis

Directory of Open Access Journals (Sweden)

di Nuzzo L

2014-05-01

Full Text Available Luigi di Nuzzo,1 Rosamaria Orlando,2 Carla Nasca,1 Ferdinando Nicoletti1,31Department of Physiology and Pharmacology, Sapienza University of Rome, 2IRCCS Associazione Oasi Maria S.S., Institute for Research on Mental Retardation and Brain Aging, Troina, Enna, 3IRCCS Neuromed, Pozzilli, ItalyAbstract: New oral drugs have considerably enriched the therapeutic armamentarium for the treatment of multiple sclerosis. This review focuses on the molecular pharmacodynamics of fingolimod, dimethyl fumarate (BG-12, laquinimod, and teriflunomide. We specifically comment on the action of these drugs at three levels: 1 the regulation of the immune system; 2 the permeability of the blood–brain barrier; and 3 the central nervous system. Fingolimod phosphate (the active metabolite of fingolimod has a unique mechanism of action and represents the first ligand of G-protein-coupled receptors (sphingosine-1-phosphate receptors active in the treatment of multiple sclerosis. Dimethyl fumarate activates the nuclear factor (erythroid-derived 2-related factor 2 pathway of cell defense as a result of an initial depletion of reduced glutathione. We discuss how this mechanism lies on the border between cell protection and toxicity. Laquinimod has multiple (but less defined mechanisms of action, which make the drug slightly more effective on disability progression than on annualized relapse rate in clinical studies. Teriflunomide acts as a specific inhibitor of the de novo pyrimidine biosynthesis. We also discuss new unexpected mechanisms of these drugs, such as the induction of brain-derived neurotrophic factor by fingolimod and the possibility that laquinimod and teriflunomide regulate the kynurenine pathway of tryptophan metabolism.Keywords: demyelinating diseases, pharmacotherapy, fingolimod, dimethyl fumarate, laquinimod, teriflunomide

Regulatory aspects of teratology: role of the Food and Drug Administration

International Nuclear Information System (INIS)

Kelsey, F.O.

1982-01-01

The Food and Drug Administration is a scientific regulatory agency whose consumer protection activities cover a wide range of products including foods and additives, and pesticide residues on foods; drugs; cosmetics; medical devices; and radiation-emitting electronic products. Amongst its concerns is the possible teratogen effects of regulated products to which the pregnant woman is exposed. The policies and programs of the agency directed toward reducing such risks to the unborn are reviewed. These measures include guidelines for animal reproduction studies and for clinical trials involving women to childbearing potential; labeling of products to disclose known or possible harm to the fetus or embryo; surveillance procedures designed to detect previously unsuspected adverse effects of marketed products; research activities designed to develop better understanding of developmental toxicology and improved techniques for detecting embryocidal and embryotoxic effects; and educational efforts directed both to professionals and the public regarding hazards to the unborn of agency-regulated products

Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study.

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Fleming, J O; Isaak, A; Lee, J E; Luzzio, C C; Carrithers, M D; Cook, T D; Field, A S; Boland, J; Fabry, Z

2011-06-01

Probiotic treatment strategy based on the hygiene hypothesis, such as administration of ova from the non-pathogenic helminth, Trichuris suis, (TSO) has proven safe and effective in autoimmune inflammatory bowel disease. To study the safety and effects of TSO in a second autoimmune disease, multiple sclerosis (MS), we conducted the phase 1 Helminth-induced Immunomodulatory Therapy (HINT 1) study. Five subjects with newly diagnosed, treatment-naive relapsing-remitting multiple sclerosis (RRMS) were given 2500 TSO orally every 2 weeks for 3 months in a baseline versus treatment control exploratory trial. The mean number of new gadolinium-enhancing magnetic resonance imaging (MRI) lesions (n-Gd+) fell from 6.6 at baseline to 2.0 at the end of TSO administration, and 2 months after TSO was discontinued, the mean number of n-Gd+ rose to 5.8. No significant adverse effects were observed. In preliminary immunological investigations, increases in the serum level of the cytokines IL-4 and IL-10 were noted in four of the five subjects. TSO was well tolerated in the first human study of this novel probiotic in RRMS, and favorable trends were observed in exploratory MRI and immunological assessments. Further investigations will be required to fully explore the safety, effects, and mechanism of action of this immunomodulatory treatment.

Cyclophosphamide administration routine in autoimmune rheumatic diseases: a review

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Kaian Amorim Teles

Full Text Available Abstract Cyclophosphamide is an alkylating agent widely used for the treatment of malignant neoplasia and which can be used in the treatment of multiple rheumatic diseases. Medication administration errors may lead to its reduced efficacy or increased drug toxicity. Many errors occur in the administration of injectable drugs. The present study aimed at structuring a routine for cyclophosphamide use, as well as creating a document with pharmacotherapeutic guidelines for the patient. The routine is schematized in three phases: pre-chemotherapy, administration of cyclophosphamide, and post-chemotherapy, taking into account the drugs to be administered before and after cyclophosphamide in order to prevent adverse effects, including nausea and hemorrhagic cystitis. Adverse reactions can alter laboratory tests; thus, this routine included clinical management for changes in white blood cells, platelets, neutrophils, and sodium, including cyclophosphamide dose adjustment in the case of kidney disease. Cyclophosphamide is responsible for other rare - but serious - side effects, for instance, hepatotoxicity, severe hyponatremia and heart failure. Other adverse reactions include hair loss, amenorrhea and menopause. In this routine, we also entered guidelines to post-chemotherapy patients. The compatibility of injectable drugs with the vehicle used has been described, as well as stability and infusion times. The routine aimed at the rational use of cyclophosphamide, with prevention of adverse events and relapse episodes, factors that may burden the health care system.

Two cases of corneal perforation after oral administration of nonsteroidal anti-inflammatory drugs: oral NSAID-induced corneal damage.

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Masuda, Ikuya; Matsuo, Toshihiko; Okamoto, Kazuo; Matsushita, Kyoko; Ohtsuki, Hiroshi

2010-01-01

To report 2 cases of corneal perforation associated with the use of oral nonsteroidal anti-inflammatory drugs (NSAIDs). In a 62-year-old woman and a 79-year-old woman, corneal perforation occurred after 7 days and 5 months of oral NSAIDs administration, respectively. After NSAIDs were discontinued, the cornea epithelialized and the anterior chamber formed within 14 and 10 days, respectively. It is well known that topical NSAIDs cause corneal perforation. Observations in the present cases suggest that the oral administration of NSAIDs may also cause corneal damage, and hence, medical professionals should consider the risk of damage to the cornea when administering these drugs orally.

A Tale of Two Citizens: A State Attorney General and a Hematologist Facilitate Translation of Research Into US Food and Drug Administration Actions—A SONAR Report

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Chen, Brian; Restaino, John; Norris, LeAnn; Xirasagar, Sudha; Qureshi, Zaina P.; McKoy, June M.; Lopez, Isaac S.; Trenery, Alyssa; Murday, Alanna; Kahn, Adam; Mattison, Donald R.; Ray, Paul; Sartor, Oliver; Bennett, Charles L.

2012-01-01

Purpose: Pharmaceutical safety is a public health issue. In 2005, the Connecticut Attorney General (AG) raised concerns over adverse drug reactions in off-label settings, noting that thalidomide was approved to treat a rare illness, but more than 90% of its use was off label. A hematologist had reported thalidomide with doxorubicin or dexamethasone was associated with venous thromboembolism (VTE) rates of 25%. We review US Food and Drug Administration (FDA) and manufacturer responses to a citizen petition filed to address these thalidomide safety issues. Methods: Case study. Results: The AG petitioned the FDA requesting thalidomide-related safety actions. Coincidentally, the manufacturer submitted a supplemental New Drug Approval (sNDA), requesting approval to treat multiple myeloma with thalidomide-dexamethasone. FDA safety officers reviewed the petition and the literature and noted that VTE risks with thalidomide were not appropriately addressed in the existing package insert. In the sNDA application, the manufacturer reported thalidomide-associated toxicities for multiple myeloma were primarily somnolence and neurotoxicity, and a proposed package insert did not focus on VTE risks. In October, the FDA informed the Oncology Drug Division that VTE risks with thalidomide were poorly addressed in the existing label. After reviewing this memorandum, an Oncology Drug Division reviewer informed the manufacturer that approval of the sNDA would be delayed until several thalidomide-associated VTE safety actions, including revisions of the package insert, were implemented. The manufacturer and FDA agreed on these actions, and the sNDA was approved. Conclusion: New approaches addressing off-label safety are needed. The conditions that facilitated the successful response to this citizen petition are uncommon. PMID:23598851

Effect of administration method, animal weight and age on the intranasal delivery of drugs to the brain.

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Krishnan, Jishnu K S; Arun, Peethambaran; Chembukave, Bhadra; Appu, Abhilash P; Vijayakumar, Nivetha; Moffett, John R; Puthillathu, Narayanan; Namboodiri, Aryan M A

2017-07-15

The intranasal route of administration has proven to be an effective method for bypassing the blood brain barrier and avoiding first pass hepatic metabolism when targeting drugs to the brain. Most small molecules gain rapid access to CNS parenchyma when administered intranasally. However, bioavailability is affected by various factors ranging from the molecular weight of the drug to the mode of intranasal delivery. We examined the effects of animal posture, intranasal application method and animal weight and age on the delivery of radiolabeled pralidoxime ( 3 H-2-PAM) to the brain of rats. We found that using upright vs. supine posture did not significantly affect 3 H-2-PAM concentrations in different brain regions. Older animals with higher weights required increased doses to achieve the same drug concentration throughout the brain when compared to young animals with lower body weights. The use of an intranasal aerosol propelled delivery device mainly increased bioavailability in the olfactory bulbs, but did not reliably increase delivery of the drug to various other brain regions, and in some regions of the brain delivered less of the drug than simple pipette administration. In view of the emerging interest in the use of intranasal delivery of drugs to combat cognitive decline in old age, we tested effectiveness in very old rats and found the method to be as effective in the older rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Fumigation in Ayurveda: potential strategy for drug discovery and drug delivery.

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Vishnuprasad, Chethala N; Pradeep, Nediyamparambu Sukumaran; Cho, Yong Woo; Gangadharan, Geethalayam Gopinathan; Han, Sung Soo

2013-09-16

Ayurveda has its unique perceptions and resultant methodologies for defining and treating human diseases. Fumigation therapy is one of the several treatment methods described in Ayurveda whereby fumes produced from defined drug formulations are inhaled by patients. This therapeutic procedure offers promising research opportunities from phytochemical and ethnopharmacological viewpoints, however, it remains under-noticed. Considering these facts, this review is primarily aimed at introducing said Ayurvedic fumigation therapy and discussing its scientific gaps and future challenges. A search of multiple bibliographical databases and traditional Ayurvedic text books was conducted and the articles analyzed under various key themes, e.g., Ayurvedic fumigation, fumigation therapy, medicinal fumigation, inhalation of drugs and aerosol therapy. Ayurveda recommends fumigation as a method of sterilization and therapeutic procedure for various human diseases including microbial infections and psychological disorders. However, it has not gained much attention as a prospective field with multiple research opportunities. It is necessary to have a more detailed and systematic investigation of the phytochemical and pharmacodynamic properties of Ayurvedic fumigation therapy in order to facilitate the identification of novel bioactive compounds and more effective drug administration methods. © 2013 Elsevier Ireland Ltd. All rights reserved.

Role of cytochrome P450 in drug interactions

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Bibi Zakia

2008-10-01

Full Text Available Abstract Drug-drug interactions have become an important issue in health care. It is now realized that many drug-drug interactions can be explained by alterations in the metabolic enzymes that are present in the liver and other extra-hepatic tissues. Many of the major pharmacokinetic interactions between drugs are due to hepatic cytochrome P450 (P450 or CYP enzymes being affected by previous administration of other drugs. After coadministration, some drugs act as potent enzyme inducers, whereas others are inhibitors. However, reports of enzyme inhibition are very much more common. Understanding these mechanisms of enzyme inhibition or induction is extremely important in order to give appropriate multiple-drug therapies. In future, it may help to identify individuals at greatest risk of drug interactions and adverse events.

Peer influences on drug self-administration: an econometric analysis in socially housed rats.

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Peitz, Geoffrey W; Strickland, Justin C; Pitts, Elizabeth G; Foley, Mark; Tonidandel, Scott; Smith, Mark A

2013-04-01

Social-learning theories of substance use propose that members of peer groups influence the drug use of other members by selectively modeling, reinforcing, and punishing either abstinence-related or drug-related behaviors. The objective of the present study was to examine the social influences on cocaine self-administration in isolated and socially housed rats, under conditions where the socially housed rats were tested simultaneously with their partner in the same chamber. To this end, male rats were obtained at weaning and housed in isolated or pair-housed conditions for 6 weeks. Rats were then implanted with intravenous catheters and cocaine self-administration was examined in custom-built operant conditioning chambers that allowed two rats to be tested simultaneously. For some socially housed subjects, both rats had simultaneous access to cocaine; for others, only one rat of the pair had access to cocaine. An econometric analysis was applied to the data, and the reinforcing strength of cocaine was measured by examining consumption (i.e. quantity demanded) and elasticity of demand as a function of price, which was manipulated by varying the dose and ratio requirements on a fixed ratio schedule of reinforcement. Cocaine consumption decreased as a function of price in all groups. Elasticity of demand did not vary across groups, but consumption was significantly lower in socially housed rats paired with a rat without access to cocaine. These data suggest that the presence of an abstaining peer decreases the reinforcing strength of cocaine, thus supporting the development of social interventions in drug abuse prevention and treatment programs.

Chronic Uridine Administration Induces Fatty Liver and Pre-Diabetic Conditions in Mice.

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Yasuyo Urasaki

Full Text Available Uridine is a pyrimidine nucleoside that exerts restorative functions in tissues under stress. Short-term co-administration of uridine with multiple unrelated drugs prevents drug-induced liver lipid accumulation. Uridine has the ability to modulate liver metabolism; however, the precise mechanism has not been delineated. In this study, long-term effects of uridine on liver metabolism were examined in both HepG2 cell cultures and C57BL/6J mice. We report that uridine administration was associated with O-GlcNAc modification of FOXO1, increased gluconeogenesis, reduced insulin signaling activity, and reduced expression of a liver-specific fatty acid binding protein FABP1. Long-term uridine feeding induced systemic glucose intolerance and severe liver lipid accumulation in mice. Our findings suggest that the therapeutic potentials of uridine should be designed for short-term acute administration.

Safe injection practices for administration of propofol.

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King, Cecil A; Ogg, Mary

2012-03-01

Sepsis and postoperative infection can occur as a result of unsafe practices in the administration of propofol and other injectable medications. Investigations of infection outbreaks have revealed the causes to be related to bacterial growth in or contamination of propofol and unsafe medication practices, including reuse of syringes on multiple patients, use of single-use medication vials for multiple patients, and failure to practice aseptic technique and adhere to infection control practices. Surveys conducted by AORN and other researchers have provided additional information on perioperative practices related to injectable medications. In 2009, the US Food and Drug Administration and the Centers for Disease Control and Prevention convened a group of clinicians to gain a better understanding of the issues related to infection outbreaks and injectable medications. The meeting participants proposed collecting data to persuade clinicians to adopt new practices, developing guiding principles for propofol use, and describing propofol-specific, site-specific, and practitioner-specific injection techniques. AORN provides resources to help perioperative nurses reduce the incidence of postoperative infection related to medication administration. Copyright © 2012 AORN, Inc. Published by Elsevier Inc. All rights reserved.

A stochastic model for the probability of malaria extinction by mass drug administration.

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Pemberton-Ross, Peter; Chitnis, Nakul; Pothin, Emilie; Smith, Thomas A

2017-09-18

Mass drug administration (MDA) has been proposed as an intervention to achieve local extinction of malaria. Although its effect on the reproduction number is short lived, extinction may subsequently occur in a small population due to stochastic fluctuations. This paper examines how the probability of stochastic extinction depends on population size, MDA coverage and the reproduction number under control, R c . A simple compartmental model is developed which is used to compute the probability of extinction using probability generating functions. The expected time to extinction in small populations after MDA for various scenarios in this model is calculated analytically. The results indicate that mass drug administration (Firstly, R c must be sustained at R c  95% to have a non-negligible probability of successful elimination. Stochastic fluctuations only significantly affect the probability of extinction in populations of about 1000 individuals or less. The expected time to extinction via stochastic fluctuation is less than 10 years only in populations less than about 150 individuals. Clustering of secondary infections and of MDA distribution both contribute positively to the potential probability of success, indicating that MDA would most effectively be administered at the household level. There are very limited circumstances in which MDA will lead to local malaria elimination with a substantial probability.

78 FR 76842 - Food and Drug Administration/American Academy of Ophthalmology Workshop on Developing Novel...

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2013-12-19

... 866-561-8558 (toll free). Food and beverages will be available for purchase by participants during the... accessible at http://www.regulations.gov . It may be viewed at the Division of Dockets Management, Food and... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001...

77 FR 56650 - Food and Drug Administration/American Glaucoma Society Workshop on the Validity, Reliability, and...

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2012-09-13

...] Food and Drug Administration/American Glaucoma Society Workshop on the Validity, Reliability, and... entitled ``FDA/American Glaucoma Society (AGS) Workshop on the Validity, Reliability, and Usability of... research. The purpose of this public workshop is to provide a forum for discussing the validity...

Occurrence of Anti-Drug Antibodies against Interferon-Beta and Natalizumab in Multiple Sclerosis

DEFF Research Database (Denmark)

Bachelet, Delphine; Hässler, Signe; Mbogning, Cyprien

2016-01-01

Immunogenicity of biopharmaceutical products in multiple sclerosis is a frequent side effect which has a multifactorial etiology. Here we study associations between anti-drug antibody (ADA) occurrence and demographic and clinical factors. Retrospective data from routine ADA test laboratories in S...

Prescriptive Oriented Drug Analysis of Multiple Sclerosis Disease by LC-UV in Whole Human Blood.

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Suneetha, A; Rajeswari, Raja K

2016-02-01

As a polytherapy treatment, multiple sclerosis disease demands prescriptions with more than one drug. Polytherapy is sometimes rational for drug combinations chosen to minimize adverse effects. Estimation of drugs that are concomitantly administered in polytherapy is acceptable as it shortens the analytical timepoints and also the usage of biological matrices. In clinical phase trials, the withdrawal of biofluids is a critical issue for each analysis. Estimating all the coadminsitered drugs in a single shot will be more effective and economical for pharmaceuticals. A single, simple, rapid and sensitive high-performance liquid chromatography assay method has been developed with UV detection and fully validated for the quantification of 14 drugs (at random combinations) used in the treatment of multiple sclerosis disease. The set of combinations was based on prescriptions to patients. Separations were achieved on an X-Terra MS C18 (100 × 3.9 mm, 5 µm) column. The analytes were extracted from 50 µL aliquots of whole human blood with protein precipitation using acetonitrile. All the drugs were sufficiently stable during storage for 24 h at room temperature and for 23 days at 2-8°C. The percentage recoveries of all drugs were between 90 and 115%, with RSD values <10.6%. This method has been shown to be reproducible and sensitive and can be applied to clinical samples from pharmacokinetic studies and also a useful tool in studying the drug interaction studies. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

One For All? Hitting multiple Alzheimer’s Disease targets with one drug

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Rebecca Ellen Hughes

2016-04-01

Full Text Available Alzheimer’s disease is a complex and multifactorial disease for which the mechanism is still not fully understood. As new insights into disease progression are discovered, new drugs must be designed to target those aspects of the disease that cause neuronal damage rather than just the symptoms currently addressed by single target drugs. It is becoming possible to target several aspects of the disease pathology at once using multi-target drugs. Intended as a introduction for non-experts, this review describes the key multi-target drug design approaches, namely structure-based, in silico, and data-mining, to evaluate what is preventing compounds progressing through the clinic to the market. Repurposing current drugs using their off-target effects reduces the cost of development, time to launch and also the uncertainty associated with safety and pharmacokinetics. The most promising drugs currently being investigated for repurposing to Alzheimer’s Disease are rasagiline, originally developed for the treatment of Parkinson’s Disease, and liraglutide, an antidiabetic. Rational drug design can combine pharmacophores of multiple drugs, systematically change functional groups, and rank them by virtual screening. Hits confirmed experimentally are rationally modified to generate an effective multi-potent lead compound. Examples from this approach are ASS234 with properties similar to rasagiline, and donecopride, a hybrid of an acetylcholinesterase inhibitor and a 5-HT4 receptor agonist with pro-cognitive effects. Exploiting these interdisciplinary approaches, public-private collaborative lead factories promise faster delivery of new drugs to the clinic.

Effect of co-administration of probiotics with polysaccharide based colon targeted delivery systems to optimize site specific drug release.

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Prudhviraj, G; Vaidya, Yogyata; Singh, Sachin Kumar; Yadav, Ankit Kumar; Kaur, Puneet; Gulati, Monica; Gowthamarajan, K

2015-11-01

Significant clinical success of colon targeted dosage forms has been limited by their inappropriate release profile at the target site. Their failure to release the drug completely in the colon may be attributed to changes in the colonic milieu because of pathological state, drug effect and psychological stress accompanying the diseased state or, a combination of these. Alteration in normal colonic pH and bacterial picture leads to incomplete release of drug from the designed delivery system. We report the effectiveness of a targeted delivery system wherein the constant replenishment of the colonic microbiota is achieved by concomitant administration of probiotics along with the polysaccharide based drug delivery system. Guar gum coated spheroids of sulfasalazine were prepared. In the dissolution studies, these spheroids showed markedly higher release in the simulated colonic fluid. In vivo experiments conducted in rats clearly demonstrated the therapeutic advantage of co-administration of probiotics with guar gum coated spheroids. Our results suggest that concomitant use of probiotics along with the polysaccharide based delivery systems can be a simple strategy to achieve satisfactory colon targeting of drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of sampling and diagnostic effort on the assessment of schistosomiasis and soil-transmitted helminthiasis and drug efficacy: a meta-analysis of six drug efficacy trials and one epidemiological survey.

Science.gov (United States)

Levecke, Bruno; Brooker, Simon J; Knopp, Stefanie; Steinmann, Peter; Sousa-Figueiredo, Jose Carlos; Stothard, J Russell; Utzinger, Jürg; Vercruysse, Jozef

2014-12-01

It is generally recommended to perform multiple stool examinations in order to improve the diagnostic accuracy when assessing the impact of mass drug administration programmes to control human intestinal worm infections and determining efficacy of the drugs administered. However, the collection and diagnostic work-up of multiple stool samples increases costs and workload. It has been hypothesized that these increased efforts provide more accurate results when infection and drug efficacy are summarized by prevalence (proportion of subjects infected) and cure rate (CR, proportion of infected subjects that become egg-negative after drug administration), respectively, but not when these indicators are expressed in terms of infection intensity and egg reduction rate (ERR). We performed a meta-analysis of six drug efficacy trials and one epidemiological survey. We compared prevalence and intensity of infection, CR and ERR based on collection of one or two stool samples that were processed with single or duplicate Kato-Katz thick smears. We found that the accuracy of prevalence estimates and CR was lowest with the minimal sampling effort, but that this was not the case for estimating infection intensity and ERR. Hence, a single Kato-Katz thick smear is sufficient for reporting infection intensity and ERR following drug treatment.

Radioprotective efficacy of dipyridamole and AMP combination in fractionated radiation regimen, and its dependence on the time of administration of the drugs prior to irradiation

International Nuclear Information System (INIS)

Hofer, M.; Pospisil, M.; Netikova, J.; Hola, J.; Znojil, V.; Vacha, J.

1995-01-01

The authors have recently demonstrated that a combined administration of dipyridamole and adenosine monophosphate to mice induces radioprotective effects in terms of postirradiation hematopoietic recovery in animals irradiated with a single dose. The aim of the present experiments was to investigate the radioprotective ability of the drug combination under conditions of fractionated radiation. It was shown that administration of the drugs either 15 or 60 min before each of the five daily 3-Gy doses of gamma radiation enhances hematopoietic recovery and survival of mice exposed to an additional 'top-up' dose of 3.5 Gy. Furthermore, it was ascertained that administration of the drugs 60 min prior to irradiation is more effective than administration of the drugs 15 min prior to irradiation. Due to the evidence that administration of the drugs 15 min prior to irradiation protects the organism mainly via mechanisms of systemic hypoxia while the pretreatment 60 min before irradiation avoids the role of hypoxia and mainly induces cell proliferation effects, the present results suggest a more protective role of mechanisms stimulating hematopoiesis under conditions of fractionated radiation. The data may provide a basis for more rational use of radioprotection in fractionated radiation techniques. (author) 1 tab., 1 fig., 25 refs

75 FR 74063 - Supplemental Funding Under the Food and Drug Administration's Convener of Active Medical Product...

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2010-11-30

... the program expansion including the availability of appropriate staff and sufficient funding. 4. The...] Supplemental Funding Under the Food and Drug Administration's Convener of Active Medical Product Surveillance... expansion of its Conference Cooperative Agreement Program (U13), awarded to the Engelberg Center for Health...

Will mass drug administration eliminate lymphatic filariasis? Evidence from northern coastal Tanzania.

Science.gov (United States)

Parker, Melissa; Allen, Tim

2013-07-01

This article documents understandings and responses to mass drug administration (MDA) for the treatment and prevention of lymphatic filariasis among adults and children in northern coastal Tanzania from 2004 to 2011. Assessment of village-level distribution registers, combined with self-reported drug uptake surveys of adults, participant observation and interviews, revealed that at study sites in Pangani and Muheza districts the uptake of drugs was persistently low. The majority of people living at these highly endemic locations either did not receive or actively rejected free treatment. A combination of social, economic and political reasons explain the low uptake of drugs. These include a fear of treatment (attributable, in part, to a lack of trust in international aid and a questioning of the motives behind the distribution); divergence between biomedical and local understandings of lymphatic filariasis; and limited and ineffective communication about the rationale for mass treatment. Other contributory factors are the reliance upon volunteers for distribution within villages and, in some locations, strained relationships between different groups of people within villages as well as between local leaders and government officials. The article also highlights a disjuncture between self-reported uptake of drugs by adults at a village level and the higher uptake of drugs recorded in official reports. The latter informs claims that elimination will be a possibility by 2020. This gives voice to a broader problem: there is considerable pressure for those implementing MDA to report positive results. The very real challenges of making MDA work are pushed to one side - adding to a rhetoric of success at the expense of engaging with local realities. It is vital to address the kind of issues raised in this article if current attempts to eliminate lymphatic filariasis in mainland coastal Tanzania are to achieve their goal.

A critical examination of the introduction of drug detection dogs for policing of illicit drugs in New South Wales, Australia using Kingdon’s ‘multiple streams’ heuristic

NARCIS (Netherlands)

Lancaster, Kari; Ritter, Alison; Hughes, Caitlin; Hoppe, Robertus

2017-01-01

This paper critically analyses the introduction of drug detection dogs as a tool for policing of illicit drugs in New South Wales, Australia. Using Kingdon’s ‘multiple streams’ heuristic as a lens for analysis, we identify how the issue of drugs policing became prominent on the policy agenda, and

Quantifying The Food And Drug Administration's rulemaking delays highlights the need for transparency.

Science.gov (United States)

Hwang, Thomas J; Avorn, Jerry; Carpenter, Daniel; Kesselheim, Aaron S

2014-02-01

The Food and Drug Administration (FDA) frequently uses its rulemaking process to establish or modify the way it regulates drugs, medical devices, and other medical products. The federal agency's rulemaking is controversial because of its perceived complexity, lack of transparency, and lengthy duration. To shed light on the FDA's rulemaking process, we examined the evolution of significant rules that the agency published during 2000-12 for drugs, devices, and other medical products. We found that the rules' median time to finalization was 7.3 years, with the pre-rule phase and postreview deliberation within the FDA accounting for the majority of that time. Rules that involved mandatory cost-benefit analyses were associated with an additional delay of approximately two years. We also found that longer review times were significantly associated with a reduction in the stringency of final rules, compared to the originally proposed versions. We recommend improving FDA's rulemaking by allocating additional resources to increase efficiency and by embarking on initiatives to promote transparency by the FDA and other parts of the executive branch.

Zolpidem prescribing practices before and after Food and Drug Administration required product labeling changes.

Science.gov (United States)

Norman, Jessica L; Fixen, Danielle R; Saseen, Joseph J; Saba, Laura M; Linnebur, Sunny A

2017-01-01

Women have higher morning serum zolpidem concentrations than men after taking an evening dose, potentially leading to increased risk of harm. On 19 April 2013, the United States Food and Drug Administration required labeling changes for zolpidem, recommending an initial dose of no greater than 5 mg (immediate release) or 6.25 mg (controlled release) per night in women. The primary objective of this study was to compare prescribing practices before and after the 2013 zolpidem labeling change. A secondary objective was to evaluate serious adverse events potentially related to zolpidem. Electronic medical records of adults receiving care through the University of Colorado Health system were accessed for study inclusion if patients were provided a first-time prescription for zolpidem either prior to or after the Food and Drug Administration labeling change. Patients were randomly chosen from eight strata based on age, gender, and date of zolpidem initiation (before/after the labeling change). Demographic and zolpidem prescribing data were collected. Low-dose zolpidem was considered 5 mg (immediate release) or 6.25 mg (controlled release) daily or less. Documentation of potentially related serious adverse events within the patients' records was also evaluated. A total of 400 patients were included in the study. The overall percentage of patients prescribed low-dose zolpidem increased from 44% to 58% after the labeling change (p = 0.0020). In a pre-specified subgroup analysis, the percentage of patients prescribed low-dose zolpidem increased in all groups, including young men (38%-50%, p = 0.23), elderly men (34%-40%, p = 0.53), and elderly women (60%-74%, p = 0.14), but the change was only significant in young women (42%-70%, p = 0.0045). After Food and Drug Administration-mandated labeling changes for zolpidem in 2013, the percentage of overall patients in our health system, and specifically young women, with initial prescriptions for low

Drug resistance in vectorborne parasites: multiple actors and scenarios for an evolutionary arms race.

Science.gov (United States)

Vanaerschot, Manu; Huijben, Silvie; Van den Broeck, Frederik; Dujardin, Jean-Claude

2014-01-01

Drug-resistant pathogens emerge faster than new drugs come out of drug discovery pipelines. Current and future drug options should therefore be better protected, requiring a clear understanding of the factors that contribute to the natural history of drug resistance. Although many of these factors are relatively well understood for most bacteria, this proves to be more complex for vectorborne parasites. In this review, we discuss considering three key models (Plasmodium, Leishmania and Schistosoma) how drug resistance can emerge, spread and persist. We demonstrate a multiplicity of scenarios, clearly resulting from the biological diversity of the different organisms, but also from the different modes of action of the drugs used, the specific within- and between-host ecology of the parasites, and environmental factors that may have direct or indirect effects. We conclude that integrated control of drug-resistant vectorborne parasites is not dependent upon chemotherapy only, but also requires a better insight into the ecology of these parasites and how their transmission can be impaired. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Neuropharmacological mechanisms of drug reward: beyond dopamine in the nucleus accumbens.

Science.gov (United States)

Bardo, M T

1998-01-01

Multiple lines of research have implicated the mesolimbic dopamine system in drug reward measured by either the drug self-administration or conditioned place preference paradigm. The present review summarizes recent work that examines the neuropharmacological mechanisms by which drugs impinge on this dopaminergic neural circuitry, as well as other systems that provide input and output circuits to the mesolimbic dopamine system. Studies examining the effect of selective agonist and antagonist drugs administered systemically have indicated that multiple neurotransmitters are involved, including dopamine, serotonin, acetylcholine, glutamate, GABA, and various peptides. Direct microinjection studies have also provided crucial evidence indicating that, in addition to the mesolimbic dopamine system, other structures play a role in drug reward, including the ventral pallidum, amygdala, hippocampus, hypothalamus, and pedunculopontine tegmental nucleus. GABAergic circuitry descending from the nucleus accumbens to the pedunculopontine tegmental nucleus via the ventral pallidum appears to be especially important in directing the behavioral sequelae associated with reward produced by various drugs of abuse. However, activation of the reward circuitry is achieved differently for various drugs of abuse. With amphetamine and cocaine, initiation of reward is controlled within the nucleus accumbens and prefrontal cortex, respectively. With opiates, initiation of reward involves the ventral tegmental area, nucleus accumbens, hippocampus, and hypothalamus. It is not clear presently if these multiple anatomical structures mediate opiate reward by converging on a single output system or multiple output systems.

Antithyroid drugs induced agranulocytosis and multiple myeloma: case report and general considerations.

Science.gov (United States)

Dănciulescu Miulescu, R; Carşote, M; Trifănescu, R; Ferechide, D; Poiană, C

2013-09-15

Antithyroid drugs as thionamides are largely used in the treatment of the thyrotoxicosis. Side effects were reported in less than 10% of the cases, especially hematological, hepatic or skin allergies. One of the most severe manifestations is agranulocytosis, probably based on an immune mechanism that is exacerbated by the presence of the thyroid autoimmune disease itself. If the presence of the severe leucopenia is actually an epiphenomenon of a preexisting hematological disturbance as multiple myeloma is debated. The myeloma may also be correlated with an autoimmune predisposition. We present the case of a 56 years old female patient diagnosed with Graves' disease, who developed agranulocytosis after 8 months of therapy with thiamazole. Two months after antithyroid drug's withdrawal, the granulocytes number increased and she received therapy with radioiodine. Two years later she came back for diffuse bone pain that turned out to be caused by a multiple myeloma, confirmed by bone marrow biopsy. It might be a connection between the severe form of leucopenia that the patient developed and the medullar malignancy.

A cloud on the horizon-a survey into the use of electronic vaping devices for recreational drug and new psychoactive substance (NPS) administration.

Science.gov (United States)

Blundell, M; Dargan, P; Wood, D

2018-01-01

There is limited published scientific data on vaping recreational drugs other than cannabis. A recent review suggested that 15% of people vaping cannabis have also vaped a synthetic cannabinoid receptor agonist (SCRA) and identified over 300 Internet reports of e-liquid manufacture of recreational drugs and/or new psychoactive substances (NPS). To determine the prevalence of use of electronic vaping devices for recreational drug and NPS delivery in the UK. A voluntary online survey using a convenience sample of UK adult participants (aged 16 years old and over) identified by a market research company. Data was collected regarding demographics, smoking history, electronic vaping device history and recreational drug/NPS use and route of administration. There were 2501 respondents. The mean (±SD) age was 46.2 ± 16.8 years old. The commonest lifetime recreational drug used was Cannabis (818, 32.7%). The majority of respondents had smoked (1545, 61.8%) with 731 (29.2%) being current smokers. The most commonly used SCRA product was 'Spice Gold' (173, 6.9%) and SCRA compound was ADB-CHMICA (48, 1.9%). 861 (34.4%) had used an electronic vaping device; 340 (13.6%) having used them for recreational drug administration; 236 (9.4%) reporting current use. The commonest lifetime recreational drug to be vaped was cannabis (155, 65.7%), with electronic cigarettes (230, 48.2%) being the commonest reported route of SCRA compound administration. 9.4% of respondents currently use electronic vaping devices for recreational drug administration with 6.2% reporting lifetime cannabis vaping use. Further larger scale studies are required to help inform the appropriate treatment and primary prevention strategies. © The Author 2017. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com

A Critical Examination of the Introduction of Drug Detection Dogs for Policing of Illicit Drugs in New South Wales, Australia Using Kingdon's "Multiple Streams" Heuristic

Science.gov (United States)

Lancaster, Kari; Ritter, Alison; Hughes, Caitlin; Hoppe, Robert

2017-01-01

This paper critically analyses the introduction of drug detection dogs as a tool for policing of illicit drugs in New South Wales, Australia. Using Kingdon's "multiple streams" heuristic as a lens for analysis, we identify how the issue of drugs policing became prominent on the policy agenda, and the conditions under which the…

Multiple and substitute addictions involving prescription drugs misuse among 12th graders: gateway theory revisited with Market Basket Analysis.

Science.gov (United States)

Jayawardene, Wasantha Parakrama; YoussefAgha, Ahmed Hassan

2014-01-01

This study aimed to identify the sequential patterns of drug use initiation, which included prescription drugs misuse (PDM), among 12th-grade students in Indiana. The study also tested the suitability of the data mining method Market Basket Analysis (MBA) to detect common drug use initiation sequences in large-scale surveys. Data from 2007 to 2009 Annual Surveys of Alcohol, Tobacco, and Other Drug Use by Indiana Children and Adolescents were used for this study. A close-ended, self-administered questionnaire was used to ask adolescents about the use of 21 substance categories and the age of first use. "Support%" and "confidence%" statistics of Market Basket Analysis detected multiple and substitute addictions, respectively. The lifetime prevalence of using any addictive substance was 73.3%, and it has been decreasing during past few years. Although the lifetime prevalence of PDM was 19.2%, it has been increasing. Males and whites were more likely to use drugs and engage in multiple addictions. Market Basket Analysis identified common drug use initiation sequences that involved 11 drugs. High levels of support existed for associations among alcohol, cigarettes, and marijuana, whereas associations that included prescription drugs had medium levels of support. Market Basket Analysis is useful for the detection of common substance use initiation sequences in large-scale surveys. Before initiation of prescription drugs, physicians should consider the adolescents' risk of addiction. Prevention programs should address multiple addictions, substitute addictions, common sequences in drug use initiation, sex and racial differences in PDM, and normative beliefs of parents and adolescents in relation to PDM.

Host-guest chemistry of dendrimer-drug complexes: 7. Formation of stable inclusions between acetylated dendrimers and drugs bearing multiple charges.

Science.gov (United States)

Fang, Min; Zhang, Jiahai; Wu, Qinglin; Xu, Tongwen; Cheng, Yiyun

2012-03-15

Drug molecules bearing multiple charges usually form precipitates with cationic dendrimers, which presents a challenge during the preparation of dendrimer inclusions for these drugs. In the present study, fully acetylated polyamidoamine (PAMAM) dendrimers were proposed as stable vehicles for drug molecules bearing two negative charges such as Congo red and indocyanine green. NMR techniques including (1)H NMR and (1)H-(1)H NOESY were used to characterize the host-guest chemistry of acetylated dendrimer and these guest molecules. The cationic PAMAM dendrimer was found to form a precipitate with Congo red and indocyanine green, but the acetylated one avoided the formation of cross-linking structures in aqueous solutions. NOESY studies revealed the encapsulation of Congo red and indocyanine green within the interior cavities of PAMAM dendrimers at mild acidic conditions and acetylated dendrimers show much stronger ability to encapsulate the guest molecules than cationic ones. Also, UV-vis-NIR studies suggest that acetylated dendrimers significantly improve the photostability of indocyanine green and prevent the formation of indocyanine green J-aggregates in aqueous solutions. The present study provides a new insight into dendrimer-based host-guest systems, especially for those guest molecules bearing multiple charges. © 2012 American Chemical Society

[Oral treatments in multiple sclerosis].

Science.gov (United States)

Meca-Lallana, José Eustasio; Hernández-Clares, Rocío; Carreón-Guarnizo, Ester

2014-12-01

The development of new disease-modifying drugs (DMD) in relapsing-remitting multiple sclerosis (RRMS), which share the common denominator of oral administration, considerably improves patient expectations in terms of effectiveness, tolerability and treatment adherence compared with currently available drugs. However, the common route of administration of these drugs does not mean that they are equivalent, since the heading of "oral route" encompasses drugs with distinct indications and mechanisms of action, as well as heterogeneous results in terms of efficacy and safety, allowing treatment to be personalized according to the each patient' s characteristics. Currently, four oral DMD are available or in an advanced stage of clinical development: fingolimod, teriflunomide, dimethyl fumarate and laquinimod. In pivotal trials versus placebo, these molecules reduced the annualized rate of exacerbations versus placebo by 54%, 31%, 53% and 23%, respectively, the risk of progression of disability by 31%, 30%, 38% and 36%, and the number of active lesions showing contrast uptake on magnetic resonance imaging by 82%, 80%, 90% and 37%, respectively. Based on the risk/benefit ratio, fingolimod is indicated in patients with suboptimal response to initial DMD or in severe rapidly progressing RRMS, while the remaining drugs can be used as first-line options. Clinical experience with these treatments will provide new data on safety and effectiveness, which will be determinant when establishing therapeutic algorithms. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Patients’ satisfaction with and views about treatment with disease-modifying drugs in multiple sclerosis

Directory of Open Access Journals (Sweden)

Caroline Vieira Spessotto

2016-08-01

Full Text Available ABSTRACT Objective The treatment of multiple sclerosis (MS with disease-modifying-drugs (DMDs is evolving and new drugs are reaching the market. Efficacy and safety aspects of the drugs are crucial, but the patients’ satisfaction with the treatment must be taken into consideration. Methods Individual interview with patients with MS regarding their satisfaction and points of view on the treatment with DMDs. Results One hundred and twenty eight patients attending specialized MS Units in five different cities were interviewed. Over 80% of patients were very satisfied with the drugs in use regarding convenience and perceived benefits. The only aspect scoring lesser values was tolerability. Conclusion Parameters for improving treatment in MS must include efficacy, safety, and patient satisfaction with the given DMD.

75 FR 32482 - Investigational New Drug Applications; Co-development of Investigational Drugs

Science.gov (United States)

2010-06-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0247] Investigational New Drug Applications; Co-development of Investigational Drugs AGENCY: Food and Drug Administration, HHS. ACTION: Notice; establishment of docket; request for comments. SUMMARY: The Food and Drug...

78 FR 34392 - Guidance for Industry and Food and Drug Administration Staff: Technical Considerations for Pen...

Science.gov (United States)

2013-06-07

... adhesive label to assist the office in processing your requests. The guidance may also be obtained by mail... and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. FOR FURTHER INFORMATION... June 2013. FDA is providing this final guidance document to assist industry in developing technical and...

Concurrent administration of anticancer chemotherapy drug and herbal medicine on the perspective of pharmacokinetics

OpenAIRE

Yung-Yi Cheng; Chen-Hsi Hsieh; Tung-Hu Tsai

2018-01-01

With an increasing number of cancer patients seeking an improved quality of life, complementary and alternative therapies are becoming more common ways to achieve such improvements. The potential risks of concurrent administration are serious and must be addressed. However, comprehensive evidence for the risks and benefits of combining anticancer drugs with traditional herbs is rare. Pharmacokinetic investigations are an efficient way to understand the influence of concomitant remedies. There...

Recent advances in understanding multiple myeloma [version 1; referees: 4 approved

Directory of Open Access Journals (Sweden)

Binod Dhakal

2016-08-01

Full Text Available There have been major recent advancements in the understanding and management of multiple myeloma. Diagnostic criteria have been revised and former ultra-high-risk smoldering multiple myeloma is now considered multiple myeloma in need of treatment. Understanding clonal progression, evolution, and tides not only has helped elucidate the disease behavior but might help expand therapeutic choices in order to select appropriate treatment for patients. Unprecedented response rates with modern triplet induction therapies containing proteasome inhibitor and immunomodulators have made this approach standard for initial treatment. The US Food and Drug Administration approved four new drugs (two targeted antibodies and two oral agents in 2015 in relapsed/refractory multiple myeloma and these drugs along with the other already-available drugs have now increased the choices of regimens. Even drugs without single-agent activity, such as panobinostat and elotuzumab, have an important role, especially in the proteasome inhibitor refractory setting. Recent studies done in the context of novel agent induction suggest that high-dose therapy followed by autologous transplant continues to improve response rates and progression-free survival, thus underscoring their role in transplant-eligible patients. Evolving paradigms in the treatment of multiple myeloma include newer promising immune approaches, such as adoptive cellular therapies, vaccines, or antibody-based immune manipulations. Though multiple myeloma is still considered incurable, it is clear that with the improved understanding of disease biology and clonal architecture of relapse combined with the availability of multi-targeted approaches, we are ever closer to a lasting cure or transformation into indolent and long-lasting disease courses or both.

The development of multiple drug use among anabolic-androgenic steroid users: six subjective case reports

Directory of Open Access Journals (Sweden)

Nyberg Fred

2008-11-01

Full Text Available Abstract Background The inappropriate use of anabolic androgenic steroids (AAS was originally a problem among athletes but AAS are now often used in nonsport situations and by patients attending regular addiction clinics. The aim of this study was to improve understanding of the development of multiple drug use in patients seeking treatment at an addiction clinic for AAS-related problems. Methods We interviewed six patients (four men and two women with experience of AAS use who were attending an addiction clinic for what they believed were AAS-related problems. The patients were interviewed in-depth about their life stories, with special emphasis on social background, substance use, the development of total drug use and subjective experienced psychological and physical side effects. Results There was significant variation in the development of drug use in relation to social background, onset of drug use, relationship to AAS use and experience of AAS effects. All patients had initially experienced positive effects from AAS but, over time, the negative experiences had outweighed the positive effects. All patients were dedicated to excess training and took AAS in combination with gym training, indicating that the use of these drugs is closely related to this form of training. Use of multiple drugs was common either in parallel with AAS use or serially. Conclusion The study shows the importance of understanding how AAS use can develop either with or without the concomitant use of other drugs of abuse. The use of AAS can, however, progress to the use of other drugs. The study also indicates the importance of obtaining accurate, comprehensive information about the development of AAS use in designing treatment programmes and prevention strategies in this area.

Elimination of cetirizine following administration of multiple doses to exercised thoroughbred horses.

Science.gov (United States)

Knych, H K; Stanley, S D; Arthur, R M; McKemie, D S

2016-10-01

Cetirizine is an antihistamine used in performance horses for the treatment of hypersensitivity reactions and as such a withdrawal time is necessary prior to competition. The objective of the current study was to describe the disposition and elimination of cetirizine following oral administration in order to provide additional serum concentration data upon which appropriate regulatory recommendations can be established. Nine exercised thoroughbred horses were administered 0.4 mg/kg of cetirizine orally BID for a total of five doses. Blood samples were collected immediately prior to drug administration and at various times postadministration. Serum cetirizine concentrations were determined and selected pharmacokinetic parameters determined. The serum elimination half-life was 5.83 ± 0.841 h. Average serum cetirizine concentrations were still above the LOQ of the assay (0.05 ng/mL) at 48 h (final sample collected) postadministration of the final dose. © 2016 John Wiley & Sons Ltd.

Accelerated approval of oncology products: the food and drug administration experience.

Science.gov (United States)

Johnson, John R; Ning, Yang-Min; Farrell, Ann; Justice, Robert; Keegan, Patricia; Pazdur, Richard

2011-04-20

We reviewed the regulatory history of the accelerated approval process and the US Food and Drug Administration (FDA) experience with accelerated approval of oncology products from its initiation in December 11, 1992, to July 1, 2010. The accelerated approval regulations allowed accelerated approval of products to treat serious or life-threatening diseases based on surrogate endpoints that are reasonably likely to predict clinical benefit. Failure to complete postapproval trials to confirm clinical benefit with due diligence could result in removal of the accelerated approval indication from the market. From December 11, 1992, to July 1, 2010, the FDA granted accelerated approval to 35 oncology products for 47 new indications. Clinical benefit was confirmed in postapproval trials for 26 of the 47 new indications, resulting in conversion to regular approval. The median time between accelerated approval and regular approval of oncology products was 3.9 years (range = 0.8-12.6 years) and the mean time was 4.7 years, representing a substantial time savings in terms of earlier availability of drugs to cancer patients. Three new indications did not show clinical benefit when confirmatory postapproval trials were completed and were subsequently removed from the market or had restricted distribution plans implemented. Confirmatory trials were not completed for 14 new indications. The five longest intervals from receipt of accelerated approval to July 1, 2010, without completion of trials to confirm clinical benefit were 10.5, 6.4, 5.5, 5.5, and 4.7 years. The five longest intervals between accelerated approval and successful conversion to regular approval were 12.6, 9.7, 8.1, 7.5, and 7.4 years. Trials to confirm clinical benefit should be part of the drug development plan and should be in progress at the time of an application seeking accelerated approval to prevent an ineffective drug from remaining on the market for an unacceptable time.

Stress modulation of drug self-administration: implications for addiction comorbidity with post-traumatic stress disorder

Science.gov (United States)

Logrip, Marian L.; Zorrilla, Eric P.; Koob, George F.

2011-01-01

Drug abuse and dependence present significant health burdens for our society, affecting roughly 10% of the population. Stress likely contributes to the development and persistence of drug use; for example, rates of substance dependence are elevated among individuals diagnosed with post-traumatic stress disorder (PTSD). Thus, understanding the interaction between stress and drug use, and associated neuroadaptations, is key for developing therapies to combat substance use disorders. For this purpose, many rodent models of the effects of stress exposure on substance use have been developed; the models can be classified according to three categories of stress exposure: developmental, adult nonsocial, and adult social. The present review addresses preclinical findings on the effect of each type of trauma on responses to and self-administration of drugs of abuse by focusing on a key exemplar for each category. In addition, the potential efficacy of targeting neuropeptide systems that have been implicated in stress responses and stress system neuroadaptation in order to treat comorbid PTSD and substance abuse will be discussed. PMID:21782834

The effect of site (deltoid or gluteus muscle of intramuscular administration of anaesthetic drugs on the course of immobilisation in macaque monkeys (Macaca mulatta

Directory of Open Access Journals (Sweden)

Ladislav Hess

2012-01-01

Full Text Available The aim of this work was to study the effect of site of intramuscular administration of anaesthetic drugs on the course of immobilisation in macaque monkeys (Macaca mulatta. Twenty macaque monkeys were given medetomidine (25 µg·kg-1 and ketamine (3 mg·kg-1 intramuscularly to the deltoid (n = 10 animals or gluteus (n = 10 animals muscles. Behavioural changes, loss of aggressiveness, immobilisation time and cardiorespiratory changes were recorded. The effect of drugs was reversed after 20 min by i.m. administration of atipamezole at the dose of 250 µg·kg-1. Highly significant differences (P < 0.001 were found between groups with gluteal or deltoid administration of drugs on the onset of immobilisation effect (71.3 s and 108.3 s, respectively, and immobilisation time (152.7 s and 254.4 s, respectively. In the gluteus muscle group, the grasp reflex was still present at the beginning of immobilisation and slowly wore off in 15–45 s. The same was valid for muscle tone. There were no differences in cardiorespiratory parameters in any of the groups. Animals of both groups recovered in 3–6 min after atipamezole administration. Administration of drugs to the deltoid muscle resulted in a more rapid onset and increased effect of immobilisation than administration to the gluteus muscle. Both in veterinary and human medicine, injection to the deltoid muscle may be more convenient in all cases, when rapid and more prominent effect is desirable as in premedication before surgery or in emergency medicine. The study is the first to compare the effect of administering drugs to different muscles and the results may improve the practice of intramuscular injections in animals and in humans.

77 FR 16036 - Guidance for Industry, Third Parties and Food and Drug Administration Staff; Medical Device ISO...

Science.gov (United States)

2012-03-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0226...) audit report provides FDA a degree of assurance of compliance with basic and fundamental quality management system requirements for medical devices. \\1\\ The GHTF founding members auditing systems include...

Factors associated with prescribing restriction on oncology formulary drugs in Malaysia.

Science.gov (United States)

Fatokun, Omotayo; Olawepo, Michael N

2016-10-01

Background Drugs listed on formularies are often subjected to a variety of utilization restriction measures. However, the degree of restriction is influenced by multiple factors, including the characteristics and attributes of the listed drugs. Objective To identify the factors that are associated with the levels of prescribing restriction on oncology formulary drugs in Malaysia. Setting Oncology formulary in Malaysia. Method The Malaysia Drug Code assigned to each of the drug products on the Malaysia Ministry of Health (MOH) drug formulary was used to identify oncology drugs belonging to WHO ATC class L (antineoplastic and immunomodulating agents). Main outcome measures Categories of prescribing restrictions, therapeutic class, drug type, administration mode, number of sources and the post-approval use period. Results Oncology drugs having a shorter post-approval use period (p Malaysia MOH drug formulary.

Physico-chemical Stability of MabThera Drug-product Solution for Subcutaneous Injection under in-use Conditions with Different Administration Materials.

Science.gov (United States)

Mueller, Claudia; Dietel, Elke; Heynen, Severin R; Nalenz, Heiko; Goldbach, Pierre; Mahler, Hanns-Christian; Schmidt, Johannes; Grauschopf, Ulla; Schoenhamnmer, Karin

2015-01-01

MabThera is an essential component of the standard-of-care regimens in the treatment of non-Hodgkin lymphoma and Chronic Lymphatic Leukemia. MabThera for subcutaneous injection is a novel line extension that has been approved by the European Medicines Agency for the treatment of patients with follicular lymphoma and diffuse large B-cell lymphoma. This study aimed to evaluate in-use stability data of MabThera subcutaneous drug-product solution in single-use syringes for subcutaneous administration according to the European Medicines Agency guideline. The drug-product solution was exposed to material contact surfaces of five different administration setups commonly used in subcutaneous drug delivery. MabThera subcutaneous was transferred under aseptic conditions into polypropylene and polycarbonate syringes and stored for 1, 2, and 4 weeks at 2°C to 8°C followed by 24 hours at 30°C. After storage, subcutaneous administration was simulated and MabThera subcutaneous drug-product solution quality attributes were evaluated by using compendial physico-chemical tests, as well as suitable and validated molecule- and formulation-specific analytical methods. MabThera subcutaneous vials were treated and analyzed in parallel. The physico-chemical results of MabThera subcutaneous in the different setups were comparable to the control for all timepoints. No change in drug-product quality after storage and simulated administration was found compared to the control. However, since single-dose products do not contain preservatives, microbial contamination and growth needs to be avoided and product sterility needs to be ensured. The results showed that MabThera subcutaneous remains compatible and stable, from a physico-chemical perspective, for up to 4 weeks at 2°C to 8°C followed by 24 hours at 30°C with the contact materials tested in this study. In order to avoid and minimize microbial growth, MabThera subcutaneous should be used immediately after removal from the original

Pharmacokinetic and pharmacodynamic herb-drug interaction of Andrographis paniculata (Nees) extract and andrographolide with etoricoxib after oral administration in rats.

Science.gov (United States)

Balap, Aishwarya; Atre, Bhagyashri; Lohidasan, Sathiyanarayanan; Sinnathambi, Arulmozhi; Mahadik, Kakasaheb

2016-05-13

Andrographis paniculata Nees (Acanthacae) is commonly used medicinal plant in the traditional. Unani and Ayurvedic medicinal systems. It has broad range of pharmacological effects such as hepatoprotective, antioxidant, antivenom, antifertility, inhibition of replication of the HIV virus, antimalarial, antifungal, antibacterial, antidiabetic, suppression of various cancer cells and anti-inflammatory properties. Andrographolide (AN) is one of the active constituent of the A. paniculata Nees extract (APE). They have been found in many traditional herbal formulations in India and proven to be effective as anti-inflammatory drug To evaluate the pharmacokinetic and pharmacodynamic (anti-arthritic) herb-drug interactions of A. paniculata Nees extract (APE) and pure andrographolide (AN) with etoricoxib (ETO) after oral co-administration in wistar rats. After oral co-administration of APE (200mg/Kg) and AN (60mg/kg) with ETO (10mg/kg) in rats, drug concentrations in plasma were determined using HPLC method. The main pharmacokinetic parameters of Cmax, tmax, t1/2, MRT, Vd, CL, and AUC were calculated by non-compartment model. Change in paw volume, mechanical nociceptive threshold, mechanical hyperalgesia, histopathology and hematological parameters were evaluated to study antiarthritic activity. Co-administration of ETO with APE and pure AN decreased systemic exposure level of each compound in vivo. The Cmax, AUC, t1/2 of ETO was decreased whereas Vd and CL of ETO was increased significantly after co-administration of ETO with pure AN and APE. In pharmacodynamic study, ETO alone and ETO+APE (10+200mg/kg) groups exhibited significant synergistic anti-arthritic activity as compared to groups ETO+AN, APE and AN alone. The results obtained from this study suggested that ETO, APE and pure AN existed pharmacokinetic herb-drug interactions in rat which is correlated with anti-arthritic study. Physicians and patients using A. paniculata should have the knowledge about its possible

21 CFR 1316.13 - Frequency of administrative inspections.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Frequency of administrative inspections. 1316.13 Section 1316.13 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE ADMINISTRATIVE... as circumstances may require, based in part on the registrant's history of compliance with the...

77 FR 44256 - Draft Guidance for Industry and Food and Drug Administration Staff; Safety Considerations for 510...

Science.gov (United States)

2012-07-27

...] Draft Guidance for Industry and Food and Drug Administration Staff; Safety Considerations for 510(k... serious and sometimes fatal consequences to patients. This guidance provides recommendations to 510(k... unintended connections between enteral and nonenteral devices. This draft guidance is not final nor is it in...

76 FR 5387 - Guidance for Industry and Food and Drug Administration Staff; “`Harmful and Potentially Harmful...

Science.gov (United States)

2011-01-31

... of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville... harmful constituents, including smoke constituents, to health in each tobacco product by brand and by quantity in each brand and subbrand.'' The guidance discusses the meaning of the term ``harmful and...

76 FR 22905 - Guidance for Food and Drug Administration Staff and Tobacco Retailers on Civil Money Penalties...

Science.gov (United States)

2011-04-25

...] Guidance for Food and Drug Administration Staff and Tobacco Retailers on Civil Money Penalties and No... entitled ``Civil Money Penalties and No- Tobacco-Sale Orders for Tobacco Retailers.'' This guidance document describes FDA's current policies with respect to civil money penalties and no-tobacco-sale orders...

75 FR 53316 - Draft Guidance for Food and Drug Administration Staff and Tobacco Retailers on Civil Money...

Science.gov (United States)

2010-08-31

...] Draft Guidance for Food and Drug Administration Staff and Tobacco Retailers on Civil Money Penalties and... guidance entitled ``Civil Money Penalties and No-Tobacco-Sale Orders for Tobacco Retailers.'' This guidance document is intended to describe FDA's current policies with respect to civil money penalties and no...

Nuclear methods for food analysis at the U.S. Food and Drug Administration

International Nuclear Information System (INIS)

Anderson, D.L.; Cunningham, W.C.; Capar, S.G.; Baratta, E.J.; Mackill, P.

2001-01-01

An overview radioanalytical techniques used in support of research, monitoring programs, and field assignments directed by the U.S. Food and Drug Administration's Center for Food Safety and Applied Nutrition (CFSAN) is presented. The Winchester Engineering and Analytical Center annually determines radionuclide concentrations in 260 Total Diet Study foods, approximately 80 imported foods, and a selection of domestic foods collected near U.S. nuclear power plants. Radioanalytical techniques used at CFSAN's neutron analysis laboratory at the National Institute of Standards and Technology are discussed along with applications for research, quality control, and special projects. (author)

Adverse events reported to the Food and Drug Administration from 2004 to 2016 for cosmetics and personal care products marketed to newborns and infants.

Science.gov (United States)

Cornell, Erika; Kwa, Michael; Paller, Amy S; Xu, Shuai

2018-03-01

Despite their ubiquitous use and several recent health controversies involving cosmetics and personal care products for children, the Food and Drug Administration has little oversight of these products and relies on consumer-submitted adverse event reports. We assessed the recently released Center for Food Safety and Applied Nutrition's Adverse Event Reporting System database for adverse event reports submitted to the Food and Drug Administration for baby personal care products and to determine whether useful insights can be derived. We extracted the Center for Food Safety and Applied Nutrition's Adverse Event Reporting System data file from 2004 to 2016 and examined the subset classified according to the Food and Drug Administration-designated product class as a baby product. Events were manually categorized into product type and symptom type to assess for trends. Only 166 total adverse events were reported to the Food and Drug Administration for baby products from 2004 to 2016. The majority of reports indicated rash or other skin reaction; 46% of reported events led to a health care visit. Pediatric dermatologists should consider submitting cosmetics and personal care product adverse event reports and encouraging consumers to do so likewise in situations in which a product adversely affects a child's health. © 2018 Wiley Periodicals, Inc.

Mass drug administration for trachoma: how long is not long enough?

Directory of Open Access Journals (Sweden)

Violeta Jimenez

2015-03-01

Full Text Available Blinding trachoma is targeted for elimination by 2020 using the SAFE strategy (Surgery, Antibiotics, Facial cleanliness, and Environmental improvements. Annual mass drug administration (MDA with azithromycin is a cornerstone of this strategy. If baseline prevalence of clinical signs of trachomatous inflammation - follicular among 1-9 year-olds (TF1-9 is ≥ 10% but 30%, 7 or more annual MDAs may be required to achieve the target. There are five years left before the 2020 deadline to eliminate blinding trachoma. Low endemic settings are poised to succeed in their elimination goals. However, newly-identified high prevalence districts warrant immediate inclusion in the global program. Intensified application of the SAFE strategy is needed in order to guarantee blinding trachoma elimination by 2020.

Effective multiple oral administration of reverse genetics engineered infectious bursal disease virus in mice in the presence of neutralizing antibodies.

Science.gov (United States)

Hornyák, Ákos; Lipinski, Kai S; Bakonyi, Tamás; Forgách, Petra; Horváth, Ernő; Farsang, Attila; Hedley, Susan J; Palya, Vilmos; Bakács, Tibor; Kovesdi, Imre

2015-01-01

Despite spectacular successes in hepatitis B and C therapies, severe hepatic impairment is still a major treatment problem. The clinically tested infectious bursal disease virus (IBDV) superinfection therapy promises an innovative, interferon-free solution to this great unmet need, provided that a consistent manufacturing process preventing mutations or reversions to virulent strains is obtained. To address safety concerns, a tissue culture adapted IBDV vaccine strain V903/78 was cloned into cDNA plasmids ensuring reproducible production of a reverse engineered virus R903/78. The therapeutic drug candidate was characterized by immunocytochemistry assay, virus particle determination and immunoblot analysis. The biodistribution and potential immunogenicity of the IBDV agent was determined in mice, which is not a natural host of this virus, by quantitative detection of IBDV RNA by a quantitative reverse transcriptase-polymerase chain reaction and virus neutralization test, respectively. Several human cell lines supported IBDV propagation in the absence of visible cytopathic effect. The virus was stable from pH 8 to pH 6 and demonstrated significant resistance to low pH and also proved to be highly resistant to high temperatures. No pathological effects were observed in mice. Single and multiple oral administration of IBDV elicited antibodies with neutralizing activities in vitro. Repeat oral administration of R903/78 was successful despite the presence of neutralizing antibodies. Single oral and intravenous administration indicated that IBDV does not replicate in mammalian liver alleviating some safety related concerns. These data supports the development of an orally delivered anti-hepatitis B virus/ anti-hepatitis C virus viral agent for human use. Copyright © 2015 John Wiley & Sons, Ltd.

78 FR 47712 - Food and Drug Administration Modernization Act of 1997: Modifications to the List of Recognized...

Science.gov (United States)

2013-08-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2004-N-0451... should review the supplementary information sheet for the standard to understand fully the extent to... incorporating medical devices--Part 2-2: Guidance 2012-07 for the disclosure and communication of medical device...

Concanavalin-A conjugated fine-multiple emulsion loaded with 6-mercaptopurine.

Science.gov (United States)

Khopade, A J; Jain, N K

2000-01-01

Fine-multiple (water-in-oil-in-water) emulsions were prepared by two-step emulsification using sonication. They were coated with concanavalin-A (Con-A) by three methods. The one involving covalent coupling of Con-A to the multiple emulsion incorporated anchor was better compared with lipid derivatized Con-A anchoring or the glutaraldehyde-based cross-linking method, as shown by the faster rate of dextran-induced aggregation. The selected multiple emulsions were characterized by physical properties such as droplet size, encapsulation efficiency, and zeta potential. Stability parameters such as droplet size, creaming, leakage, and aggregation as a function of relative turbidity were monitored over a 1-month period, which revealed good stability of the formulations. The release profile of 6-mercaptopurine followed zero-order kinetics. Pharmacokinetic studies showed an increase in half-life and bioavailability from multiple emulsion formulations administered intravenously. There was prolonged retention of drug in various tissues of rats when treated with Con-A-coated multiple emulsion as compared with uncoated one. Our study demonstrates the suitability of fine-multiple emulsion for intravenous administration and the potential for prolonged retention of drugs and targeting in biological systems.

The acceptability of mass administrations of anti-malarial drugs as part of targeted malaria elimination in villages along the Thai–Myanmar border

Directory of Open Access Journals (Sweden)

Ladda Kajeechiwa

2016-09-01

Full Text Available Abstract Background A targeted malaria elimination project, including mass drug administrations (MDA of dihydroartemisinin/piperaquine plus a single low dose primaquine is underway in villages along the Thailand Myanmar border. The intervention has multiple components but the success of the project will depend on the participation of the entire communities. Quantitative surveys were conducted to study reasons for participation or non-participation in the campaign with the aim to identify factors associated with the acceptance and participation in the mass drug administrations. Methods The household heads in four study villages in which MDAs had taken place previously were interviewed between January 2014 and July 2015. Results 174/378 respondents (46 % completed three rounds of three drug doses each, 313/378 (83 % took at least three consecutive doses and 56/378 (15 % did not participate at all in the MDA. The respondents from the two villages (KNH and TPN were much more likely to participate in the MDA than respondents from the other two villages (HKT and TOT. The more compliant villages KNH and TPN had both an appearance of cohesive communities with similar demographic and ethnic backgrounds. By contrast the villages with low participation were unique. One village was fragmented following years of armed conflict and many respondents gave little inclination to cooperate with outsiders. The other village with low MDA coverage was characterised by a high percentage of short-term residents with little interest in community interventions. A universal reason for non-participation in the MDA applicable to all villages was an inadequate understanding of the intervention. Conclusions It is unlikely that community engagement can unite fragmented communities in participating in an intervention, which benefits the community. Understanding the purpose and the reasons underlying the intervention is an important pre-condition for participation. In the

Nephrogenic systemic fibrosis and class labeling of gadolinium-based contrast agents by the Food and Drug Administration.

Science.gov (United States)

Yang, Lucie; Krefting, Ira; Gorovets, Alex; Marzella, Louis; Kaiser, James; Boucher, Robert; Rieves, Dwaine

2012-10-01

In 2007, the Food and Drug Administration requested that manufacturers of all approved gadolinium-based contrast agents (GBCAs), drugs widely used in magnetic resonance imaging, use nearly identical text in their product labeling to describe the risk of nephrogenic systemic fibrosis (NSF). Accumulating information about NSF risks led to revision of the labeling text for all of these drugs in 2010. The present report summarizes the basis and purpose of this class-labeling approach and describes some of the related challenges, given the evolutionary nature of the NSF risk evidence. The class-labeling approach for presentation of product risk is designed to decrease the occurrence of NSF and to enhance the safe use of GBCAs in radiologic practice. © RSNA, 2012.

Chiron Vision files FDA application to market intraocular implant for CMV retinitis. Food and Drug Administration.

Science.gov (United States)

1995-07-01

Chiron Corporation and Hoffman-LaRoche announced a filing of a New Drug Application with the Food and Drug Administration (FDA) to market Vitrasert, its intraocular implant which delivers ganciclovir directly to the eye for treatment of CMV retinitis. Clinical trials show that Vitrasert offers a clinical improvement versus intravenous ganciclovir in further delaying progression of CMV retinitis in the treated eye. One study reported that the median time to progression of CMV retinitis was 186 days for eyes receiving Vitrasert compared to 72 days for eyes receiving intravenous ganciclovir therapy. Chiron's intraocular implant contains ganciclovir embedded in a polymer-based system that slowly releases the drug into the eye for up to eight months. Two additional trials are underway. For further information contact the Professional Services Group at Chiron Corporation at (800) 244-7668, select 2.

Nanoformulations of Rilpivirine for Topical Pericoital and Systemic Coitus-Independent Administration Efficiently Prevent HIV Transmission

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Date, Abhijit A.; Long, Julie M.; Nochii, Tomonori; Belshan, Michael; Shibata, Annemarie; Vincent, Heather; Baker, Caroline E.; Thayer, William O.; Kraus, Guenter; Lachaud-Durand, Sophie; Williams, Peter; Destache, Christopher J.; Garcia, J. Victor

2015-01-01

Vaginal HIV transmission accounts for the majority of new infections worldwide. Currently, multiple efforts to prevent HIV transmission are based on pre-exposure prophylaxis with various antiretroviral drugs. Here, we describe two novel nanoformulations of the reverse transcriptase inhibitor rilpivirine for pericoital and coitus-independent HIV prevention. Topically applied rilpivirine, encapsulated in PLGA nanoparticles, was delivered in a thermosensitive gel, which becomes solid at body temperature. PLGA nanoparticles with encapsulated rilpivirine coated the reproductive tract and offered significant protection to BLT humanized mice from a vaginal high-dose HIV-1 challenge. A different nanosuspension of crystalline rilpivirine (RPV LA), administered intramuscularly, protected BLT mice from a single vaginal high-dose HIV-1 challenge one week after drug administration. Using transmitted/founder viruses, which were previously shown to establish de novo infection in humans, we demonstrated that RPV LA offers significant protection from two consecutive high-dose HIV-1 challenges one and four weeks after drug administration. In this experiment, we also showed that, in certain cases, even in the presence of drug, HIV infection could occur without overt or detectable systemic replication until levels of drug were reduced. We also showed that infection in the presence of drug can result in acquisition of multiple viruses after subsequent exposures. These observations have important implications for the implementation of long-acting antiretroviral formulations for HIV prevention. They provide first evidence that occult infections can occur, despite the presence of sustained levels of antiretroviral drugs. Together, our results demonstrate that topically- or systemically administered rilpivirine offers significant coitus-dependent or coitus-independent protection from HIV infection. PMID:26271040

Synaptic plasticity in drug reward circuitry.

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Winder, Danny G; Egli, Regula E; Schramm, Nicole L; Matthews, Robert T

2002-11-01

Drug addiction is a major public health issue worldwide. The persistence of drug craving coupled with the known recruitment of learning and memory centers in the brain has led investigators to hypothesize that the alterations in glutamatergic synaptic efficacy brought on by synaptic plasticity may play key roles in the addiction process. Here we review the present literature, examining the properties of synaptic plasticity within drug reward circuitry, and the effects that drugs of abuse have on these forms of plasticity. Interestingly, multiple forms of synaptic plasticity can be induced at glutamatergic synapses within the dorsal striatum, its ventral extension the nucleus accumbens, and the ventral tegmental area, and at least some of these forms of plasticity are regulated by behaviorally meaningful administration of cocaine and/or amphetamine. Thus, the present data suggest that regulation of synaptic plasticity in reward circuits is a tractable candidate mechanism underlying aspects of addiction.

75 FR 79383 - Unapproved Animal Drugs

Science.gov (United States)

2010-12-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0528] Unapproved Animal Drugs AGENCY: Food and Drug Administration, HHS. ACTION: Notice; request for comments. SUMMARY: The Food and Drug Administration (FDA, the Agency) is soliciting comments from stakeholders on...

Zolpidem prescribing practices before and after Food and Drug Administration required product labeling changes

OpenAIRE

Norman, Jessica L; Fixen, Danielle R; Saseen, Joseph J; Saba, Laura M; Linnebur, Sunny A

2017-01-01

Background: Women have higher morning serum zolpidem concentrations than men after taking an evening dose, potentially leading to increased risk of harm. On 19 April 2013, the United States Food and Drug Administration required labeling changes for zolpidem, recommending an initial dose of no greater than 5 mg (immediate release) or 6.25 mg (controlled release) per night in women. Objectives: The primary objective of this study was to compare prescribing practices before and after the 2013 zo...

77 FR 8262 - Draft Guidance on Investigational New Drug Applications for Positron Emission Tomography Drugs...

Science.gov (United States)

2012-02-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0081] Draft Guidance on Investigational New Drug Applications for Positron Emission Tomography Drugs; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...

Predicting abuse potential of stimulants and other dopaminergic drugs: overview and recommendations.

Science.gov (United States)

Huskinson, Sally L; Naylor, Jennifer E; Rowlett, James K; Freeman, Kevin B

2014-12-01

Examination of a drug's abuse potential at multiple levels of analysis (molecular/cellular action, whole-organism behavior, epidemiological data) is an essential component to regulating controlled substances under the Controlled Substances Act (CSA). We reviewed studies that examined several central nervous system (CNS) stimulants, focusing on those with primarily dopaminergic actions, in drug self-administration, drug discrimination, and physical dependence. For drug self-administration and drug discrimination, we distinguished between experiments conducted with rats and nonhuman primates (NHP) to highlight the common and unique attributes of each model in the assessment of abuse potential. Our review of drug self-administration studies suggests that this procedure is important in predicting abuse potential of dopaminergic compounds, but there were many false positives. We recommended that tests to determine how reinforcing a drug is relative to a known drug of abuse may be more predictive of abuse potential than tests that yield a binary, yes-or-no classification. Several false positives also occurred with drug discrimination. With this procedure, we recommended that future research follow a standard decision-tree approach that may require examining the drug being tested for abuse potential as the training stimulus. This approach would also allow several known drugs of abuse to be tested for substitution, and this may reduce false positives. Finally, we reviewed evidence of physical dependence with stimulants and discussed the feasibility of modeling these phenomena in nonhuman animals in a rational and practical fashion. This article is part of the Special Issue entitled 'CNS Stimulants'. Copyright © 2014 Elsevier Ltd. All rights reserved.

Multiple polysaccharide-drug complex-loaded liposomes: A unique strategy in drug loading and cancer targeting.

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Ruttala, Hima Bindu; Ramasamy, Thiruganesh; Gupta, Biki; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2017-10-01

In the present study, a unique strategy was developed to develop nanocarriers containing multiple therapeutics with controlled release characteristics. In this study, we demonstrated the synthesis of dextran sulfate-doxorubicin (DS-DOX) and alginate-cisplatin (AL-CIS) polymer-drug complexes to produce a transferrin ligand-conjugated liposome. The targeted nanoparticles (TL-DDAC) were nano-sized and spherical. The targeted liposome exhibited a specific receptor-mediated endocytic uptake in cancer cells. The enhanced cellular uptake of TL-DDAC resulted in a significantly better anticancer effect in resistant and sensitive breast cancer cells compared to that of the free drugs. Specifically, DOX and CIS at a molar ratio of 1:1 exhibited better therapeutic performance compared to that of other combinations. The combination of an anthracycline-based topoisomerase II inhibitor (DOX) and a platinum compound (CIS) resulted in significantly higher cell apoptosis (early and late) in both types of cancer cells. In conclusion, treatment with DS-DOX and AL-CIS based combination liposomes modified with transferrin (TL-DDAC) was an effective cancer treatment strategy. Further investigation in clinically relevant animal models is warranted to prove the therapeutic efficacy of this unique strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Logic for Inclusion of Administrative Domains and Administrators in Multi-domain Authorization

Science.gov (United States)

Iranmanesh, Zeinab; Amini, Morteza; Jalili, Rasool

Authorization policies for an administrative domain or a composition of multiple domains in multi-domain environments are determined by either one administrator or multiple administrators' cooperation. Several logic-based models for multi-domain environments' authorization have been proposed; however, they have not considered administrators and administrative domains in policies' representation. In this paper, we propose the syntax, proof theory, and semantics of a logic for multi-domain authorization policies including administrators and administrative domains. Considering administrators in policies provides the possibility of presenting composite administration having applicability in many collaborative applications. Indeed, administrators and administrative domains stated in policies can be used in authorization. The presented logic is based on modal logic and utilizes two calculi named the calculus of administrative domains and the calculus of administrators. It is also proved that the logic is sound. A case study is presented signifying the logic application in practical projects.

21 CFR 880.5440 - Intravascular administration set.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Intravascular administration set. 880.5440 Section 880.5440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL HOSPITAL AND PERSONAL USE DEVICES General Hospital and Personal Use...

Significance of MDR1 and multiple drug resistance in refractory human epileptic brain

Directory of Open Access Journals (Sweden)

Dini Gabriele

2004-10-01

Full Text Available Abstract Background The multiple drug resistance protein (MDR1/P-glycoprotein is overexpressed in glia and blood-brain barrier (BBB endothelium in drug refractory human epileptic tissue. Since various antiepileptic drugs (AEDs can act as substrates for MDR1, the enhanced expression/function of this protein may increase their active extrusion from the brain, resulting in decreased responsiveness to AEDs. Methods Human drug resistant epileptic brain tissues were collected after surgical resection. Astrocyte cell cultures were established from these tissues, and commercially available normal human astrocytes were used as controls. Uptake of fluorescent doxorubicin and radioactive-labeled Phenytoin was measured in the two cell populations, and the effect of MDR1 blockers was evaluated. Frozen human epileptic brain tissue slices were double immunostained to locate MDR1 in neurons and glia. Other slices were exposed to toxic concentrations of Phenytoin to study cell viability in the presence or absence of a specific MDR1 blocker. Results MDR1 was overexpressed in blood vessels, astrocytes and neurons in human epileptic drug-resistant brain. In addition, MDR1-mediated cellular drug extrusion was increased in human 'epileptic' astrocytes compared to 'normal' ones. Concomitantly, cell viability in the presence of cytotoxic compounds was increased. Conclusions Overexpression of MDR1 in different cell types in drug-resistant epileptic human brain leads to functional alterations, not all of which are linked to drug pharmacokinetics. In particular, the modulation of glioneuronal MDR1 function in epileptic brain in the presence of toxic concentrations of xenobiotics may constitute a novel cytoprotective mechanism.

Adverse event management in mass drug administration for neglected tropical diseases.

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Caplan, Arthur; Zink, Amanda

2014-03-01

The ethical challenges of reporting and managing adverse events (AEs) and serious AEs (SAEs) in the context of mass drug administration (MDA) for the treatment of neglected tropical diseases (NTDs) require reassessment of domestic and international policies on a global scale. Although the World Health Organization has set forth AE/SAE guidelines specifically for NTD MDA that incorporate suspected causality, and recommends that only SAEs get reported in this setting, most regulatory agencies continue to require the reporting of all SAEs exhibiting even a merely temporal relationship to activities associated with an MDA program. This greatly increases the potential for excess "noise" and undue risk aversion and is not only impractical but arguably unethical where huge proportions of populations are being treated for devastating diseases, and no good baseline exists against which to compare possible AE/SAE reports. Other population-specific variables that might change the way drug safety ought to be assessed include differing efficacy rates of a drug, background morbidity/mortality rates of the target disease in question, the growth rate of the incidence of disease, the availability of rescue or salvage therapies, and the willingness of local populations to take risks that other populations might not. The fact that NTDs are controllable and potentially eradicable with well-tolerated, effective, existing drugs might further alter our assessment of MDA safety and AE/SAE tolerability. At the same time, diffuseness of population, communication barriers, lack of resources, and other difficult surveillance challenges may present in NTD-affected settings. These limitations could impair the ability to monitor an MDA program's success, as well as hinder efforts to obtain informed consent or provide rescue therapy. Denying beneficial research interventions and MDA programs intended to benefit millions requires sound ethical justification based on more than the identification of

Clinical relevance of cimetidine drug interactions.

Science.gov (United States)

Shinn, A F

1992-01-01

The excellent efficacy and tolerability profiles of H2-antagonists have established these agents as the leading class of antiulcer drugs. Attention has been focused on drug interactions with H2-antagonists as a means of product differentiation and because many patients are receiving multiple drug therapy. The main mechanism of most drug interactions involving cimetidine appears to be inhibition of the hepatic microsomal enzyme cytochrome P450, an effect which may be related to the different structures of H2-antagonists. Ranitidine appears to have less affinity than cimetidine for this system. There have been many published case reports and studies of drug interactions with cimetidine, but many of these have provided pharmacokinetic data only, with little information concerning the clinical significance of these findings. Nevertheless, the coadministration of cimetidine with drugs that have a narrow therapeutic margin (such as theophylline) may potentially result in clinically significant adverse effects. The monitoring of serum concentrations of drugs coadministered with cimetidine may reduce the risk of adverse events but does not abolish the problem. However, for most patients, concomitant administration of cimetidine with drugs possessing a wide therapeutic margin is unlikely to pose a significant problem.

Dendrimer-magnetic nanoparticles as multiple stimuli responsive and enzymatic drug delivery vehicle

International Nuclear Information System (INIS)

Chandra, Sudeshna; Noronha, Glen; Dietrich, Sascha; Lang, Heinrich; Bahadur, Dhirendra

2015-01-01

Two different chain lengths of (poly)ethylene glycol-PAMAM dendrimers namely, L6-PEG-PAMAM and S6-PEG-PAMAM with six end-grafted ethylene glycol ether-tentacles of type CH 2 CH 2 C(O)O(CH 2 CH 2 O) 9 CH 3 and CH 2 CH 2 C(O)O(CH 2 CH 2 O) 2 C 2 H 5 , respectively, were synthesized. These dendrimers have multiple σ-donor capabilities and therefore, were used for stabilizing the magnetite (Fe 3 O 4 ) nanoparticles. Both the dendrimer-magnetic nanoparticles (L6-PEG-PAMAM-MNPs and S6-PEG-PAMAM-MNPs) were characterized by different spectroscopic and microstructural techniques. The nanoparticles were mesoporous and superparamagnetic and therefore, explored for their possible use in delivery of cancer drug, doxorubicin (DOX). In the developed drug delivery system, achieving high drug-loading efficiency with controllable release were the main challenges. The change in zeta potential and quenching of fluorescence intensity suggests chemical interaction between DOX and the nanoparticles. The loading efficiency was calculated to be over 95% with a sustained pH and temperature sensitive release. Further, enzyme cathepsin B has also been used to degrade the dendritic shell to trigger sustained drug release in the vicinity of tumor cells

A systematic review of factors that shape implementation of mass drug administration for lymphatic filariasis in sub-Saharan Africa.

Science.gov (United States)

Silumbwe, Adam; Zulu, Joseph Mumba; Halwindi, Hikabasa; Jacobs, Choolwe; Zgambo, Jessy; Dambe, Rosalia; Chola, Mumbi; Chongwe, Gershom; Michelo, Charles

2017-05-22

Understanding factors surrounding the implementation process of mass drug administration for lymphatic filariasis (MDA for LF) elimination programmes is critical for successful implementation of similar interventions. The sub-Saharan Africa (SSA) region records the second highest prevalence of the disease and subsequently several countries have initiated and implemented MDA for LF. Systematic reviews have largely focused on factors that affect coverage and compliance, with less attention on the implementation of MDA for LF activities. This review therefore seeks to document facilitators and barriers to implementation of MDA for LF in sub-Saharan Africa. A systematic search of databases PubMed, Science Direct and Google Scholar was conducted. English peer-reviewed publications focusing on implementation of MDA for LF from 2000 to 2016 were considered for analysis. Using thematic analysis, we synthesized the final 18 articles to identify key facilitators and barriers to MDA for LF programme implementation. The main factors facilitating implementation of MDA for LF programmes were awareness creation through innovative community health education programmes, creation of partnerships and collaborations, integration with existing programmes, creation of morbidity management programmes, motivation of community drug distributors (CDDs) through incentives and training, and management of adverse effects. Barriers to implementation included the lack of geographical demarcations and unregistered migrations into rapidly urbanizing areas, major disease outbreaks like the Ebola virus disease in West Africa, delayed drug deliveries at both country and community levels, inappropriate drug delivery strategies, limited number of drug distributors and the large number of households allocated for drug distribution. Mass drug administration for lymphatic filariasis elimination programmes should design their implementation strategies differently based on specific contextual factors to

A systematic review of factors that shape implementation of mass drug administration for lymphatic filariasis in sub-Saharan Africa

Directory of Open Access Journals (Sweden)

Adam Silumbwe

2017-05-01

Full Text Available Abstract Background Understanding factors surrounding the implementation process of mass drug administration for lymphatic filariasis (MDA for LF elimination programmes is critical for successful implementation of similar interventions. The sub-Saharan Africa (SSA region records the second highest prevalence of the disease and subsequently several countries have initiated and implemented MDA for LF. Systematic reviews have largely focused on factors that affect coverage and compliance, with less attention on the implementation of MDA for LF activities. This review therefore seeks to document facilitators and barriers to implementation of MDA for LF in sub-Saharan Africa. Methods A systematic search of databases PubMed, Science Direct and Google Scholar was conducted. English peer-reviewed publications focusing on implementation of MDA for LF from 2000 to 2016 were considered for analysis. Using thematic analysis, we synthesized the final 18 articles to identify key facilitators and barriers to MDA for LF programme implementation. Results The main factors facilitating implementation of MDA for LF programmes were awareness creation through innovative community health education programmes, creation of partnerships and collaborations, integration with existing programmes, creation of morbidity management programmes, motivation of community drug distributors (CDDs through incentives and training, and management of adverse effects. Barriers to implementation included the lack of geographical demarcations and unregistered migrations into rapidly urbanizing areas, major disease outbreaks like the Ebola virus disease in West Africa, delayed drug deliveries at both country and community levels, inappropriate drug delivery strategies, limited number of drug distributors and the large number of households allocated for drug distribution. Conclusion Mass drug administration for lymphatic filariasis elimination programmes should design their implementation

New and emerging immune-targeted drugs for the treatment of multiple sclerosis.

Science.gov (United States)

Palmer, Alan M

2014-07-01

Multiple sclerosis (MS) is a neurodegenerative disease with a major inflammatory component that constitutes the most common progressive and disabling neurological condition in young adults. Injectable immunomodulatory medicines such as interferon drugs and glatiramer acetate have dominated the MS market for over the past two decades but this situation is set to change. This is because of: (i) patent expirations, (ii) the introduction of natalizumab, which targets the interaction between leukocytes and the blood-CNS barrier, (iii) the launch of three oral immunomodulatory drugs (fingolimod, dimethyl fumarate and teriflunomide), with another (laquinimod) under regulatory review and (iv) a number of immunomodulatory monoclonal antibodies (alemtuzumab, daclizumab and ocrelizumab) about to enter the market. Current and emerging medicines are reviewed and their impact on people with MS considered. © 2013 The British Pharmacological Society.

Concurrent administration of anticancer chemotherapy drug and herbal medicine on the perspective of pharmacokinetics

Directory of Open Access Journals (Sweden)

Yung-Yi Cheng

2018-04-01

Full Text Available With an increasing number of cancer patients seeking an improved quality of life, complementary and alternative therapies are becoming more common ways to achieve such improvements. The potential risks of concurrent administration are serious and must be addressed. However, comprehensive evidence for the risks and benefits of combining anticancer drugs with traditional herbs is rare. Pharmacokinetic investigations are an efficient way to understand the influence of concomitant remedies. Therefore, this study aimed to collect the results of pharmacokinetic studies relating to the concurrent use of cancer chemotherapy and complementary and alternative therapies. According to the National Health Insurance (NHI database in Taiwan and several publications, the three most commonly prescribed formulations for cancer patients are Xiang-Sha-Liu-Jun-Zi-Tang, Jia-Wei-Xiao-Yao-San and Bu-Zhong-Yi-Qi-Tang. The three most commonly prescribed single herbs for cancer patients are Hedyotis diffusa, Scutellaria barbata, and Astragalus membranaceus. Few studies have discussed herb–drug interactions involving these herbs from a pharmacokinetics perspective. Here, we reviewed Jia-Wei-Xiao-Yao-San, Long-Dan-Xie-Gan-Tang, Curcuma longa and milk thistle to provide information based on pharmacokinetic evidence for healthcare professionals to use in educating patients about the risks of the concomitant use of various remedies. Keywords: Traditional Chinese medicine, Chemotherapy drug, Pharmacokinetics, Herb–drug interaction

75 FR 81455 - New Animal Drugs; Deslorelin

Science.gov (United States)

2010-12-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510 and 522 [Docket No. FDA-2010-N-0002] New Animal Drugs; Deslorelin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

75 FR 1275 - New Animal Drugs; Ractopamine

Science.gov (United States)

2010-01-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 558 [Docket No. FDA-2009-N-0665] New Animal Drugs; Ractopamine AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to...

Food and Drug Administration warning on anesthesia and brain development: implications for obstetric and fetal surgery.

Science.gov (United States)

Olutoye, Olutoyin A; Baker, Byron Wycke; Belfort, Michael A; Olutoye, Oluyinka O

2018-01-01

There has been growing concern about the detrimental effects of certain anesthetic agents on the developing brain. Preclinical studies in small animal models as well as nonhuman primates suggested loss or death of brain cells and consequent impaired neurocognitive function following anesthetic exposure in neonates and late gestation fetuses. Human studies in this area are limited and currently inconclusive. On Dec. 14, 2016, the US Food and Drug Administration issued a warning regarding impaired brain development in children following exposure to certain anesthetic agents used for general anesthesia, namely the inhalational anesthetics isoflurane, sevoflurane, and desflurane, and the intravenous agents propofol and midazolam, in the third trimester of pregnancy. Furthermore, this warning recommends that health care professionals should balance the benefits of appropriate anesthesia in young children and pregnant women against potential risks, especially for procedures that may last >3 hours or if multiple procedures are required in children surgery in the second and third trimester; this exposure is typically longer than that for cesarean delivery. Very few studies address the effect of anesthetic exposure on the fetus in the second trimester when most nonobstetric and fetal surgical procedures are performed. It is also unclear how the plasticity of the fetal brain at this stage of development will modulate the consequences of anesthetic exposure. Strategies that may circumvent possible untoward long-term neurologic effects of anesthesia in the baby include: (1) use of nonimplicated (nongamma-aminobutyric acid agonist) agents for sedation such as opioids (remifentanil, fentanyl) or the alpha-2 agonist, dexmedetomidine, when appropriate; (2) minimizing the duration of exposure to inhalational anesthetics for fetal, obstetric, and nonobstetric procedures in the pregnant patient, as much as possible within safe limits; and (3) commencing surgery promptly and limiting

75 FR 60767 - Office of the Commissioner; Request for Comments on the Food and Drug Administration Fiscal Year...

Science.gov (United States)

2010-10-01

... Science and Innovation, (2) Strengthen the Safety and Integrity of the Global Supply Chain, (3) Strengthen... comments to the Division of Dockets Management (HFA- 305), Food and Drug Administration, 5630 Fishers Lane... strengthen the strategic management structure currently in place. For comparison purposes, the current FDA...

Controlling prescription drug costs: regulation and the role of interest groups in Medicare and the Veterans Health Administration.

Science.gov (United States)

Frakt, Austin B; Pizer, Steven D; Hendricks, Ann M

2008-12-01

Medicare and the Veterans Health Administration (VA) both finance large outpatient prescription drug programs, though in very different ways. In the ongoing debate on how to control Medicare spending, some suggest that Medicare should negotiate directly with drug manufacturers, as the VA does. In this article we relate the role of interest groups to policy differences between Medicare and the VA and, in doing so, explain why such a large change to the Medicare drug program is unlikely. We argue that key policy differences are attributable to stable differences in interest group involvement. While this stability makes major changes in Medicare unlikely, it suggests the possibility of leveraging VA drug purchasing to achieve savings in Medicare. This could be done through a VA-administered drug-only benefit for Medicare-enrolled veterans. Such a partnership could incorporate key elements of both programs: capacity to accept large numbers of enrollees (like Medicare) and leverage to negotiate prescription drug prices (like the VA). Moreover, it could be implemented at no cost to the VA while achieving savings for Medicare and beneficiaries.

Influence of route of administration/drug formulation and other factors on adherence to treatment in rheumatoid arthritis (pain related) and dyslipidemia (non-pain related).

Science.gov (United States)

Fautrel, Bruno; Balsa, Alejandro; Van Riel, Piet; Casillas, Marta; Capron, Jean-Philippe; Cueille, Carine; de la Torre, Inmaculada

2017-07-01

A comprehensive review was performed to investigate the effect of route of administration on medication adherence and persistence in rheumatoid arthritis (RA) and to compare adherence/persistence with oral medications between RA and a non-painful disease (dyslipidemia). Comprehensive database searches were performed to identify studies investigating medication adherence and/or persistence in adults with RA receiving conventional synthetic or biologic agents. Similar searches were performed for studies of patients with dyslipidemia receiving statins. Studies had to be published after 1998 in English and involve ≥6 months' follow up. Adherence and persistence were compared between the different routes of drug administration in RA, and between the two diseases for oral medications. A total of 35 and 28 papers underwent data extraction for RA and dyslipidemia, respectively. Within the constraints of the analysis, adherence and persistence rates appeared broadly similar for the different routes of drug administration in RA. Adherence to oral medications was also broadly similar across the two diseases, but persistence was lower in dyslipidemia. Poor adherence has clinical consequences in both diseases: greater disease activity and risk of flare in RA, and increased serum cholesterol levels and risk of heart and cerebrovascular disease in dyslipidemia. Over 1-3 years, poor adherence to biologic RA medications led to increased resource use and medical costs but lower total direct costs due to reduced biologic drug costs. Conversely, poor adherence to dyslipidemia medications resulted in increased total direct costs. In both diseases, adherence improved with patient education/support. The route of drug administration and the symptomatic (pain) nature of the disease do not appear to be dominant factors for drug adherence or persistence in RA. The wide range of adherence and persistence values and definitions across studies made comparisons between drug formulations and

76 FR 6326 - New Animal Drugs; Masitinib

Science.gov (United States)

2011-02-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510 and 516 [Docket No. FDA-2011-N-0003] New Animal Drugs; Masitinib AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to...

75 FR 79295 - New Animal Drugs; Mupirocin

Science.gov (United States)

2010-12-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510 and 524 [Docket No. FDA-2010-N-0002] New Animal Drugs; Mupirocin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to...

Anti-Obesity Agents and the US Food and Drug Administration.

Science.gov (United States)

Casey, Martin F; Mechanick, Jeffrey I

2014-09-01

Despite the growing market for obesity care, the US Food and Drug Administration (FDA) has approved only two new pharmaceutical agents-lorcaserin and combination phentermine/topiramate-for weight reduction since 2000, while removing three agents from the market in the same time period. This article explores the FDA's history and role in the approval of anti-obesity medications within the context of a public health model of obesity. Through the review of obesity literature and FDA approval documents, we identified two major barriers preventing fair evaluation of anti-obesity agents including: (1) methodological pitfalls in clinical trials and (2) misaligned values in the assessment of anti-obesity agents. Specific recommendations include the use of adaptive (Bayesian) design protocols, value-based analyses of risks and benefits, and regulatory guidance based on a comprehensive, multi-platform obesity disease model. Positively addressing barriers in the FDA approval process of anti-obesity agents may have many beneficial effects within an obesity disease model.

Pharmacokinetics and selected pharmacodynamics of trazodone following intravenous and oral administration to horses undergoing fitness training.

Science.gov (United States)

Knych, Heather K; Mama, Khursheed R; Steffey, Eugene P; Stanley, Scott D; Kass, Philip H

2017-10-01

OBJECTIVE To measure concentrations of trazodone and its major metabolite in plasma and urine after administration to healthy horses and concurrently assess selected physiologic and behavioral effects of the drug. ANIMALS 11 Thoroughbred horses enrolled in a fitness training program. PROCEDURES In a pilot investigation, 4 horses received trazodone IV (n = 2) or orally (2) to select a dose for the full study; 1 horse received a vehicle control treatment IV. For the full study, trazodone was initially administered IV (1.5 mg/kg) to 6 horses and subsequently given orally (4 mg/kg), with a 5-week washout period between treatments. Blood and urine samples were collected prior to drug administration and at multiple time points up to 48 hours afterward. Samples were analyzed for trazodone and metabolite concentrations, and pharmacokinetic parameters were determined; plasma drug concentrations following IV administration best fit a 3-compartment model. Behavioral and physiologic effects were assessed. RESULTS After IV administration, total clearance of trazodone was 6.85 ± 2.80 mL/min/kg, volume of distribution at steady state was 1.06 ± 0.07 L/kg, and elimination half-life was 8.58 ± 1.88 hours. Terminal phase half-life was 7.11 ± 1.70 hours after oral administration. Horses had signs of aggression and excitation, tremors, and ataxia at the highest IV dose (2 mg/kg) in the pilot investigation. After IV drug administration in the full study (1.5 mg/kg), horses were ataxic and had tremors; sedation was evident after oral administration. CONCLUSIONS AND CLINICAL RELEVANCE Administration of trazodone to horses elicited a wide range of effects. Additional study is warranted before clinical use of trazodone in horses can be recommended.

Health-Related Quality of Life in Patients with Multiple Sclerosis : Impact of Disease-Modifying Drugs

NARCIS (Netherlands)

Jongen, Peter Joseph

Multiple sclerosis (MS) has a profound impact on health-related quality of life (HRQoL), a comprehensive subjective measure of the patient's health status. Assessment of HRQoL informs on the potential advantages and disadvantages of disease-modifying drugs (DMDs) beyond their effects on

"Who has ever loved a drug addict? It's a lie. They think a 'teja' is as bad person": multiple stigmas faced by women who inject drugs in coastal Kenya.

Science.gov (United States)

Mburu, Gitau; Ayon, Sylvia; Tsai, Alexander C; Ndimbii, James; Wang, Bangyuan; Strathdee, Steffanie; Seeley, Janet

2018-05-25

A tenth of all people who inject drugs in Kenya are women, yet their social contexts and experiences remain poorly understood. This paper reports how multiple forms of stigma are experienced by women who inject drugs in coastal Kenya and the impact that they have on their ability to access essential health services. In 2015, in-depth interviews and focus group discussions were held with 45 women who inject drugs in two coastal towns. These data were supplemented with in-depth interviews with five individual stakeholders involved in service provision to this population. Data were analyzed thematically using NVivo. Women who inject drugs experience multiple stigmas, often simultaneously. These included the external stigma and self-stigma of injection drug use, external gender-related stigma of being a female injecting drug user, and the external stigma of being HIV positive (i.e., among those living with HIV). Stigma led to rejection, social exclusion, low self-esteem, and delay or denial of services at health facilities. HIV and harm reduction programs should incorporate interventions that address different forms of stigma among women who inject drugs in coastal Kenya. Addressing stigma will require a combination of individual, social, and structural interventions, such as collective empowerment of injecting drug users, training of healthcare providers on issues and needs of women who inject drugs, peer accompaniment to health facilities, addressing wider social determinants of stigma and discrimination, and expansion of harm reduction interventions to change perceptions of communities towards women who inject drugs.

Multiple Input - Multiple Output (MIMO) SAR

Data.gov (United States)

National Aeronautics and Space Administration — This effort will research and implement advanced Multiple-Input Multiple-Output (MIMO) Synthetic Aperture Radar (SAR) techniques which have the potential to improve...

Dendrimer-magnetic nanoparticles as multiple stimuli responsive and enzymatic drug delivery vehicle

Energy Technology Data Exchange (ETDEWEB)

Chandra, Sudeshna; Noronha, Glen [Metallurgical and Materials Science Department, Indian Institute of Technology Bombay, Powai, Mumbai, 400076 (India); Dietrich, Sascha; Lang, Heinrich [Technische Universität Chemnitz, Institute of Chemistry, Straße der Nationen 62, d-09111 Chemnitz (Germany); Bahadur, Dhirendra, E-mail: dhirenb@iitb.ac.in [Metallurgical and Materials Science Department, Indian Institute of Technology Bombay, Powai, Mumbai, 400076 (India)

2015-04-15

Two different chain lengths of (poly)ethylene glycol-PAMAM dendrimers namely, L6-PEG-PAMAM and S6-PEG-PAMAM with six end-grafted ethylene glycol ether-tentacles of type CH{sub 2}CH{sub 2}C(O)O(CH{sub 2}CH{sub 2}O){sub 9}CH{sub 3} and CH{sub 2}CH{sub 2}C(O)O(CH{sub 2}CH{sub 2}O){sub 2}C{sub 2}H{sub 5}, respectively, were synthesized. These dendrimers have multiple σ-donor capabilities and therefore, were used for stabilizing the magnetite (Fe{sub 3}O{sub 4}) nanoparticles. Both the dendrimer-magnetic nanoparticles (L6-PEG-PAMAM-MNPs and S6-PEG-PAMAM-MNPs) were characterized by different spectroscopic and microstructural techniques. The nanoparticles were mesoporous and superparamagnetic and therefore, explored for their possible use in delivery of cancer drug, doxorubicin (DOX). In the developed drug delivery system, achieving high drug-loading efficiency with controllable release were the main challenges. The change in zeta potential and quenching of fluorescence intensity suggests chemical interaction between DOX and the nanoparticles. The loading efficiency was calculated to be over 95% with a sustained pH and temperature sensitive release. Further, enzyme cathepsin B has also been used to degrade the dendritic shell to trigger sustained drug release in the vicinity of tumor cells.

Circumvention of Mcl-1-dependent drug resistance by simultaneous Chk1 and MEK1/2 inhibition in human multiple myeloma cells.

Science.gov (United States)

Pei, Xin-Yan; Dai, Yun; Felthousen, Jessica; Chen, Shuang; Takabatake, Yukie; Zhou, Liang; Youssefian, Leena E; Sanderson, Michael W; Bodie, Wesley W; Kramer, Lora B; Orlowski, Robert Z; Grant, Steven

2014-01-01

The anti-apoptotic protein Mcl-1 plays a major role in multiple myeloma (MM) cell survival as well as bortezomib- and microenvironmental forms of drug resistance in this disease. Consequently, there is a critical need for strategies capable of targeting Mcl-1-dependent drug resistance in MM. The present results indicate that a regimen combining Chk1 with MEK1/2 inhibitors effectively kills cells displaying multiple forms of drug resistance stemming from Mcl-1 up-regulation in association with direct transcriptional Mcl-1 down-regulation and indirect disabling of Mcl-1 anti-apoptotic function through Bim up-regulation and increased Bim/Mcl-1 binding. These actions release Bak from Mcl-1, accompanied by Bak/Bax activation. Analogous events were observed in both drug-naïve and acquired bortezomib-resistant MM cells displaying increased Mcl-1 but diminished Bim expression, or cells ectopically expressing Mcl-1. Moreover, concomitant Chk1 and MEK1/2 inhibition blocked Mcl-1 up-regulation induced by IL-6/IGF-1 or co-culture with stromal cells, effectively overcoming microenvironment-related drug resistance. Finally, this regimen down-regulated Mcl-1 and robustly killed primary CD138+ MM cells, but not normal hematopoietic cells. Together, these findings provide novel evidence that this targeted combination strategy could be effective in the setting of multiple forms of Mcl-1-related drug resistance in MM.

Circumvention of Mcl-1-dependent drug resistance by simultaneous Chk1 and MEK1/2 inhibition in human multiple myeloma cells.

Directory of Open Access Journals (Sweden)

Xin-Yan Pei

Full Text Available The anti-apoptotic protein Mcl-1 plays a major role in multiple myeloma (MM cell survival as well as bortezomib- and microenvironmental forms of drug resistance in this disease. Consequently, there is a critical need for strategies capable of targeting Mcl-1-dependent drug resistance in MM. The present results indicate that a regimen combining Chk1 with MEK1/2 inhibitors effectively kills cells displaying multiple forms of drug resistance stemming from Mcl-1 up-regulation in association with direct transcriptional Mcl-1 down-regulation and indirect disabling of Mcl-1 anti-apoptotic function through Bim up-regulation and increased Bim/Mcl-1 binding. These actions release Bak from Mcl-1, accompanied by Bak/Bax activation. Analogous events were observed in both drug-naïve and acquired bortezomib-resistant MM cells displaying increased Mcl-1 but diminished Bim expression, or cells ectopically expressing Mcl-1. Moreover, concomitant Chk1 and MEK1/2 inhibition blocked Mcl-1 up-regulation induced by IL-6/IGF-1 or co-culture with stromal cells, effectively overcoming microenvironment-related drug resistance. Finally, this regimen down-regulated Mcl-1 and robustly killed primary CD138+ MM cells, but not normal hematopoietic cells. Together, these findings provide novel evidence that this targeted combination strategy could be effective in the setting of multiple forms of Mcl-1-related drug resistance in MM.

Protein kinase C isozymes as regulators of sensitivity to and self-administration of drugs of abuse-studies with genetically modified mice.

Science.gov (United States)

Olive, Michael Foster; Newton, Philip M

2010-09-01

Studies using targeted gene deletion in mice have revealed distinct roles for individual isozymes of the protein kinase C (PKC) family of enzymes in regulating sensitivity to various drugs of abuse. These changes in drug sensitivity are associated with altered patterns of drug self-administration. The purpose of this review is to summarize behavioral studies conducted on mice carrying targeted deletions of genes encoding specific PKC isozymes (namely the beta, gamma, delta, and epsilon isozymes), and to critically evaluate the possibility of using pharmacological inhibitors of specific PKC isozymes as modulators of the sensitivity to various drugs of abuse, as well as potential aids in the treatment of substance use disorders.

Drug-Induced Liver Injury by Glatiramer Acetate Used for Treatment of Multiple Sclerosis

Directory of Open Access Journals (Sweden)

Attila Onmez

2013-12-01

Full Text Available Glatiramer acetate (GA, Copaxone is an approved drug for the treatment of relapsing–remitting multiple sclerosis. Most common side effects observed with GA are local injection site reactions, which can include pain, swelling, or redness. However, systemic adverse event such as hepatotoxicity related to GA is rarely seen. In this report, we present a case of GA-induced toxic hepatitis associated with cholestatic and hepatocellular damage.

The Development of Multiple Intelligence Capabilities for Early Childhood Development Center, Local Administration Organization in Chaiyaphum Province

Science.gov (United States)

Siphai, Sunan; Supandee, Terdsak; Raksapuk, Chunpit; Poopayang, Piangkhae; Kratoorerk, Sangsan

2017-01-01

The aim of this research is to promote multiple intelligence capabilities for Early Childhood Care Center of a Sub-district Administration Organization in Chaiyaphum Province. The sample applied were 61 children aging between 3 and 5 years old at Child Development Center, Tambon Ban Kok, Amphoe Chaturus, Chaiyaphum Province, who were selected…

Local drug delivery - the early Berlin experience: single drug administration versus sustained release.

Science.gov (United States)

Speck, Ulrich; Scheller, Bruno; Rutsch, Wolfgang; Laule, Michael; Stangl, Verena

2011-05-01

Our initial investigations into restenosis inhibition by local drug delivery were prompted by reports on an improved outcome of coronary interventions, including a lower rate of target lesion revascularisation, when the intervention was performed with an ionic instead of non-ionic contrast medium. Although this was not confirmed in an animal study, the short exposure of the vessel wall to paclitaxel dissolved in contrast agent or coated on balloons proved to be efficacious. A study comparing three methods of local drug delivery to the coronary artery in pigs indicated the following order of efficacy in inhibiting neointimal proliferation: paclitaxel-coated balloons > sirolimus-eluting stents, sustained drug release > paclitaxel in contrast medium. Cell culture experiments confirmed that cell proliferation can be inhibited by very short exposure to the drug. Shorter exposure times require higher drug concentrations. Effective paclitaxel concentrations in porcine arteries are achieved when the drug is dissolved in contrast medium or coated on balloons. Paclitaxel is an exceptional drug in that it stays in the treated tissue for a long time. This may explain the long-lasting efficacy of paclitaxel-coated balloons, but does not disprove the hypothesis that the agent blocks a process initiating long-lasting excessive neointimal proliferation, which occurs early after vessel injury.

Fertility, pregnancy and childbirth in patients with multiple sclerosis: impact of disease-modifying drugs.

Science.gov (United States)

Amato, Maria Pia; Portaccio, Emilio

2015-03-01

In recent decades, pregnancy-related issues in multiple sclerosis (MS) have received growing interest. MS is more frequent in women than in men and typically starts during child-bearing age. An increasing number of disease-modifying drugs (DMDs) for the treatment of MS are becoming available. Gathering information on their influences on pregnancy-related issues is of crucial importance for the counselling of MS patients. As for the immunomodulatory drugs (interferons and glatiramer acetate), accumulating evidence points to the relative safety of pregnancy exposure in terms of maternal and foetal outcomes. In case of higher clinical disease activity before pregnancy, these drugs could be continued until conception. As for the 'newer' drugs (fingolimod, natalizumab, teriflunomide, dimethyl fumarate and alemtuzumab), the information is more limited. Whereas fingolimod and teriflunomide are likely associated with an increased risk of foetal malformations, the effects of natalizumab, dimethyl fumarate and alemtuzumab still need to be ascertained. This article provides a review of the available information on the use of DMDs during pregnancy, with a specific focus on fertility, foetal development, delivery and breast-feeding.

77 FR 65198 - Generic Drug User Fee-Abbreviated New Drug Application, Prior Approval Supplement, and Drug...

Science.gov (United States)

2012-10-25

..., U.S. postal money order, or wire transfer. FDA has partnered with the U.S. Department of the... money order and make payable to the order of the Food and Drug Administration. Your payment can be mailed to: Food and Drug Administration, P.O. Box 979108, St. Louis, MO 63197-9000. If checks are to be...

Zolpidem prescribing practices before and after Food and Drug Administration required product labeling changes

Directory of Open Access Journals (Sweden)

Jessica L Norman

2017-05-01

Full Text Available Background: Women have higher morning serum zolpidem concentrations than men after taking an evening dose, potentially leading to increased risk of harm. On 19 April 2013, the United States Food and Drug Administration required labeling changes for zolpidem, recommending an initial dose of no greater than 5 mg (immediate release or 6.25 mg (controlled release per night in women. Objectives: The primary objective of this study was to compare prescribing practices before and after the 2013 zolpidem labeling change. A secondary objective was to evaluate serious adverse events potentially related to zolpidem. Methods: Electronic medical records of adults receiving care through the University of Colorado Health system were accessed for study inclusion if patients were provided a first-time prescription for zolpidem either prior to or after the Food and Drug Administration labeling change. Patients were randomly chosen from eight strata based on age, gender, and date of zolpidem initiation (before/after the labeling change. Demographic and zolpidem prescribing data were collected. Low-dose zolpidem was considered 5 mg (immediate release or 6.25 mg (controlled release daily or less. Documentation of potentially related serious adverse events within the patients’ records was also evaluated. Results: A total of 400 patients were included in the study. The overall percentage of patients prescribed low-dose zolpidem increased from 44% to 58% after the labeling change (p = 0.0020. In a pre-specified subgroup analysis, the percentage of patients prescribed low-dose zolpidem increased in all groups, including young men (38%–50%, p = 0.23, elderly men (34%–40%, p = 0.53, and elderly women (60%–74%, p = 0.14, but the change was only significant in young women (42%–70%, p = 0.0045. Conclusion: After Food and Drug Administration–mandated labeling changes for zolpidem in 2013, the percentage of overall patients in our health

Cocaine self-administration in social dyads using custom-built operant conditioning chambers.

Science.gov (United States)

Lacy, Ryan T; Strickland, Justin C; Smith, Mark A

2014-10-30

Traditionally, the analysis of intravenous drug self-administration is limited to conditions in which subjects are tested in isolation. This limits the translational appeal of these studies because drug use in humans often occurs in the presence of others. We used custom-built operant conditioning chambers that allowed social dyads visual, olfactory, auditory, and limited tactile contact while concurrently self-administering cocaine. Male rats were trained to respond according to a fixed interval schedule of reinforcement (with a limited hold) in order to determine if patterns of cocaine (0.75mg/kg/infusion) self-administration became more similar over time in social pairs. Cocaine self-administration was tested across five days according to a 10-min fixed interval schedule (with a 5-min limited hold). Quarter-life values (time at which 25% of responses were emitted per interval) were analyzed using intraclass correlations. The total number of reinforcers obtained did not vary across the five days of testing; however, quarter-life values became progressively more similar between individuals within the social dyads. Standard operant conditioning chambers are unable to assess responding in multiple animals due to their small size, the need to prevent subjects from responding on the lever of their partner, and the need to prevent infusion lines from entangling. By using custom-built social operant conditioning chambers, we assessed the effects of social contact on cocaine self-administration. Social operant conditioning chambers can be used as a preclinical method to examine social influences on drug self-administration under conditions that approximate human substance use. Copyright © 2014 Elsevier B.V. All rights reserved.

75 FR 24394 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of a New Animal Drug...

Science.gov (United States)

2010-05-05

... [Docket No. FDA-2010-N-0002] Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of a New Animal Drug Application; Buquinolate; Coumaphos AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations by...

Route of administration for illicit prescription opioids: a comparison of rural and urban drug users

Directory of Open Access Journals (Sweden)

Havens Jennifer R

2010-10-01

Full Text Available Abstract Background Nonmedical prescription opioid use has emerged as a major public health concern in recent years, particularly in rural Appalachia. Little is known about the routes of administration (ROA involved in nonmedical prescription opioid use among rural and urban drug users. The purpose of this study was to describe rural-urban differences in ROA for nonmedical prescription opioid use. Methods A purposive sample of 212 prescription drug users was recruited from a rural Appalachian county (n = 101 and a major metropolitan area (n = 111 in Kentucky. Consenting participants were given an interviewer-administered questionnaire examining sociodemographics, psychiatric disorders, and self-reported nonmedical use and ROA (swallowing, snorting, injecting for the following prescription drugs: buprenorphine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, OxyContin® and other oxycodone. Results Among urban participants, swallowing was the most common ROA, contrasting sharply with substance-specific variation in ROA among rural participants. Among rural participants, snorting was the most frequent ROA for hydrocodone, methadone, OxyContin®, and oxycodone, while injection was most common for hydromorphone and morphine. In age-, gender-, and race-adjusted analyses, rural participants had significantly higher odds of snorting hydrocodone, OxyContin®, and oxycodone than urban participants. Urban participants had significantly higher odds of swallowing hydrocodone and oxycodone than did rural participants. Notably, among rural participants, 67% of hydromorphone users and 63% of morphine users had injected the drugs. Conclusions Alternative ROA are common among rural drug users. This finding has implications for rural substance abuse treatment and harm reduction, in which interventions should incorporate methods to prevent and reduce route-specific health complications of drug use.

Frequency and Severity of Neutropenia Associated with Food and Drug Administration Approved and Compounded Formulations of Lomustine in Dogs with Cancer

OpenAIRE

Burton, J.H.; Stanley, S.D.; Knych, H.K.; Rodriguez, C.O.; Skorupski, K.A.; Rebhun, R.B.

2015-01-01

Background Compounded lomustine is used commonly in veterinary patients. However, the potential variability in these formulations is unknown and concern exists that compounded formulations of drugs may differ in potency from Food and Drug Administration (FDA)?approved products. Hypothesis/Objectives The initial objective of this study was to evaluate the frequency and severity of neutropenia in dogs treated with compounded or FDA?approved formulations of lomustine. Subsequent analyses aimed t...

Prevention of Intraabdominal Adhesions by Local and Systemic Administration of Immunosuppressive Drugs

Science.gov (United States)

Peker, Kemal; Inal, Abdullah; Sayar, Ilyas; Sahin, Murat; Gullu, Huriye; Inal, Duriye Gul; Isik, Arda

2013-01-01

Background: Intraperitoneal adhesion formation is a serious postsurgical issue. Adhesions develop after damage to the peritoneum by surgery, irradiation, infection or trauma. Objectives: Using a rat model, we compared the effectiveness of systemic and intraperitoneally administered common immunosuppressive drugs for prevention of postoperative intraperitoneal adhesions. Materials and Methods: Peritoneal adhesions were induced in 98 female Wistar-Albino rats by cecal abrasion and peritoneal excision. Rats were randomly separated into seven groups, each containing fourteen rats, and the standard experimental model was applied to all of rats. 14 days later, rats were euthanized, intraperitoneal adhesions were scored and tissues were examined histologically using hematoxylin/eosin and Masson’s trichrome staining. Results: Throughout the investigation, no animal died during or after surgery. In all of experimental groups, decrease in fibrosis was statistically significant. Decrease in fibrosis was most prominently in intraperitoneal tacrolimus group (P = 0.000), and decrease was least in intraperitoneal cyclosporine group (P = 0.022). Vascular proliferation was significantly decreased in all experimental groups (P < 0.05) except for systemic tacrolimus group (P = 0.139). Most prominent reduction in vascular proliferation was in intraperitoneal tacrolimus group (P = 0.000). Conclusions: Administration of immunosuppressive drugs is effective for prevention of intraperitoneal adhesions. PMID:24693396

21 CFR 201.115 - New drugs or new animal drugs.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false New drugs or new animal drugs. 201.115 Section 201.115 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING Exemptions From Adequate Directions for Use § 201.115 New drugs or new animal...

Multiple-robot drug delivery strategy through coordinated teams of microswimmers

Energy Technology Data Exchange (ETDEWEB)

Kei Cheang, U; Kim, Min Jun, E-mail: mkim@coe.drexel.edu [Department of Mechanical Engineering and Mechanics, Drexel University, Philadelphia, Pennsylvania 19104 (United States); Lee, Kyoungwoo [Department of Computer Science, Yonsei University, Seoul 120-749 (Korea, Republic of); Julius, Anak Agung [Department of Electrical, Computer and Systems Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180 (United States)

2014-08-25

Untethered robotic microswimmers are very promising to significantly improve various types of minimally invasive surgeries by offering high accuracy at extremely small scales. A prime example is drug delivery, for which a large number of microswimmers is required to deliver sufficient dosages to target sites. For this reason, the controllability of groups of microswimmers is essential. In this paper, we demonstrate simultaneous control of multiple geometrically similar but magnetically different microswimmers using a single global rotating magnetic field. By exploiting the differences in their magnetic properties, we triggered different swimming behaviors from the microswimmers by controlling the frequency and the strength of the global field, for example, one swim and the other does not while exposed to the same control input. Our results show that the balance between the applied magnetic torque and the hydrodynamic torque can be exploited for simultaneous control of two microswimmers to swim in opposite directions, with different velocities, and with similar velocities. This work will serve to establish important concepts for future developments of control systems to manipulate multiple magnetically actuated microswimmers and a step towards using swarms of microswimmers as viable workforces for complex operations.

Multiple-robot drug delivery strategy through coordinated teams of microswimmers

International Nuclear Information System (INIS)

Kei Cheang, U; Kim, Min Jun; Lee, Kyoungwoo; Julius, Anak Agung

2014-01-01

Untethered robotic microswimmers are very promising to significantly improve various types of minimally invasive surgeries by offering high accuracy at extremely small scales. A prime example is drug delivery, for which a large number of microswimmers is required to deliver sufficient dosages to target sites. For this reason, the controllability of groups of microswimmers is essential. In this paper, we demonstrate simultaneous control of multiple geometrically similar but magnetically different microswimmers using a single global rotating magnetic field. By exploiting the differences in their magnetic properties, we triggered different swimming behaviors from the microswimmers by controlling the frequency and the strength of the global field, for example, one swim and the other does not while exposed to the same control input. Our results show that the balance between the applied magnetic torque and the hydrodynamic torque can be exploited for simultaneous control of two microswimmers to swim in opposite directions, with different velocities, and with similar velocities. This work will serve to establish important concepts for future developments of control systems to manipulate multiple magnetically actuated microswimmers and a step towards using swarms of microswimmers as viable workforces for complex operations.

Community-directed mass drug administration is undermined by status seeking in friendship networks and inadequate trust in health advice networks

NARCIS (Netherlands)

Chami, Goylette F.; Kontoleon, Andreas A.; Bulte, Erwin; Fenwick, Alan; Kabatereine, Narcis B.; Tukahebwa, Edridah M.; Dunne, David W.

2017-01-01

Over 1.9 billion individuals require preventive chemotherapy through mass drug administration (MDA). Community-directed MDA relies on volunteer community medicine distributors (CMDs) and their achievement of high coverage and compliance. Yet, it is unknown if village social networks influence

Community-directed mass drug administration is undermined by status seeking in friendship networks and inadequate trust in health advice networks

NARCIS (Netherlands)

Chami, Goylette F.; Kontoleon, Andreas A.; Bulte, Erwin; Fenwick, Alan; Kabatereine, Narcis B.; Tukahebwa, Edridah M.; Dunne, David W.

2017-01-01

Over 1.9 billion individuals require preventive chemotherapy through mass drug administration (MDA). Community-directed MDA relies on volunteer community medicine distributors (CMDs) and their achievement of high coverage and compliance. Yet, it is unknown if village social networks influence

Patient centric drug product design in modern drug delivery as an opportunity to increase safety and effectiveness.

Science.gov (United States)

Stegemann, Sven

2018-06-01

The advances in drug delivery technologies have enabled pharmaceutical scientists to deliver a drug through various administration routes and optimize the drug release and absorption. The wide range of drug delivery systems and dosage forms represent a toolbox of technology for the development of pharmaceutical drug products but might also be a source of medication errors and nonadherence. Patient centric drug product development is being suggested as an important factor to increase therapeutic outcomes. Areas covered: Patients have impaired health and potentially disabilities and they are not medical or pharmaceutical experts but are requested to manage complex therapeutic regimens. As such the application of technology should also serve to reduce complexity, build on patients' intuition and ease of use. Patients form distinct populations based on the targeted disease, disease cluster or age group with specific characteristics or therapeutic contexts. Expert opinion: Establishing a target product and patient profile is essential to guide drug product design development. Including the targeted patient populations in the process is a prerequisite to achieve patient-centric pharmaceutical drug product design. Addressing the needs early on in the product design process, will create more universal design, avoiding the necessity for multiple product presentations to cover the different patient populations.

Nicotine self-administration and reinstatement of nicotine-seeking in male and female rats.

Science.gov (United States)

Feltenstein, Matthew W; Ghee, Shannon M; See, Ronald E

2012-03-01

Tobacco addiction is a relapsing disorder that constitutes a substantial worldwide health problem, with evidence suggesting that nicotine and nicotine-associated stimuli play divergent roles in maintaining smoking behavior in men and women. While animal models of tobacco addiction that utilize nicotine self-administration have become more widely established, systematic examination of the multiple factors that instigate relapse to nicotine-seeking have been limited. Here, we examined nicotine self-administration and subsequent nicotine-seeking in male and female Sprague-Dawley rats using an animal model of self-administration and relapse. Rats lever pressed for nicotine (0.03 and 0.05 mg/kg/infusion, IV) during 15 daily 2-h sessions, followed by extinction of lever responding. Once responding was extinguished, we examined the ability of previously nicotine-paired cues (tone+light), the anxiogenic drug yohimbine (2.5mg/kg, IP), a priming injection of nicotine (0.3mg/kg, SC), or combinations of drug+cues to reinstate nicotine-seeking. Both males and females readily acquired nicotine self-administration and displayed comparable levels of responding and intake at both nicotine doses. Following extinction, exposure to the previously nicotine-paired cues or yohimbine, but not the nicotine-prime alone, reinstated nicotine-seeking in males and females. Moreover, when combined with nicotine-paired cues, both yohimbine and nicotine enhanced reinstatement. No significant sex differences or estrous cycle dependent changes were noted across reinstatement tests. These results demonstrate the ability to reinstate nicotine-seeking with multiple modalities and that exposure to nicotine-associated cues during periods of a stressful state or nicotine can increase nicotine-seeking. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

21 CFR 201.2 - Drugs and devices; National Drug Code numbers.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Drugs and devices; National Drug Code numbers. 201.2 Section 201.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING General Labeling Provisions § 201.2 Drugs and devices; National Drug Code...

Physical compatibility of binary and ternary mixtures of morphine and methadone with other drugs for parenteral administration in palliative care.

Science.gov (United States)

Destro, Massimo; Ottolini, Luca; Vicentini, Lorenza; Boschetti, Silvia

2012-10-01

The parenteral administration of combinations of drugs is often necessary in palliative medicine, particularly in the terminal stage of life, when patients are no longer able to take medication orally. The use of infusers to administer continuous subcutaneous infusions is a well-established practice in the palliative care setting and enables several drugs to be given simultaneously, avoiding the need for repeated administrations and the effects of peaks and troughs in the doses of medication. The method is also appreciated by patients and caregivers in the home care setting because the devices and infusion sites are easy to manage. Despite their frequent use, however, the mixtures of drugs adopted in clinical practice are sometimes not supported by reliable data concerning their chemical and physical compatibility. The present study investigates the chemical compatibility of binary mixtures (morphine with ketorolac) and the physical compatibility of binary (morphine or methadone with ketorolac) or ternary mixtures (morphine with ketorolac and/or haloperidol, and/or dexamethasone, and/or metoclopramide, and/or hyoscine butylbromide) with a view to reducing the aleatory nature of the empirical use of such combinations, thereby increasing their safety and clinical appropriateness.

Contraceptives as possible risk factors for postpartum depression: A retrospective study of the food and drug administration adverse event reporting system, 2004-2015.

Science.gov (United States)

Horibe, Megumi; Hane, Yuuki; Abe, Junko; Matsui, Toshinobu; Kato, Yamato; Ueda, Natsumi; Sasaoka, Sayaka; Motooka, Yumi; Hatahira, Haruna; Hasegawa, Shiori; Kinosada, Yasutomi; Hara, Hideaki; Nakamura, Mitsuhiro

2018-04-01

Postpartum depression is a mood disorder that commonly affects women during the early postpartum period. The objective of this study was to analyse the association of postpartum depression with drugs (including contraceptive devices and implants) with spontaneously reported adverse events reported in the US Food and Drug Administration Adverse Event Reporting System database. Retrospective study. Reports of postpartum depression events between 2004-2015 were analysed with a reporting odds ratio (ROR) algorithm. The Medical Dictionary for Regulatory Activities was used to identify postpartum depression. The reporting odds ratios (95% confidence intervals, CI) of levonorgestrel (an intrauterine device with progestogen), etonogestrel (a hormonal contraceptive implant), sertraline and drospirenone (an oral contraceptive) were 12.5 (8.7-18.0), 14.0 (8.5-22.8), 12.2 (6.5-23.1) and 5.4 (2.7-10.9) respectively. Among the drugs in the US Food and Drug Administration Adverse Event Reporting System database, the use of contraceptives or an intrauterine device with progestogen might convey risk for postpartum depression.

Disposition of the anti-ulcer medications ranitidine, cimetidine, and omeprazole following administration of multiple doses to exercised Thoroughbred horses.

Science.gov (United States)

Knych, H K; Stanley, S D; Arthur, R M; McKemie, D S

2017-01-01

The use of anti-ulcer medications, such as cimetidine, ranitidine, and omeprazole, is common in performance horses. The use of these drugs is regulated in performance horses, and as such a withdrawal time is necessary prior to competition to avoid a medication violation. To the authors' knowledge, there are no reports in the literature describing repeated oral administrations of these drugs in the horse to determine a regulatory threshold and related withdrawal time recommendations. Therefore, the objective of the current study was to describe the disposition and elimination pharmacokinetics of these anti-ulcer medications following oral administration to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 20 mg/kg BID of cimetidine or 8 mg/kg BID of ranitidine, both for seven doses or 2.28 g of omeprazole SID for four doses. Blood samples were collected, serum drug concentrations were determined, and elimination pharmacokinetic parameters were calculated. The serum elimination half-life was 7.05 ± 1.02, 7.43 ± 0.851 and 3.94 ± 1.04 h for cimetidine, ranitidine, and omeprazole, respectively. Serum cimetidine and ranitidine concentrations were above the LOQ and omeprazole and omeprazole sulfide below the LOQ in all horses studied upon termination of sample collection. © 2016 John Wiley & Sons Ltd.

Validation of key behaviourally based mental health diagnoses in administrative data: suicide attempt, alcohol abuse, illicit drug abuse and tobacco use

Directory of Open Access Journals (Sweden)

Kim Hyungjin

2012-01-01

Full Text Available Abstract Background Observational research frequently uses administrative codes for mental health or substance use diagnoses and for important behaviours such as suicide attempts. We sought to validate codes (International Classification of Diseases, 9th edition, clinical modification diagnostic and E-codes entered in Veterans Health Administration administrative data for patients with depression versus a gold standard of electronic medical record text ("chart notation". Methods Three random samples of patients were selected, each stratified by geographic region, gender, and year of cohort entry, from a VHA depression treatment cohort from April 1, 1999 to September 30, 2004. The first sample was selected from patients who died by suicide, the second from patients who remained alive on the date of death of suicide cases, and the third from patients with a new start of a commonly used antidepressant medication. Four variables were assessed using administrative codes in the year prior to the index date: suicide attempt, alcohol abuse/dependence, drug abuse/dependence and tobacco use. Results Specificity was high (≥ 90% for all four administrative codes, regardless of the sample. Sensitivity was ≤75% and was particularly low for suicide attempt (≤ 17%. Positive predictive values for alcohol dependence/abuse and tobacco use were high, but barely better than flipping a coin for illicit drug abuse/dependence. Sensitivity differed across the three samples, but was highest in the suicide death sample. Conclusions Administrative data-based diagnoses among VHA records have high specificity, but low sensitivity. The accuracy level varies by different diagnosis and by different patient subgroup.

Validation of key behaviourally based mental health diagnoses in administrative data: suicide attempt, alcohol abuse, illicit drug abuse and tobacco use.

Science.gov (United States)

Kim, Hyungjin Myra; Smith, Eric G; Stano, Claire M; Ganoczy, Dara; Zivin, Kara; Walters, Heather; Valenstein, Marcia

2012-01-23

Observational research frequently uses administrative codes for mental health or substance use diagnoses and for important behaviours such as suicide attempts. We sought to validate codes (International Classification of Diseases, 9th edition, clinical modification diagnostic and E-codes) entered in Veterans Health Administration administrative data for patients with depression versus a gold standard of electronic medical record text ("chart notation"). Three random samples of patients were selected, each stratified by geographic region, gender, and year of cohort entry, from a VHA depression treatment cohort from April 1, 1999 to September 30, 2004. The first sample was selected from patients who died by suicide, the second from patients who remained alive on the date of death of suicide cases, and the third from patients with a new start of a commonly used antidepressant medication. Four variables were assessed using administrative codes in the year prior to the index date: suicide attempt, alcohol abuse/dependence, drug abuse/dependence and tobacco use. Specificity was high (≥ 90%) for all four administrative codes, regardless of the sample. Sensitivity was ≤75% and was particularly low for suicide attempt (≤ 17%). Positive predictive values for alcohol dependence/abuse and tobacco use were high, but barely better than flipping a coin for illicit drug abuse/dependence. Sensitivity differed across the three samples, but was highest in the suicide death sample. Administrative data-based diagnoses among VHA records have high specificity, but low sensitivity. The accuracy level varies by different diagnosis and by different patient subgroup.

Pathogenesis of Renal Failure in Multiple Myeloma: Any Role of Contrast Media?

Science.gov (United States)

Mussap, Michele; Merlini, Giampaolo

2014-01-01

The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function. PMID:24877060

Pathogenesis of Renal Failure in Multiple Myeloma: Any Role of Contrast Media?

Directory of Open Access Journals (Sweden)

Michele Mussap

2014-01-01

Full Text Available The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function.

Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992; policies, requirements, and administrative procedures; delay of effective date. Final rule; delay of effective date.

Science.gov (United States)

2004-02-23

The Food and Drug Administration (FDA) is further delaying, until December 1, 2006, the effective date of certain requirements of a final rule published in the Federal Register of December 3, 1999 (64 FR 67720). In the Federal Register of May 3, 2000 (65 FR 25639), the agency delayed until October 1, 2001, the effective date of certain requirements in the final rule relating to wholesale distribution of prescription drugs by distributors that are not authorized distributors of record, and distribution of blood derivatives by entities that meet the definition of a "health care entity" in the final rule. The agency further delayed the effective date of these requirements in three subsequent Federal Register notices. Most recently, in the Federal Register of January 31, 2003 (68 FR 4912), FDA delayed the effective date until April 1, 2004. This action further delays the effective date of these requirements until December 1, 2006. The final rule implements the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA), and the Food and Drug Administration Modernization Act of 1997 (the Modernization Act). The agency is taking this action to address concerns about the requirements in the final rule raised by affected parties. As explained in the SUPPLEMENTARY INFORMATION section, FDA is working with stakeholders through its counterfeit drug initiative to facilitate widespread, voluntary adoption of track and trace technologies that will generate a de facto electronic pedigree, including prior transaction history back to the original manufacturer, as a routine course of business. If this technology is widely adopted, it is expected to help fulfill the pedigree requirements of the PDMA and obviate or resolve many of the concerns that have been raised with respect to the final rule by ensuring that an electronic pedigree travels with a drug product at all times. Therefore, it is necessary to delay the effective date of Sec

77 FR 72254 - New Animal Drugs; Updating Tolerances for Residues of New Animal Drugs in Food

Science.gov (United States)

2012-12-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 500, 520, 522, 524, 529, 556, and 558 [Docket No. FDA-2012-N-1067] RIN 0910-AG17 New Animal Drugs; Updating Tolerances for Residues of New Animal Drugs in Food AGENCY: Food and Drug Administration, HHS. ACTION...

77 FR 12063 - Joint Meeting of the Anti-Infective Drugs Advisory Committee and the Nonprescription Drugs...

Science.gov (United States)

2012-02-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Joint Meeting of the Anti-Infective Drugs Advisory Committee and the Nonprescription Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice announces a forthcoming meeting of a public...

Comparison of brand versus generic antiepileptic drug adverse event reporting rates in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

Science.gov (United States)

Rahman, Md Motiur; Alatawi, Yasser; Cheng, Ning; Qian, Jingjing; Plotkina, Annya V; Peissig, Peggy L; Berg, Richard L; Page, David; Hansen, Richard A

2017-09-01

Despite the cost saving role of generic anti-epileptic drugs (AEDs), debate exists as to whether generic substitution of branded AEDs may lead to therapeutic failure and increased toxicity. This study compared adverse event (AE) reporting rates for brand vs. authorized generic (AG) vs. generic AEDs. Since AGs are pharmaceutically identical to brand but perceived as generics, the generic vs. AG comparison minimized potential bias against generics. Events reported to the U.S. Food and Drug Administration Adverse Event Reporting System between January 2004 to March 2015 with lamotrigine, carbamazepine, and oxcarbazepine listed as primary or secondary suspect were classified as brand, generic, or AG based on the manufacturer. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting of labeled AEs compared to reporting these events with all other drugs. The Breslow-Day statistic compared RORs across brand, AG, and other generics using a Bonferroni-corrected Pbrand and generics for all three drugs of interest (Breslow-Day Pbrands and generics have similar reporting rates after accounting for generic perception biases. Disproportional suicide reporting was observed for generics compared with AGs and brand, although this finding needs further study. Copyright © 2017 Elsevier B.V. All rights reserved.

The pre-hospital administration of tranexamic acid to patients with multiple injuries and its effects on rotational thrombelastometry: a prospective observational study in pre-hospital emergency medicine.

Science.gov (United States)

Kunze-Szikszay, Nils; Krack, Lennart A; Wildenauer, Pauline; Wand, Saskia; Heyne, Tim; Walliser, Karoline; Spering, Christopher; Bauer, Martin; Quintel, Michael; Roessler, Markus

2016-10-10

Hyperfibrinolysis (HF) is a major contributor to coagulopathy and mortality in trauma patients. This study investigated (i) the rate of HF during the pre-hospital management of patients with multiple injuries and (ii) the effects of pre-hospital tranexamic acid (TxA) administration on the coagulation system. From 27 trauma patients with pre-hospital an estimated injury severity score (ISS) ≥16 points blood was obtained at the scene and on admission to the emergency department (ED). All patients received 1 g of TxA after the first blood sample was taken. Rotational thrombelastometry (ROTEM) was performed for both blood samples, and the results were compared. HF was defined as a maximum lysis (ML) >15 % in EXTEM. The median (min-max) ISS was 17 points (4-50 points). Four patients (15 %) had HF diagnosed via ROTEM at the scene, and 2 patients (7.5 %) had HF diagnosed via ROTEM on admission to the ED. The median ML before TxA administration was 11 % (3-99 %) vs. 10 % after TxA administration (4-18 %; p > 0.05). TxA was administered 37 min (10-85 min) before ED arrival. The ROTEM results before and after TxA administration did not significantly differ. No adverse drug reactions were observed after TxA administration. HF can be present in severely injured patients during pre-hospital care. Antifibrinolytic therapy administered at the scene is a significant time saver. Even in milder trauma fibrinogen can be decreased to critically low levels. Early administration of TxA cannot reverse or entirely stop this decrease. The pre-hospital use of TxA should be considered for severely injured patients to prevent the worsening of trauma-induced coagulopathy and unnecessarily high fibrinogen consumption. ClinicalTrials.gov ID NCT01938768 (Registered 5 September 2013).

75 FR 14445 - Guidance for Industry on Submitting a Report for Multiple Facilities to the Reportable Food...

Science.gov (United States)

2010-03-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-D-0260] Guidance for Industry on Submitting a Report for Multiple Facilities to the Reportable Food Electronic... Act of 2007.'' The document provides guidance to the industry in complying with the Reportable Food...

An evaluation of adherence in patients with multiple sclerosis newly initiating treatment with a self-injectable or an oral disease-modifying drug

Directory of Open Access Journals (Sweden)

Munsell M

2016-12-01

Full Text Available Michael Munsell,1 Molly Frean,1 Joseph Menzin,1 Amy L Phillips2 1Boston Health Economics, Inc., Waltham, MA, USA; 2Health Economics & Outcomes Research, EMD Serono Inc., Rockland, MA, USA Objective: As the multiple sclerosis (MS disease-modifying drug (DMD treatment options have expanded to include oral therapies, it is important to understand whether route of administration is associated with DMD adherence. The objective of this study was to compare adherence to DMDs in patients with MS newly initiating treatment with a self-injectable versus an oral DMD. Methods: This retrospective database study used IMS Health Real World Data Adjudicated Claims – US data between July 1, 2010 and June 30, 2014. Adherence was measured by medication possession ratio (MPR, calculated as the total number of treated days divided by the total number of days from the first treated day until the end of 12-month follow-up. A binary measure representing adherence (MPR ≥0.8 versus nonadherence (MPR <0.8 to therapy was used. Logistic regression evaluated the likelihood of adherence to index DMD type (self-injectable vs oral. Covariates included patient baseline characteristics (ie, age, sex, comorbidities and index DMD type. Results: The analysis included 7,207 self-injectable and 1,175 oral DMD-treated patients with MS. In unadjusted analyses, the proportion of patients adherent to therapy (MPR ≥0.8 did not differ significantly between the self-injectable (54.1% and the oral DMD cohorts (53.0%; P=0.5075. After controlling for covariates, index DMD type was not a significant predictor of adherence (odds ratio [OR] 1.062; 95% confidence interval [CI]: 0.937–1.202; P=0.3473. Higher likelihood of adherence was associated with male sex (OR 1.20; 95% CI: 1.085–1.335; P=0.0005 and age groups older than 18–34 years (ORs 1.220–1.331; P<0.01. Depression was associated with a lower likelihood of adherence (OR 0.618; 95% CI: 0.511–0.747; P<0.0001. Conclusion: Male

Factors influencing consumer purchasing patterns of generic versus brand name over-the-counter drugs.

Science.gov (United States)

Kohli, Erol; Buller, Allison

2013-02-01

US consumers spend more than $20 billion/year on over-the-counter (OTC) drugs. Although generic and brand name OTC drugs share the same active ingredients and undergo the same rigorous Food and Drug Administration approval process, brand name formulations continue to lead the OTC drug market with a higher market share. There is a limited amount of publicly available information regarding consumer perceptions and awareness about generic and brand name OTC drugs. The main objective of this research was to understand what factors influence US consumers to purchase generic versus brand name OTC drugs. The researchers used a 20-question, self-administered, multiple-choice survey to collect data on the factors influencing consumers' preferences for generic versus brand name OTC drugs. Results revealed that the single most influential factor for participants when purchasing OTC drugs was lower cost. Although economic factors play an important role in influencing consumers to choose generic formulations, a variety of other factors including advertisements, duration of the OTC effectiveness, severity of sickness, preferable form of OTC medication, safety of the OTC, relief of multiple symptoms, and preferred company will persuade others to pay more for brand name drugs. Ultimately, increased awareness and use of generic OTC drugs may result in substantial cost savings for consumers.

The Food and Drug Administration and Drug Legalization: A Brief Model of Regulation

OpenAIRE

Kalam, Murad

2002-01-01

This paper offers a brief model of FDA regulation of currently illegal narcotics in the United States. Given that nearly three out of four Americans believe that the drug war has failed, recent calls from prominent liberal and conservative thinkers to legalize drugs, and state “compassionate use†ballot initiatives, future drug legalization is at least conceivable in the United States. Yet, how would the FDA regulate NLD’s under its current st...

Nanotechnology-based drug delivery systems

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Singh Baljit

2007-12-01

Full Text Available Abstract Nanoparticles hold tremendous potential as an effective drug delivery system. In this review we discussed recent developments in nanotechnology for drug delivery. To overcome the problems of gene and drug delivery, nanotechnology has gained interest in recent years. Nanosystems with different compositions and biological properties have been extensively investigated for drug and gene delivery applications. To achieve efficient drug delivery it is important to understand the interactions of nanomaterials with the biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signalling involved in pathobiology of the disease under consideration. Several anti-cancer drugs including paclitaxel, doxorubicin, 5-fluorouracil and dexamethasone have been successfully formulated using nanomaterials. Quantom dots, chitosan, Polylactic/glycolic acid (PLGA and PLGA-based nanoparticles have also been used for in vitro RNAi delivery. Brain cancer is one of the most difficult malignancies to detect and treat mainly because of the difficulty in getting imaging and therapeutic agents past the blood-brain barrier and into the brain. Anti-cancer drugs such as loperamide and doxorubicin bound to nanomaterials have been shown to cross the intact blood-brain barrier and released at therapeutic concentrations in the brain. The use of nanomaterials including peptide-based nanotubes to target the vascular endothelial growth factor (VEGF receptor and cell adhesion molecules like integrins, cadherins and selectins, is a new approach to control disease progression.

Pavlovian conditioning of multiple opioid-like responses in mice.

Science.gov (United States)

Bryant, Camron D; Roberts, Kristofer W; Culbertson, Christopher S; Le, Alan; Evans, Christopher J; Fanselow, Michael S

2009-07-01

Conditional responses in rodents such as locomotion have been reported for drugs of abuse and similar to the placebo response in humans, may be associated with the expectation of reward. We examined several conditional opioid-like responses and the influence of drug expectation on conditioned place preference and concomitant conditional locomotion. Male C57BL/6J mice were conditioned with the selective mu opioid receptor agonist fentanyl (0.2mg/kg, i.p.) in a novel context and subsequently given a vehicle injection. In separate experiments, locomotor activity, Straub tail, hot plate sensitivity, and conditioned place preference (CPP) were measured. Mice exhibited multiple conditional opioid-like responses including conditional hyperlocomotion, a conditional pattern of opioid-like locomotion, Straub tail, analgesia, and place preference. Modulating drug expectation via administration of fentanyl to "demonstrator" mice in the home cage did not affect the expression of conditioned place preference or the concomitant locomotor activity in "observer" mice. In summary, Pavlovian conditioning of an opioid in a novel context induced multiple conditional opioid-like behaviors and provides a model for studying the neurobiological mechanisms of the placebo response in mice.

Differential modulation of thresholds for intracranial self-stimulation by mGlu5 positive and negative allosteric modulators: implications for effects on drug self-administration

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M. Foster eOlive

2012-01-01

Full Text Available Pharmacological manipulation of the type 5 metabotropic glutamate (mGlu5 receptor alters various addiction related behaviors such as drug self-administration and the extinction and reinstatement of drug-seeking behavior. However, the effects of pharmacological modulation of mGlu5 receptors on brain reward function have not been widely investigated. We examined the effects of acute administration of positive and negative allosteric modulators (PAMs and NAMs, respectively on brain reward function by assessing thresholds for intracranial self-stimulation (ICSS. In addition, when acute effects were observed, we examined potential changes in altered ICSS thresholds following repeated administration. Male Sprague-Dawley rats were implanted with bipolar electrodes into the medial forebrain bundle and trained to respond for ICSS, followed by assessment of effects of mGlu5 ligands on ICSS thresholds using a discrete trials current intensity threshold determination procedure. Acute administration of the selective mGlu5 NAMs MTEP (0, 0.3, 1 or 3 mg/kg and fenobam (0, 3, 10, or 30 mg/kg dose-dependently increased ICSS thresholds (~70% at the highest dose tested, suggesting a deficit in brain reward function. Acute administration of the mGlu5 PAMs CDPPB (0, 10, 30 and 60 mg/kg or ADX47273 (0, 10, 30 and 60 mg/kg was without effect at any dose tested. When administered once daily for 5 consecutive days, the development of tolerance to the ability of threshold-elevating doses of MTEP and fenobam to increase ICSS thresholds was observed. We conclude that mGlu5 PAMs and NAMs differentially affect brain reward function, and that tolerance to the ability of mGlu5 NAMs to reduce brain reward function develops with repeated administration. These brain reward deficits should be taken into consideration when interpreting acute effects of mGlu5 NAMs on drug self-administration, and repeated administration may be an effective method to reduce these deficits.

Combining two technologies: multifunctional polymers and self-nanoemulsifying drug delivery system (SNEDDS) for oral insulin administration.

Science.gov (United States)

Sakloetsakun, Duangkamon; Dünnhaupt, Sarah; Barthelmes, Jan; Perera, Glen; Bernkop-Schnürch, Andreas

2013-10-01

The aim of the study is to develop a self-nanoemulsifying drug delivery system (SNEDDS) based on thiolated chitosan for oral insulin administration. The preparations were characterized by particle size, entrapment efficiency, stability and drug release. Serum insulin concentrations were determined after oral administration of all formulations. Insulin SNEDDS formulation was served as control. The optimized SNEDDS consists of 65% (w/w) miglyol 840, 25% (w/w) cremophor EL, 10% (w/w) co-solvents (a mixture of DMSO and glycerol). The formulations in the presence or absence of insulin (5mg/mL) were spherical with the size range between 80 and 160 nm. Entrapment efficiency of insulin increased significantly when the thiolated chitosan was employed (95.14±2.96%), in comparison to the insulin SNEDDS (80.38±1.22%). After 30 min, the in vitro release profile of insulin from the nanoemulsions was markedly increased compared to the control. In vivo results showed that insulin/thiolated chitosan SNEDDS displayed a significant increase in serum insulin (p-value=0.02) compared to oral insulin solution. A new strategy to combine SNEDDS and thiolated chitosan described in the study would therefore be a promising and innovative approach to improve oral bioavailability of insulin. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

THE DRUG-INDUCED HEPATITIS IN CHILDREN

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O. V. Molochkova

2017-01-01

Full Text Available Among toxic lesions of the liver, an important place belongs to medicinal hepatitis. Among patients with hepatitis, drug disease of the liver occurs in 0.7—1.4% of cases, and in the presence of jaundice — in 5%. A family case of sisters 9 and 4-year-old life development  of acute drug hepatitis caused by ibuprofen in a daily dose of 32 mg / kg (total 3.2 g and 25 mg / kg (total 2 g, respectively, was demonstrated in siblings. Hepatitis developed after an acute respiratory infection. Weakness, nausea, vomiting, jaundice of the skin and sclera, pruritus, multiple increase in serum transaminases and markers of cholestasis are revealed. Viral hepatitis and some hereditary liver diseases were excluded. The drug lesion of the liver was of a mixed nature: hepatocellular (cytotoxic and cholestatic. Timely administration of therapy (detoxification, glucocorticosteroids, ursodeoxycholic acid (Ursosan led to a regression of clinical symptoms of the disease and positive dynamics of laboratory indicators.

PRESYNAPTIC DOPAMINE MODULATION BY STIMULANT SELF ADMINISTRATION

Science.gov (United States)

España, Rodrigo A.; Jones, Sara R.

2013-01-01

The mesolimbic dopamine system is an essential participant in the initiation and modulation of various forms of goal-directed behavior, including drug reinforcement and addiction processes. Dopamine neurotransmission is increased by acute administration of all drugs of abuse, including the stimulants cocaine and amphetamine. Chronic exposure to these drugs via voluntary self-administration provides a model of stimulant abuse that is useful in evaluating potential behavioral and neurochemical adaptations that occur during addiction. This review describes commonly used methodologies to measure dopamine and baseline parameters of presynaptic dopamine regulation, including exocytotic release and reuptake through the dopamine transporter in the nucleus accumbens core, as well as dramatic adaptations in dopamine neurotransmission and drug sensitivity that occur with acute non-contingent and chronic, contingent self-administration of cocaine and amphetamine. PMID:23277050

Administrative Data Repository (ADR)

Data.gov (United States)

Department of Veterans Affairs — The Administrative Data Repository (ADR) was established to provide support for the administrative data elements relative to multiple categories of a person entity...

Multiple drug cost containment policies in Michigan's Medicaid program saved money overall, although some increased costs.

Science.gov (United States)

Kibicho, Jennifer; Pinkerton, Steven D

2012-04-01

Michigan's Medicaid program implemented four cost containment policies--preferred drug lists, joint and multistate purchasing arrangements, and maximum allowable cost--during 2002-04. The goal was to control growth of drug spending for beneficiaries who were enrolled in both Medicaid and Medicare and taking antihypertensive or antihyperlipidemic prescription drugs. We analyzed the impact of each policy while holding the effect of all other policies constant. Preferred drug lists increased both preferred and generic drugs' market share and reduced daily cost--the cost per day for each prescription provided to a beneficiary. In contrast, the maximum allowable cost policy increased daily cost and was the only policy that did not generate cost savings. The joint and multistate arrangements did not affect daily cost. Despite these policy trade-offs, the cumulative effect was a 10 percent decrease in daily cost and a total cost savings of $46,195 per year. Our findings suggest that policy makers need to evaluate the impact of multiple policies aimed at restraining drug spending, and further evaluate the policy trade-offs, to ensure that scarce public dollars achieve the greatest return for money spent.

The reduction of radiation damage to the spinal cord by post-irradiation administration of vasoactive drugs

International Nuclear Information System (INIS)

Hornsey, S.; Myers, R.; Jenkinson, T.

1990-01-01

Radiation induced white matter necrosis in the rat spinal cord is preceded by changes in permeability of the blood brain-barrier, reduced blood flow, and infarction so that the necrosis is an ischemic necrosis. Attempts have been made to modify this developing pathology by the administration of drugs post-irradiation but just prior to the changes in vascular permeability. Verapamyl, a calcium channel blocker, had no effect on the development of ataxia. Dipyridamole, a drug which increases blood flow and reduces thrombosis, delayed and reduced the onset of ataxia. A low iron diet and desferrioxamine which reduces reperfusion injury also delayed and reduced ataxia. These results support the thesis that vascular changes are an important pathway in the development of radiation necrosis and that reperfusion injury is an important factor in the development and exacerbation of radiation damage to the spinal cord

The impact of the Food and Drug Administration Modernization Act on the recruitment of children for research.

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Sharav, Vera Hassner

2003-01-01

This article argues that contrary to the claims made by research stakeholders in industry, academia and government, the shift in public policy since the enactment of the Food and Drug Administration Modernization Act (FDAMA) of 1997 and its financial incentives to industry to test drugs on children, has had a deleterious impact on children's dignity, health and welfare. Those lucrative incentives offered an opportunity to accelerate the pace of FDA approval for pediatric drug marketing. FDAMA resulted in a radical shift in federal policy to accommodate an expansion of pediatric trials. Children who are precluded from exercising a human adult's right to informed consent to research are increasingly sought as test subjects even when the trials offer no potential benefit for them. Prior to FDAMA children were protected under federal regulations that prohibited their recruitment for experiments that were not in their best interest. This article discusses eight cases and controversies demonstrating that children have been subjected to experiments that exposed them to pain, discomfort, and serious risks of harm. Babies have died testing a lethal heartburn drug; children have been subjected to "forced dose titration" in antidepressant drug trials that resulted in several suicide attempts. Toddlers are currently being subjected to methylphenidate dose tolerance tests without evidence of any pathological condition. Healthy teenagers are being exposed to antipsychotic drugs known to induce severe pathological side effects in speculative "schizophrenia prevention" experiments.

Brain energy metabolism is activated after acute and chronic administration of fenproporex in young rats.

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Rezin, Gislaine T; Jeremias, Isabela C; Ferreira, Gabriela K; Cardoso, Mariane R; Morais, Meline O S; Gomes, Lara M; Martinello, Otaviana B; Valvassori, Samira S; Quevedo, João; Streck, Emilio L

2011-12-01

Obesity is a chronic disease of multiple etiologies, including genetic, metabolic, environmental, social, and other factors. Pharmaceutical strategies in the treatment of obesity include drugs that regulate food intake, thermo genesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine. Studies suggest that amphetamine induces neurotoxicity through generation of free radicals and mitochondrial apoptotic pathway by cytochrome c release, accompanied by a decrease of mitochondrial membrane potential. Mitochondria are intracellular organelles that play a crucial role in ATP production. Thus, in the present study we evaluated the activities of some enzymes of Krebs cycle, mitochondrial respiratory chain complexes and creatine kinase in the brain of young rats submitted to acute and chronic administration of fenproporex. In the acute administration, the animals received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or tween. In the chronic administration, the animals received a single injection daily for 14 days of fenproporex (6.25, 12.5 or 25 mg/Kg i.p.). Two hours after the last injection, the rats were sacrificed by decapitation and the brain was removed for evaluation of biochemical parameters. Our results showed that the activities of citrate synthase, malate dehydrogenase and succinate dehydrogenase were increased by acute and chronic administration of fenproporex. Complexes I, II, II-III and IV and creatine kinase activities were also increased after acute and chronic administration of the drug. Our results are consistent with others reports that showed that some psychostimulant drugs increased brain energy metabolism in young rats. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

Clinical trials for vaccine development in registry of Korea Food and Drug Administration.

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Kang, Seog-Youn

2013-01-01

Based on the action plan "Ensuring a stable supply of National Immunization Program vaccines and sovereignty of biopharmaceutical products," Korea Food and Drug Administration (KFDA) has made efforts to develop vaccines in the context of self reliance and to protect public health. Along with the recognized infrastructures for clinical trials, clinical trials for vaccines have also gradually been conducted at multinational sites as well as at local sites. KFDA will support to expand six to eleven kinds of vaccines by 2017. In accordance with integrated regulatory system, KFDA has promoted clinical trials, established national lot release procedure, and strengthened good manufacturing practices inspection and post marketing surveillance. Against this backdrop, KFDA will support the vaccine development and promote excellent public health protection.

Predicted Impact of the Food and Drug Administration's Menu-Labeling Regulations on Restaurants in 4 New Jersey Cities.

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Gruner, Jessie; DeWeese, Robin S; Lorts, Cori; Yedidia, Michael J; Ohri-Vachaspati, Punam

2018-02-01

To determine the proportion of restaurants that will be required to post calorie information under the Food and Drug Administration's menu-labeling regulations in 4 New Jersey cities. We classified geocoded 2014 data on 1753 restaurant outlets in accordance with the Food and Drug Administration's guidelines, which will require restaurants with 20 or more locations nationwide to post calorie information. We used multivariate logistic regression analyses to assess the association between menu-labeling requirements and census tract characteristics. Only 17.6% of restaurants will be affected by menu labeling; restaurants in higher-income tracts have higher odds than do restaurants in lower-income tracts (odds ratio [OR] = 1.55; P = .02). Restaurants in non-Hispanic Black (OR = 1.62; P = .02) and mixed race/ethnicity (OR = 1.44; P = .05) tracts have higher odds than do restaurants in non-Hispanic White tracts of being affected. Additional strategies are needed to help consumers make healthy choices at restaurants not affected by the menu-labeling law. These findings have implications for designing implementation strategies for the law and for evaluating its impact.

Laboratory-based testing to evaluate abuse-deterrent formulations and satisfy the Food and Drug Administration's recommendation for Category 1 Testing.

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Altomare, Christopher; Kinzler, Eric R; Buchhalter, August R; Cone, Edward J; Costantino, Anthony

The US Food and Drug Administration (FDA) considers the development of abuse-deterrent formulations of solid oral dosage forms a public health priority and has outlined a series of premarket studies that should be performed prior to submitting an application to the Agency. Category 1 studies are performed to characterize whether the abuse-deterrent properties of a new formulation can be easily defeated. Study protocols are designed to evaluate common abuse patterns of prescription medications as well as more advanced methods that have been reported on drug abuse websites and forums. Because FDA believes Category 1 testing should fully characterize the abuse-deterrent characteristics of an investigational formulation, Category 1 testing is time consuming and requires specialized laboratory resources as well as advanced knowledge of prescription medication abuse. Recent Advisory Committee meetings at FDA have shown that Category 1 tests play a critical role in FDA's evaluation of an investigational formulation. In this article, we will provide a general overview of the methods of manipulation and routes of administration commonly utilized by prescription drug abusers, how those methods and routes are evaluated in a laboratory setting, and discuss data intake, analysis, and reporting to satisfy FDA's Category 1 testing requirements.

Drug repurposing: a systematic approach to evaluate candidate oral neuroprotective interventions for secondary progressive multiple sclerosis.

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Hanna M Vesterinen

Full Text Available To develop and implement an evidence based framework to select, from drugs already licenced, candidate oral neuroprotective drugs to be tested in secondary progressive multiple sclerosis.Systematic review of clinical studies of oral putative neuroprotective therapies in MS and four other neurodegenerative diseases with shared pathological features, followed by systematic review and meta-analyses of the in vivo experimental data for those interventions. We presented summary data to an international multi-disciplinary committee, which assessed each drug in turn using pre-specified criteria including consideration of mechanism of action.We identified a short list of fifty-two candidate interventions. After review of all clinical and pre-clinical evidence we identified ibudilast, riluzole, amiloride, pirfenidone, fluoxetine, oxcarbazepine, and the polyunsaturated fatty-acid class (Linoleic Acid, Lipoic acid; Omega-3 fatty acid, Max EPA oil as lead candidates for clinical evaluation.We demonstrate a standardised and systematic approach to candidate identification for drug rescue and repurposing trials that can be applied widely to neurodegenerative disorders.

Drugs Approved for Neuroblastoma

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