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Sample records for once-daily mometasone furoate

  1. Mometasone furoate in the management of asthma: a review

    Ricardo A Tan

    2008-09-01

    Full Text Available Ricardo A Tan1, Jonathan Corren21California Allergy and Asthma Medical Group, Los Angeles, CA; 2Allergy Research Foundation, Los Angeles, CA, USAAbstract: Inhaled corticosteroids (ICS have proven to be the most effective and essential therapy for the treatment of bronchial asthma. The 2007 National Asthma Education and Prevention Program guidelines recommend ICS as preferred therapy for patients with mild to severe persistent asthma. Mometasone furoate (MF is a relatively new ICS agent with high affinity for the glucocorticoid receptor. It is approved in the US for maintenance treatment of asthma for patients 4 years of age and older. It has been shown to be well tolerated with no significant adverse side effects observed in clinical trials and post-marketing surveillance. The efficacy of mometasone furoate has been established in large, well-designed studies. In patients with persistent asthma previously treated either with short-acting beta-agonists alone or twice-daily maintenance therapy with ICS, once-daily MF has been shown to be superior to placebo in improving lung function, symptom control, and quality of life; and has shown comparable efficacy compared with budesonide, beclomethasone, and fluticasone. Twice-daily dosing with MF has been demonstrated to successfully allow for reduction or elimination of oral corticosteroids in severe asthmatics.Keywords: inhaled steroids, mometasone furoate, once-daily dosing, asthma, stepwise approach

  2. Mometasone furoate nasal spray for the treatment of asthma

    Meteran, Howraman; Backer, Vibeke

    2016-01-01

    are the key stone in the treatment of both diseases. Mometasone furoate is a potent synthetic steroid with a very high receptor affinity and a low bioavailability and shown to be superior compared to other inhaled corticosteroids. It is not clear whether the use of mometasone furoate nasal spray (MFNS......) is associated with an improvement in asthma control. AREAS COVERED: This current paper reviews the current knowledge on the effect of mometasone furoate nasal spray in the treatment of asthma and includes clinical trials in which both subjective and objective outcomes are assessed. EXPERT OPINION: To date, only...

  3. Randomized Trial of Once-Daily Fluticasone Furoate in Children with Inadequately Controlled Asthma

    Oliver, Amanda J.; Covar, Ronina A.; Goldfrad, Caroline H.

    2016-01-01

    Objective To evaluate the dose-response, efficacy, and safety of fluticasone furoate (FF; 25 µg, 50 µg, and 100 µg), administered once daily in the evening during a 12-week treatment period to children with inadequately controlled asthma. Study design This was a Phase IIb, multicenter, stratified...

  4. Fluticasone furoate: once-daily evening treatment versus twice-daily treatment in moderate asthma

    Woodcock Ashley

    2011-12-01

    Full Text Available Abstract Background Inhaled corticosteroids are the recommended first-line treatment for asthma but adherence to therapy is suboptimal. The objectives of this study were to compare the efficacy and safety of once-daily (OD evening and twice-daily (BD regimens of the novel inhaled corticosteroid fluticasone furoate (FF in asthma patients. Methods Patients with moderate asthma (age ≥ 12 years; pre-bronchodilator forced expiratory volume in 1 second (FEV1 40-85% predicted; FEV1 reversibility of ≥ 12% and ≥ 200 ml were randomized to FF or fluticasone propionate (FP regimens in a double-blind, crossover study. Patients were not permitted to have used any ICS for ≥ 8 weeks prior to enrolment and subsequently received doses of FF or FP 200 μg OD, FF or FP 100 μg BD and matching placebo by inhalation for 28 days each. Primary endpoint was Day 28 evening pre-dose (trough FEV1; non-inferiority of FF 200 μg OD and FF 100 μg BD was assessed, as was superiority of all active treatment relative to placebo. Adverse events (AEs and 24-hour urinary cortisol excretion were assessed. Results The intent-to-treat population comprised 147 (FF and 43 (FP patients. On Day 28, pre-dose FEV1 showed FF 200 μg OD to be non-inferior (pre-defined limit -110 ml to FF 100 μg BD (mean treatment difference 11 ml; 95% CI: -35 to +56 ml; all FF and FP regimens were significantly superior to placebo (p ≤ 0.02. AEs were similar to placebo; no serious AEs were reported. Urinary cortisol excretion at Day 28 for FF was lower than placebo (ratios: 200 μg OD, 0.75; 100 μg BD, 0.84; p ≤ 0.02. Conclusions FF 200 μg OD in the evening is an efficacious and well tolerated treatment for asthma patients and is not inferior to the same total BD dose. Trial registration Clinicaltrials.gov; NCT00766090.

  5. Regional deposition of mometasone furoate nasal spray suspension in humans.

    Shah, Samir A; Berger, Robert L; McDermott, John; Gupta, Pranav; Monteith, David; Connor, Alyson; Lin, Wu

    2015-01-01

    Nasal deposition studies can demonstrate whether nasal sprays treating allergic rhinitis and polyposis reach the ciliated posterior nasal cavity, where turbinate inflammation and other pathology occurs. However, quantifying nasal deposition is challenging, because in vitro tests do not correlate to human nasal deposition; gamma scintigraphy studies are thus used. For valid data, the radiolabel must distribute, as the drug, into different-sized droplets, remain associated with the drug in the formulation after administration, and not alter its deposition. Some nasal deposition studies have demonstrated this using homogenous solutions. However, most commercial nasal sprays are heterogeneous suspensions. Using mometasone furoate nasal suspension (MFS), we developed a technique to validate radiolabel deposition as a surrogate for nasal cavity drug deposition and characterized regional deposition and nasal clearance in humans. Mometasone furoate (MF) formulation was spiked with diethylene triamine pentacaetic acid. Both unlabeled and radiolabeled formulations (n = 3) were sprayed into a regionally divided nasal cast. Drug deposition was quantified by high pressure liquid chromatography within each region; radiolabel deposition was determined by gamma camera. Healthy subjects (n = 12) were dosed and imaged for six hours. Scintigraphic images were coregistered with magnetic resonance imaging scans to quantify anterior and posterior nasal cavity deposition and mucociliary clearance. The ratio of radiolabel to unlabeled drug was 1.05 in the nasal cast and regionally appeared to match, indicating that in vivo radiolabel deposition could represent drug deposition. In humans, MFS delivered 86% (9.2) of metered dose to the nasal cavity, approximately 60% (9.1) of metered dose to the posterior nasal cavity. After 15 minutes, mucociliary clearance removed 59% of the initial radiolabel in the nasal cavity, consistent with clearance rates from the ciliated posterior surface. MFS

  6. Mometasone furoate nasal spray relieves the ocular symptoms of seasonal allergic rhinoconjunctivitis.

    Igarashi, Tsutomu; Nakazato, Yuri; Kunishige, Tomoyuki; Fujita, Miho; Yamada, Yumi; Fujimoto, Chiaki; Okubo, Kimihiro; Takahashi, Hiroshi

    2012-01-01

    Recent studies have examined the effects of intranasal corticosteroids (INSs) in relieving the ocular symptoms of seasonal allergic rhinoconjunctivitis (SAR) and perennial allergic rhinitis. However, because most of these studies were based on subjective assessments by patients, the associated factors and mechanism of action are unknown. A single-center, randomized, double-blind, parallel-group study was carried out in which patients with SAR were randomly assigned to an INS mometasone furoate nasal spray (MFNS) group or to a placebo group and treated once daily for 4 weeks. Substance P concentrations in tears were measured, ocular and nasal symptoms were recorded by patients in an allergy diary, and findings were recorded by an ophthalmologist. There was no significant difference between treatment groups in the mean change from baseline of substance P concentration in tears after 4 weeks of treatment, but the mean change tended to increase in the placebo group and tended to decrease in the MFNS group (P = 0.089). All ocular and nasal symptom scores, except eye tearing, were significantly lower in the MFNS group than in the placebo group. Furthermore, substance P concentrations were strongly correlated with ocular and nasal symptom scores. In patients with SAR, INSs tend to decrease the substance P concentration in tears, which is correlated with the severity of ocular and nasal symptoms.

  7. Nasal allergies and beyond: a clinical review of the pharmacology, efficacy, and safety of mometasone furoate

    van Drunen, C.; Meltzer, E. O.; Bachert, C.; Bousquet, J.; Fokkens, W. J.

    2005-01-01

    Mometasone furoate nasal spray (MFNS; Nasonex, Schering-Plough Corporation, Kenilworth, NJ, USA) is an effective and well-tolerated intranasal corticosteroid approved for the prophylactic treatment of seasonal allergic rhinitis, and the treatment of perennial allergic rhinitis. MFNS is a potent

  8. Potent corticosteroid cream (mometasone furoate) significantly reduces acute radiation dermatitis: results from a double-blind, randomized study

    Bostroem, Aasa; Lindman, Henrik; Swartling, Carl; Berne, Berit; Bergh, Jonas

    2001-01-01

    Purpose: Radiation-induced dermatitis is a very common side effect of radiation therapy, and may necessitate interruption of the therapy. There is a substantial lack of evidence-based treatments for this condition. The aim of this study was to investigate the effect of mometasone furoate cream (MMF) on radiation dermatitis in a prospective, double-blind, randomized study. Material and methods: The study comprised 49 patients with node-negative breast cancer. They were operated on with sector resection and scheduled for postoperative radiotherapy using photons with identical radiation qualities and dosage to the breast parenchyma. The patients were randomized to receive either MMF or emollient cream. The cream was applied on the irradiated skin twice a week from the start of radiotherapy until the 12th fraction (24 Gy) and thereafter once daily until 3 weeks after completion of radiation. Both groups additionally received non-blinded emollient cream daily. The intensity of the acute radiation dermatitis was evaluated on a weekly basis regarding erythema and pigmentation, using a reflectance spectrophotometer together with visual scoring of the skin reactions. Results: MMF in combination with emollient cream treatment significantly decreased acute radiation dermatitis (P=0.0033) compared with emollient cream alone. There was no significant difference in pigmentation between the two groups. Conclusions: Adding MMF, a potent topical corticosteroid, to an emollient cream is statistically significantly more effective than emollient cream alone in reducing acute radiation dermatitis

  9. Effect of intranasal mometasone furoate administered in children with coexisting allergic rhinitis and asthma towards asthma attacks and lung function

    Ellen P. Gandaputra

    2009-12-01

    during the study. There was >50% improvement in allergic rhinitis symptoms after 4 weeks of treatment (P50% after 8 weeks of treatment (P50% of asthma symptoms, however it is not followed with significant improvement in lung function. No side effects are reported during 8 weeks use of intranasal mometasone furoate.

  10. Spotlight on fluticasone furoate/vilanterol trifenatate for the once-daily treatment of asthma: design, development and place in therapy

    Albertson TE

    2016-12-01

    Full Text Available Timothy E Albertson,1–3 Samuel W Bullick,1,3 Michael Schivo,1 Mark E Sutter2,3 1Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, 2Department of Emergency Medicine, School of Medicine, UC Davis, Sacramento, 3Department of Medicine, Veterans Administration Northern California Health Care System, Mather, CA, USA Abstract: The use of inhaled corticosteroids (ICSs plays a key role in the treatment of asthmatic patients, and international guidelines have designated ICSs as an early maintenance therapy in controlling asthma symptoms. When asthmatic patients remain symptomatic on ICSs, one common option is to add a long-acting beta2 agonist (LABA to the maintenance treatment. Fixed combination inhalers that contain both an ICS and a LABA have been popular for both chronic obstructive pulmonary disease (COPD and asthma. Historically, these inhalers have been dosed twice daily. However, currently, there is a once-daily combination therapy with the ICS fluticasone furoate (FF and the LABA vilanterol trifenatate (VI with indications for use in both COPD and asthma. This dry powder inhaler (DPI comes in two doses of FF (100 or 200 µg both combined with VI (25 µg. This article reviews the clinical trial data for FF, VI and FF/VI combination inhalers and documents the efficacy and safety of once-daily inhaled maintenance therapy by DPI in asthmatic patients. Keywords: fluticasone furoate/vilanterol trifenatate, asthma, long-acting beta2 agonist, inhaled corticosteroid, combined inhaler, persistent asthma, dry powder inhaler  

  11. Comparative potency of formulations of mometasone furoate in terms of inhibition of ′PIRHR′ in the forearm skin of normal human subjects measured with laser doppler velocimetry

    Kulhalli Prabhakar

    2005-01-01

    Full Text Available BACKGROUND AND AIMS: Topical glucocorticoid formulations are widely used for effective treatment and control of a variety of dermatoses. Mometasone furoate is a newer corticoid that has high potency but low systemic toxicity. Pharmaceutical factors are known to significantly influence potency and systemic absorption of topically applied glucocorticoids. We studied the potency of "Elocon", a topical formulation of mometasone furoate, compared with two other branded formulations of the same corticoid. METHODS: Corticoid potency was measured by employing a pharmacodynamic parameter of an inhibitory effect of the corticoid on post-ischemic-reactive-hyperemic-response (PIRHR in human forearm skin under occlusive dressing. The PIRHR was expressed in terms of % increase in the skin blood flow (SBF as measured with laser doppler velocimetry (LDV. RESULTS : All three active branded formulations of mometasone furoate produced significant inhibition of PIRHR. The AUC(0-2min of PIRHR was ( Mean ± SEM , Control = 213.52 ± 11.80, Placebo = 209.77 ± 19.31, Formulation A = 119.83 ± 13.71, Formulation C = 53.67 ± 4.85 and Formulation D = 111.46 ± 22.87. Formulation "C" exhibited significantly higher topical anti-inflammatory potency than formulations "A" or "D". CONCLUSIONS: Thus, branded formulations of the same glucocorticoid, mometasone furoate significantly differed in their topical anti-inflammatory potency. "Elocon" was significantly more potent than the two other branded formulations studied.

  12. Forced degradation of mometasone furoate and development of two RP-HPLC methods for its determination with formoterol fumarate or salicylic acid

    Ramzia I. El-Bagary

    2016-05-01

    Full Text Available Two simple, selective and precise stability-indicating reversed-phase liquid chromatographic methods were developed and validated for the determination of mometasone furoate in two binary mixtures, with formoterol fumarate (Mixture 1 and salicylic acid (Mixture 2. Also, a forced degradation study of mometasone furoate was carried out including acid and alkali hydrolysis, oxidation, thermal and photo-degradation. For mixture 1, the method was based on isocratic elution using a mobile phase consisting of (Acetonitrile: 3 mM Sodium lauryl sulfate (60:40, v/v at a flow rate of 1 ml min−1. Quantitation was achieved applying dual wavelength detection where mometasone furoate and its degradation products were detected at 247 nm and formoterol fumarate and its degradation product were detected at 214 nm at 30 °C. For mixture 2 and for the forced degradation study, separation was based on isocratic elution of mometasone furoate, its degradation products and salicylic acid on a reversed phase C8 column using a mobile phase consisting of acetonitrile:water:methanol:glacial acetic acid (60:30:10:0.1, v/v at a flow rate of 2 mL min−1. Quantitation was achieved with UV detection at 240 nm. In addition, products from alkaline forced degradation of mometasone furoate were verified by LC–MS. Linearity, accuracy and precision were found to be acceptable over the concentration range of 10–800 μg mL−1 and 5–60 μg mL−1 for mometasone furoate and formoterol fumarate, respectively and over the concentration range of 5–320 μg mL−1 and 20–1280 μg mL−1 for mometasone furoate and salicylic acid, respectively. The two proposed methods could be successfully applied for the routine analysis of the studied drugs in their pharmaceutical preparations without any preliminary separation step.

  13. Validated high-performance thin-layer chromatographic (HPTLC method for simultaneous determination of nadifloxacin, mometasone furoate, and miconazole nitrate cream using fractional factorial design

    Kalpana G. Patel

    2016-07-01

    Full Text Available A high-performance thin-layer chromatographic method for simultaneous determination of nadifloxacin, mometasone furoate, and miconazole nitrate was developed and validated as per International Conference on Harmonization guidelines. High-performance thin-layer chromatographic separation was performed on aluminum plates precoated with silica gel 60F254 and methanol:ethyl acetate:toluene: acetonitrile:3M ammonium formate in water (1:2.5:6.0:0.3:0.2, % v/v as optimized mobile phase at detection wavelength of 224 nm. The retardation factor (Rf values for nadifloxacin, mometasone furoate, and miconazole nitrate were 0.23, 0.70, and 0.59, respectively. Percent recoveries in terms of accuracy for the marketed formulation were found to be 98.35–99.76%, 99.36–99.65%, and 99.16–100.25% for nadifloxacin, mometasone furoate, and miconazole nitrate, respectively. The pooled percent relative standard deviation for repeatability and intermediate precision studies was found to be < 2% for three target analytes. The effect of four independent variables, methanol content in total mobile phase, wavelength, chamber saturation time, and solvent front, was evaluated by fractional factorial design for robustness testing. Amongst all four factors, volume of methanol in mobile phase appeared to have a possibly significant effect on retention factor of miconazole nitrate compared with the other two drugs nadifloxacin and mometasone furoate, and therefore it was important to be carefully controlled. In summary, a novel, simple, accurate, reproducible, and robust high-performance thin-layer chromatographic method was developed, which would be of use in quality control of these cream formulations.

  14. Mometasone Furoate Cream Reduces Acute Radiation Dermatitis in Patients Receiving Breast Radiation Therapy: Results of a Randomized Trial

    Hindley, Andrew; Zain, Zakiyah; Wood, Lisa; Whitehead, Anne; Sanneh, Alison; Barber, David; Hornsby, Ruth

    2014-01-01

    Purpose: We wanted to confirm the benefit of mometasone furoate (MF) in preventing acute radiation reactions, as shown in a previous study (Boström et al, Radiother Oncol 2001;59:257-265). Methods and Materials: The study was a double-blind comparison of MF with D (Diprobase), administered daily from the start of radiation therapy for 5 weeks in patients receiving breast radiation therapy, 40 Gy in 2.67-Gy fractions daily over 3 weeks. The primary endpoint was mean modified Radiation Therapy Oncology Group (RTOG) score. Results: Mean RTOG scores were significantly less for MF than for D (P=.046). Maximum RTOG and mean erythema scores were significantly less for MF than for D (P=.018 and P=.012, respectively). The Dermatology Life Quality Index (DLQI) score was significantly less for MF than for D at weeks 4 and 5 when corrected for Hospital Anxiety and Depression (HAD) questionnaire scores. Conclusions: MF cream significantly reduces radiation dermatitis when applied to the breast during and after radiation therapy. For the first time, we have shown a significantly beneficial effect on quality of life using a validated instrument (DLQI), for a topical steroid cream. We believe that application of this cream should be the standard of care where radiation dermatitis is expected

  15. Mometasone Furoate Cream Reduces Acute Radiation Dermatitis in Patients Receiving Breast Radiation Therapy: Results of a Randomized Trial

    Hindley, Andrew, E-mail: andrew.hindley@lthtr.nhs.uk [Rosemere Cancer Centre, Royal Preston Hospital, Preston (United Kingdom); Zain, Zakiyah [College of Arts and Sciences, Universiti Utara Malaysia, Kedah (Malaysia); Wood, Lisa [Department of Social Sciences, Lancaster Medical School, Lancaster (United Kingdom); Whitehead, Anne [Medical and Pharmaceutical Statistics Research Unit, Lancaster University, Lancaster (United Kingdom); Sanneh, Alison; Barber, David; Hornsby, Ruth [Rosemere Cancer Centre, Royal Preston Hospital, Preston (United Kingdom)

    2014-11-15

    Purpose: We wanted to confirm the benefit of mometasone furoate (MF) in preventing acute radiation reactions, as shown in a previous study (Boström et al, Radiother Oncol 2001;59:257-265). Methods and Materials: The study was a double-blind comparison of MF with D (Diprobase), administered daily from the start of radiation therapy for 5 weeks in patients receiving breast radiation therapy, 40 Gy in 2.67-Gy fractions daily over 3 weeks. The primary endpoint was mean modified Radiation Therapy Oncology Group (RTOG) score. Results: Mean RTOG scores were significantly less for MF than for D (P=.046). Maximum RTOG and mean erythema scores were significantly less for MF than for D (P=.018 and P=.012, respectively). The Dermatology Life Quality Index (DLQI) score was significantly less for MF than for D at weeks 4 and 5 when corrected for Hospital Anxiety and Depression (HAD) questionnaire scores. Conclusions: MF cream significantly reduces radiation dermatitis when applied to the breast during and after radiation therapy. For the first time, we have shown a significantly beneficial effect on quality of life using a validated instrument (DLQI), for a topical steroid cream. We believe that application of this cream should be the standard of care where radiation dermatitis is expected.

  16. Impact of mometasone furoate nasal spray on individual ocular symptoms of allergic rhinitis: a meta-analysis.

    Bielory, L; Chun, Y; Bielory, B P; Canonica, G W

    2011-05-01

    Intranasal corticosteroids (INSs) are a mainstay of treatment of allergic rhinitis (AR) nasal symptoms. The INS mometasone furoate nasal spray (MFNS) has well-documented efficacy and safety for the treatment and prophylaxis of nasal symptoms of seasonal AR (SAR) and for the treatment of nasal symptoms of perennial AR (PAR). Increasing interest has focused on whether INSs, including MFNS, may have beneficial effects on the ocular symptoms frequently associated with AR. We performed a meta-analysis of 10 randomized, placebo-controlled trials of the efficacy of MFNS 200 mcg daily in relieving ocular allergy symptoms, including itching/burning, redness, and tearing/watering in both SAR and PAR. Four PAR studies and six SAR studies are included in the analysis. A fixed-effect inverse variance model was used to calculate weighted mean differences, 95% confidence intervals (CIs) for each comparison, and a combined overall treatment effect (Z) with P-value. In both analyses of SAR and PAR studies, including 3132 patients, all individual ocular symptoms were reduced in patients treated with MFNS. Overall treatment effect was significant for all three individual ocular symptoms in the SAR studies (Z = 9.18 for tearing, Z = 10.15 for itching, and Z = 8.88 for redness; P INSs, including MFNS, on ocular symptoms associated with SAR and PAR. © 2011 John Wiley & Sons A/S.

  17. 21 CFR 524.1610 - Orbifloxacin, mometasone furoate monohydrate, and posaconazole suspension.

    2010-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL.... 000061 in § 510.600(c) of this chapter. (c) Conditions of use in dogs—(1) Amount. For dogs weighing less than 30 lbs. instill 4 drops once daily into the ear canal. For dogs weighing 30 lbs. or more, instill...

  18. COMPARATIVE STUDY OF TOPICAL MOMETASONE FUROATE 0.1%, TOPICAL 0.03% TACROLIMUS, TOPICAL BASIC FIBROBLAST GROWTH FACTOR (bFGF IN CHILDHOOD VITILIGO

    Kavitha S. B

    2017-08-01

    Full Text Available BACKGROUND Vitiligo, the commonest of all pigmentary disorders, is an idiopathic, acquired cutaneous achromia, characterised by circumscribed, chalky white macules. It may also involve the pigment epithelium of the eyes, the inner ear and the leptomeninges. Although, vitiligo can begin at any age, it develops before the age of 20 years in 50% of the patients and before the age of 10 years in 25% of patients. MATERIALS AND METHODS The study was conducted for a period of one year with 6 months active intervention. A group of 60 consecutive children attending the outpatient Department of Dermatology were included in this study. The same patients were acting as controls. RESULTS Grade 4 response was seen in 12 cases (60% who were on mometasone (VV-20%, focal-30%, segmental-10%, in 10 cases (50% on tacrolimus (VV-20%, focal-30% and in 4 cases (20% on bFGF (focal. Lesions on the face and neck showed grade 4 response in 16 cases (mometasone-8, tacrolimus-6 and bFGF-2, extremities in 6 cases. On the whole grade, 4 response was observed more with mometasone (60% followed by tacrolimus (50%. Grade 3 response was observed with bFGF (30%. CONCLUSION Topical mometasone was very effective among the 3 drugs used in childhood vitiligo showing grade 4 repigmentation in all types of vitiligo except mucosal vitiligo. Tacrolimus proved almost as effective as mometasone to restore skin colour in lesions of vitiligo in children. Because it does not produce atrophy or other adverse effects, tacrolimus may be very useful for younger patients, and for sensitive areas of the skin such as eyelids, it should be considered in other skin disorders currently treated with topical steroids for prolonged periods. Topical basic fibroblast growth factor though less effective than mometasone and tacrolimus, but can be tried as initial therapy in resistant cases such as segmental vitiligo as initial therapy of small vitiligo patches when physicians may not like to initiate high risk

  19. Twelve-week efficacy and safety study of mometasone furoate/formoterol 200/10 microg and 400/10 microg combination treatments in patients with persistent asthma previously receiving high-dose inhaled corticosteroids

    Weinstein, Steven F; Corren, Jonathan; Murphy, Kevin

    2010-01-01

    A significant unmet medical need exists in patients with uncontrolled asthma. The purpose of this study was to evaluate the efficacy and safety of mometasone furoate/formoterol (MF/F) 400/10 microg versus MF 400 microg administered twice-daily (b.i.d.) via metered-dose inhaler in patients...... with asthma uncontrolled on high-dose inhaled corticosteroids (ICS). In a 12-week, randomized, multicenter, double-blind, parallel-group study, patients (>or=12 years of age) were randomized to MF/F 200/10 microg, MF/F 400/10 microg, or MF 400 microg, b.i.d. after a 2- to 3-week open-label run in with MF 400...... microg b.i.d. The primary end point was mean change in area under the curve from 0 to 12 hours in forced expiratory volume in 1 second (FEV(1) AUC(0-12h)) from baseline to week 12 for MF/F 400/10 microg versus MF 400 microg. Effects of MF/F on asthma control and symptoms were evaluated and adverse events...

  20. Efficacy and safety of a fixed-dose combination of mometasone furoate and formoterol fumarate in subjects with moderate to very severe COPD: results from a 52-week Phase III trial

    Tashkin DP

    2012-02-01

    Full Text Available Donald P Tashkin1, Dennis E Doherty2, Edward Kerwin3, Carlos E Matiz-Bueno4, Barbara Knorr5, Tulin Shekar5, Sibabrata Banerjee5, Heribert Staudinger51David Geffen School of Medicine at UCLA, Los Angeles, CA, 2Division of Pulmonary, Critical Care, and Sleep Medicine, University of Kentucky, Lexington, KY, 3Clinical Research Institute of Southern Oregon, Medford, OR USA; 4Fundación Salud Bosque, Bogota, Colombia; 5Merck Sharp & Dohme Corp, Whitehouse Station, NJ USABackground: A clinical trial of mometasone furoate/formoterol fumarate (MF/F administered via a metered-dose inhaler in subjects with moderate to very severe chronic obstructive pulmonary disease (COPD investigated the efficacy and safety of a fixed-dose combination of MF/F.Methods: This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1055; ≥40 years were current or ex-smokers randomized to twice-daily treatment with inhaled MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. The coprimary endpoints of the trial were mean changes from baseline in forced expiratory volume in 1 second (FEV1 over 0–12 hours (AUC0–12 FEV1 with MF/F versus MF, and in morning predose FEV1 with MF/F versus F. Key secondary endpoints were quality of life (Saint George’s Respiratory Questionnaire [SGRQ], symptom-free nights, and partly stable COPD at 26 weeks, as well as time to first COPD exacerbation.Results: Significant improvements in FEV1 AUC0–12 occurred at endpoint with MF/F 400/10 and MF/F 200/10 versus MF 400 (P ≤ 0.007. Significant bronchodilation occurred in 5 minutes with MF/F, and serial spirometry demonstrated sustained FEV1 improvements with MF/F over the treatment period. Significant improvements in morning predose FEV1 occurred with both MF/F doses, and these effects were further investigated by excluding results for subjects whose morning FEV1 data were collected >2 days after the last

  1. Fluticasone furoate: A new intranasal corticosteroid

    R Kumar

    2012-01-01

    Full Text Available Intranasal corticosteroids are recommended as one of the first-line therapies for the treatment of allergic rhinitis (AR, especially when associated with nasal congestion and recurrent symptoms. Fluticasone furoate is a novel enhanced-affinity glucocorticoid for the treatment of AR approved by the Food and Drug Administration in 2007 and recently introduced in India. Fluticasone furoate nasal spray is indicated for the treatment of the symptoms of seasonal and perennial AR in patients aged two years and older. This review summarizes the clinical data on fluticasone furoate nasal spray and discusses its role in the management of AR. Important attributes of fluticasone furoate include low systemic bioavailability (<0.5%, 24-h symptom relief with once-daily dosing, comprehensive coverage of both nasal and ocular symptoms, safety and tolerability with daily use, and availability in a side-actuated device that makes medication delivery simple and consistent. With these properties, fluticasone furoate nasal spray has the potential to enhance patient satisfaction and compliance, thus making it a good choice amongst available intranasal steroids.

  2. Effects of mometasone, fluticasone, and montelukast on bone mineral density in adults with asthma

    Maspero, Jorge; Backer, Vibeke; Yao, Ruji

    2014-01-01

    BACKGROUND: Associations of inhaled corticosteroids (ICS) with bone mineral density (BMD) loss have not been characterized consistently. OBJECTIVE: This randomized, double-blind study assessed effects of mometasone furoate (MF) administered via dry powder inhaler on BMD of patients with persisten...

  3. Extended Efficacy of Once-Daily Atomoxetine in ADHD

    J Gordon Millichap

    2004-07-01

    Full Text Available The efficacy of atomoxetine administered once daily (final dose 1.3 +/- 0.3 mg/kg; mean 44.5 mg per day; range 10-80 mg per day in the morning was assessed throughout the day, including evening and early morning, in a total of 197 children, 6 to 12 years of age (71% male, diagnosed with attention-deficit/hyperactivity disorder (ADHD (69% had combined subtype ADHD, and 35% had comorbid oppositional defiant disorder.

  4. Potential benefit of dolutegravir once daily: efficacy and safety

    Fantauzzi A

    2013-02-01

    Full Text Available Alessandra Fantauzzi,1 Ombretta Turriziani,2 Ivano Mezzaroma11Department of Clinical Medicine, 2Department of Molecular Medicine, Sapienza, University of Rome, Rome, ItalyAbstract: The viral integrase enzyme has recently emerged as a primary alternative target to block HIV-1 replication, and integrase inhibitors are considered a pivotal new class of antiretroviral drugs. Dolutegravir is an investigational next-generation integrase inhibitor showing some novel and intriguing characteristics, ie, it has a favorable pharmacokinetic profile with a prolonged intracellular half-life, rendering feasible once-daily dosing without the need for ritonavir boosting and without regard to meals. Moreover, dolutegravir is primarily metabolized via uridine diphosphate glucuronosyltranferase 1A1, with a minor component of the cytochrome P450 3A4 isoform, thereby limiting drug–drug interactions. Furthermore, its metabolic profile enables coadministration with most of the other available antiretroviral agents without dose adjustment. Recent findings also demonstrate that dolutegravir has significant activity against HIV-1 isolates with resistance mutations associated with raltegravir and/or elvitegravir. The attributes of once-daily administration and the potential to treat integrase inhibitor-resistant viruses make dolutegravir an interesting and promising investigational drug. In this review, the main concerns about the efficacy and safety of dolutegravir as well as its resistance profile are explored by analysis of currently available data from preclinical and clinical studies.Keywords: antiretroviral drugs, HIV-1 integrase, integrase inhibitors, dolutegravir, once daily

  5. Once-Daily Radiation Therapy for Inflammatory Breast Cancer

    Brown, Lindsay; Harmsen, William; Blanchard, Miran; Goetz, Matthew; Jakub, James; Mutter, Robert; Petersen, Ivy; Rooney, Jessica; Stauder, Michael; Yan, Elizabeth; Laack, Nadia

    2014-01-01

    Purpose: Inflammatory breast cancer (IBC) is a rare and aggressive breast cancer variant treated with multimodality therapy. A variety of approaches intended to escalate the intensity and efficacy of radiation therapy have been reported, including twice-daily radiation therapy, dose escalation, and aggressive use of bolus. Herein, we examine our outcomes for patients treated with once-daily radiation therapy with aggressive bolus utilization, focusing on treatment technique. Methods and Materials: A retrospective review of patients with nonmetastatic IBC treated from January 1, 2000, through December 31, 2010, was performed. Locoregional control (LRC), disease-free survival (DFS), overall survival (OS) and predictors thereof were assessed. Results: Fifty-two women with IBC were identified, 49 (94%) of whom were treated with neoadjuvant chemotherapy. All underwent mastectomy followed by adjuvant radiation therapy. Radiation was delivered in once-daily fractions of 1.8 to 2.25 Gy (median, 2 Gy). Patients were typically treated with daily 1-cm bolus throughout treatment, and 33 (63%) received a subsequent boost to the mastectomy scar. Five-year Kaplan Meier survival estimates for LRC, DFS, and OS were 81%, 56%, and 64%, respectively. Locoregional recurrence was associated with poorer OS (P<.001; hazard ratio [HR], 4.1). Extracapsular extension was associated with worse LRC (P=.02), DFS (P=.007), and OS (P=.002). Age greater than 50 years was associated with better DFS (P=.03). Pathologic complete response was associated with a trend toward improved LRC (P=.06). Conclusions: Once-daily radiation therapy with aggressive use of bolus for IBC results in outcomes consistent with previous reports using various intensified radiation therapy regimens. LRC remains a challenge despite modern systemic therapy. Extracapsular extension, age ≤50 years, and lack of complete response to chemotherapy appear to be associated with worse outcomes. Novel strategies are needed in IBC

  6. Study Of Topical Anti-Inflammatory Potency And Clinical Efficacy Of Formulations Of Mometasone And Betamethasone By Cutaneous Blood Flow Measurements In Psoriatic Patients Using Laser Doppler Velocimetry

    Mulekar S. V

    1997-01-01

    Full Text Available Laser Doppier Velocimetry (LDV was used to measure cutaneous blood flow (CBF in psoriatic skin lesions to assess the effect of once daily application of Mometasone furoate (MF in a base claimed to possess a “reservoir” effect, as against Betamethasone-17-valarate (BV in a conventional cream base, applied twice daily, for 4 weeks. Bilaterally symmetrical active lesions were studied in 10 psoriatics, at baseline and at the end of 2 and 4 weeks’ treatment. The formulations were also evaluated for topical anti-inflammatory potency in terms of their ability to inhibit the Post-Ischaemic-Reactive-Hyperaemic-Response (PIRHR induced on normal uninvolved skin treated under occlusion. The lesions were also assessed subjectively for clinical Psoriatic Hyperaemia Index (PHI = CBF on lesions/CBF on uninvolved skin: 8.42 + 1.74 & 10.13 + 1.70 correlating with high CPI (9 + 0.50 & 9.1 + 0.51. During treatment with MF or BV, the lesions resolved rapidly, with a concomitant decrease in PHI and CPI (Week 2 : PHI = 3.40 + 0.46 & 5.19 + 1.65, CPI = 4.15 + 0.86& 5.20 + 0.87 and Week 4 : PHI = 1.99 + 0.23 & 2.81 + 0.74 CPI = 2.00 + 0.50 & 2.88 + 0.72 respectively. The two formulations Inhibited PIRHR to same extent (auc/min: Control = 1871 + 399.22, MF = 536.11 + 153.34 & BV = 567.5 + 110.76, indicating equal potency. The results show that pharmaceutical factor such as vehicle can significantly influence the clinical efficacy of corticoids.

  7. Detemir as a once-daily basal insulin in type 2 diabetes

    Nelson SE

    2011-08-01

    Full Text Available Scott E NelsonCleveland Family Medicine, Cleveland, Mississippi, USABackground: Insulin detemir, a long-acting basal insulin analog, is labeled for once-daily or twice-daily dosing in patients with type 1 (T1DM or type 2 (T2DM diabetes mellitus. Protocols for some earlier clinical studies of detemir evaluated twice-daily dosing, which may have generated the misperception that detemir should be prescribed twice daily for most patients. This review examines pharmacokinetic and pharmacodynamic (PK/PD, observational, and controlled studies that have evaluated once-daily and twice-daily detemir in patients with T2DM to determine the efficacy and safety of once-daily dosing.Methods: PubMed was searched using the keywords “detemir,” “once daily,” “twice daily,” and “type 2 diabetes” with the limits of clinical trial, human, and English.Results: Detemir has a relatively flat time–action profile and duration of action of up to 24 hours for patients with T2DM. Once-daily dosing is the most commonly used detemir regimen reported in observational studies, and controlled clinical studies indicate that once-daily dosing controls glycosylated hemoglobin when detemir is administered alone or in combination with a prandial insulin or oral antidiabetes drugs. In comparative clinical trials, detemir had a similar time–action profile and duration of action to another long-acting insulin analog, glargine, with less within-subject variability. Once-daily detemir was associated with no weight gain or less weight gain than comparator regimens. For patients who had not achieved glycemic control with a basal dose of once-daily detemir, adding a prandial insulin provided better glycemic control, less postprandial hypoglycemia, and a lower total daily dose of detemir than twice-daily detemir. Involvement of a multidisciplinary team and the use of a holistic approach for the treatment of T2DM patients are recommended to achieve and maintain the best

  8. Cerebrospinal fluid abacavir concentrations in HIV-positive patients following once-daily administration.

    Calcagno, A; Pinnetti, C; De Nicolò, A; Scarvaglieri, E; Gisslen, M; Tempestilli, M; D'Avolio, A; Fedele, V; Di Perri, G; Antinori, A; Bonora, S

    2018-06-01

    Abacavir is a widely used nucleotide reverse transcriptase inhibitor, for which cerebrospinal fluid (CSF) exposure has been previously assessed in twice-daily recipients. We studied abacavir CSF concentrations in 61 and nine HIV-positive patients taking abacavir once daily and twice daily, respectively. Patients on once-daily abacavir had higher plasma and CSF concentrations (96 vs. 22 ng ml -1 , P = 0.038 and 123 vs. 49 ng ml -1 , P = 0.038) but similar CSF-to-plasma ratios (0.8 vs. 0.5, P = 0.500). CSF abacavir concentrations were adequate in patients receiving once-daily treatment. © 2018 The British Pharmacological Society.

  9. Efficacy and safety of rosuvastatin every other day compared with once daily in patients with hypercholesterolemia.

    Wongwiwatthananukit, Supakit; Sansanayudh, Nakarin; Dhummauppakorn, Rawadee; Kitiyadisai, Chutiporn

    2006-11-01

    Although most patients with hypercholesterolemia require life-long therapy with statins, these drugs are underused due to high costs. Every-other-day therapy could be one strategy to resolve this problem. To compare the efficacy and safety of rosuvastatin 10 mg administered every other day versus once daily. An 8 week, randomized, open-label, parallel trial was conducted at the outpatient department of Phramongkutklao Hospital in Bangkok, Thailand. Eighty patients with primary hypercholesterolemia were equally randomized to receive rosuvastatin 10 mg once daily or every other day; 76 patients completed the study. Laboratory data were assessed at baseline and at the end of the study. Low-density lipoprotein cholesterol (LDL-C) levels were reduced by 48% and 39% in the once-daily and every-other-day groups, respectively (p = 0.011). The percentage of patients who achieved LDL-C goals according to National Cholesterol Education Program-Adult Treatment Panel III guidelines was not significantly different between the once-daily (85%) and every-other-day (70%) groups (p = 0.180). In addition, both regimens were well tolerated, with no patient developing an elevation of more than 3 times baseline levels of aspartate aminotransferase or alanine aminotransferase or 10 times that of creatine kinase. As expected, the monthly cost per percent LDL-C reduction of the once-daily (0.72 dollars) regimen was about 38% higher than that of the every-other-day (0.44 dollars) regimen. Every-other-day dosing of rosuvastatin may be an alternative regimen for cost savings, without a major decrease in therapeutic benefit or increase in adverse events, in patients with hypercholesterolemia. The number of patients achieving their LDL-C goal using the every-other-day regimen is comparable with the number using the once-daily regimen, especially in the low-risk patient category.

  10. Efficacy and safety of once daily low molecular weight heparin (tinzaparin sodium) in high risk pregnancy.

    Ní Ainle, Fionnuala

    2008-10-01

    Low molecular weight heparin (LMWH) is widely regarded as the anticoagulant treatment of choice for the prevention and treatment of venous thromboembolism during pregnancy. However, previous studies have demonstrated that the pharmacokinetic profiles of LMWH vary significantly with increasing gestation. Consequently, it remains unclear whether LMWH regimens recommended for use in nonpregnant individuals can be safely extrapolated to pregnant women. The aims of this study were to assess the safety and the efficacy of tinzaparin sodium (Innohep) administered only once daily during pregnancy. A systematic retrospective review identified a cohort of 37 high-risk pregnancies which had been managed using tinzaparin 175 IU\\/kg once daily. In 26 cases, the index pregnancy had been complicated by development of an acute venous thromboembolism (17 deep vein thrombosis and nine pulmonary embolism). For each individual, case notes were examined and data extracted using a predetermined questionnaire. No episodes of recurrent venous thromboembolism were identified amongst this cohort of pregnancies managed using once daily LMWH administration. However, two unusual thrombotic complications were observed, including a parietal infarct in one patient, and a postpartum cerebral venous thrombosis in another. Once daily tinzaparin was well tolerated, with no cases of heparin-induced thrombocytopaenia, symptomatic osteoporosis, or foetal malformations. Tinzaparin dose modification based upon peak anti-Xa levels occurred in 45% of the cases examined. The present study is the largest study to have examined the clinical efficacy of once daily LMWH for use in pregnant women at high risk of venous thromboembolism. Our data support the safety and efficacy of antenatal tinzaparin at a dose of 175 IU\\/kg. In order to determine whether this once daily regimen provides equivalent (or indeed greater) thromboprophylaxis to twice daily LMWH regimens during pregnancy will require highly powered

  11. Once-daily use of inhaled corticosteroids: A new regimen in the treatment of persistent asthma

    Jeffrey Leflein

    2000-01-01

    Strict patient adherence with prescribed anti-inflammatory medication is crucial for obtaining optimal therapeutic benefit for patients with asthma. Despite the proven effectiveness of inhaled corticosteroids, patient adherence to prescribed therapy is often low, resulting in increased patient morbidity. Complex dosing regimens contribute greatly to patient non-adherence. Thus, new once-daily regimens of inhaled corticosteroid treatment have been introduced as means to improve patient adherence and provide optimal therapeutic benefit. In the present review, the complex inflammatory and remodeling processes in asthma and their contributions to the clinical manifestations of the disease will be discussed. Currently available, once-daily inhaled corticosteroid treatment options and the advantages of these therapeutic options in the treatment of persistent asthma also will be discussed.

  12. The antianginal efficacy and tolerability of controlled-release metoprolol once daily

    Egstrup, K; Gundersen, T; Härkönen, R

    1988-01-01

    In a randomized, double-blind, cross-over study treatment with a new controlled-release (CR) preparation of metoprolol, given once daily, was compared with treatment with conventional metoprolol tablets, given twice daily, in 115 patients with stable effort angina pectoris. The patients were...... questionnaire. When all patients were analysed together there were no differences in antianginal efficacy between the two treatment regimens. However, when the group taking 200 mg daily was analysed separately better exercise tolerance was found during metoprolol CR therapy, as measured by onset of chest pain...... and ST-segment change, compared with conventional metoprolol therapy. The two formulations were well tolerated. When given once daily in a total daily dose of 100 mg, the CR preparation induced less adverse effects than the conventional tablets, 50 mg twice daily. It was concluded that the new metoprolol...

  13. Update on the clinical utility of once-daily tacrolimus in the management of transplantation

    Revollo J

    2015-05-01

    Full Text Available Jane Revollo Department of Pharmacy, Jackson Memorial Hospital, University of Miami Leonard M Miller School of Medicine Miami, FL, USAThe review by Posadas Salas and Srinivas of the clinical utility of once-daily tacrolimus formulations in the management of transplant patients1 was timely and relevant. It is worth noting, however, the data were presented in a way that overlooked several key differences between two distinct once-daily tacrolimus formulations. These formulations differ in bioavailability, Cmax, Tmax, dose required to achieve target trough levels, and time to reach target trough. The specific formulation and dosing information of one product was detailed in this review (described as modified release 4 [MR-4]; Astagraf®, Astellas Pharma Inc., Tokyo, Japan, but no formulation or dosing details were provided for a very different once-daily tacrolimus formulation (LCP-Tacro™; Veloxis Pharmaceuticals A/S, Hørsholm, Denmark for which a thorough review was recently published.2 The latter product is currently approved in Europe and under review by the US Food and Drug Administration in the US. In presenting data in this review, the authors did not identify which product was investigated in each of the studies discussed. This could easily lead to misinterpretation of results or erroneous conclusions, ie, that both once-daily formulations are the same. In fact, a careful parsing of the data clearly demonstrates that they are not equivalent. Misunderstanding of this point could have a potentially serious impact on appropriate dosing, safety, and patient management in the post-transplant setting. Differentiation between the two products is needed to clarify what appear to be conflicting results of the studies presented in this review.View original paper by Posadas Salas and Srinivas

  14. Once daily, extended release ciprofloxacin for complicated urinary tract infections and acute uncomplicated pyelonephritis.

    Talan, David A; Klimberg, Ira W; Nicolle, Lindsay E; Song, James; Kowalsky, Steven F; Church, Deborah A

    2004-02-01

    We assessed the efficacy and safety of 1,000 mg extended release ciprofloxacin orally once daily vs conventional 500 mg ciprofloxacin orally twice daily, each for 7 to 14 days, in patients with a complicated urinary tract infection (cUTI) or acute uncomplicated pyelonephritis (AUP). In this prospective, randomized, double-blind, North American multicenter clinical trial adults were stratified based on clinical presentation of cUTI or AUP and randomized to extended release ciprofloxacin or ciprofloxacin twice daily. Efficacy valid patients had positive pretherapy urine cultures (105 or greater cFU/ml) and pyuria within 48 hours of study entry. Bacteriological and clinical outcomes were assessed at the test of cure visit (5 to 11 days after therapy) and the late followup visit (28 to 42 days after therapy). The intent to treat population comprised 1,035 patients (extended release ciprofloxacin in 517 and twice daily in 518), of whom 435 were efficacy valid (cUTI in 343 and AUP in 92). For efficacy valid patients (cUTI and AUP combined) bacteriological eradication rates at test of cure were 89% (183 of 206) vs 85% (195 of 229) (95% CI -2.4%, 10.3%) and clinical cure rates were 97% (198 of 205) vs 94% (211 of 225) (95% CI -1.2%, 6.9%) for extended release vs twice daily ciprofloxacin. Late followup outcomes were consistent with test of cure findings. Eradication rates for Escherichia coli, which accounted for 58% of pathogens, were 97% or greater per group. Drug related adverse event rates were similar for extended release and twice daily ciprofloxacin (13% and 14%, respectively). Extended release ciprofloxacin at a dose of 1,000 mg once daily was as safe and effective as conventional treatment with 500 mg ciprofloxacin twice daily, each given orally for 7 to 14 days in adults with cUTI or AUP. It provides a convenient, once daily, empirical treatment option.

  15. Effect of sprint training: training once daily versus twice every second day.

    Ijichi, Toshiaki; Hasegawa, Yuta; Morishima, Takuma; Kurihara, Toshiyuki; Hamaoka, Takafumi; Goto, Kazushige

    2015-01-01

    This study compared training adaptations between once daily (SINGLE) and twice every second day (REPEATED) sprint training, with same number of training sessions. Twenty physically active males (20.9 ± 1.3 yr) were assigned randomly to the SINGLE (n = 10) or REPEATED (n = 10) group. The SINGLE group trained once per day (5 days per week) for 4 weeks (20 sessions in total). The REPEATED group conducted two consecutive training sessions on the same day, separated by a rest period of 1 h (2-3 days per week) for 4 weeks (20 sessions in total). Each training session consisted of three consecutive 30-s maximal pedalling sets with a 10-min rest between sets. Before and after the training period, the power output during two bouts of 30-s maximal pedalling, exercise duration during submaximal pedalling and resting muscle phosphocreatine (PCr) levels were evaluated. Both groups showed significant increases in peak and mean power output during the two 30-s bouts of maximal pedalling after the training period (P every second day improved OBLA during endurance exercise more than the same training once daily.

  16. Effects of Tadalafil 5 mg Dosed Once Daily in Men with Premature Ejaculation.

    Ozcan, Levent; Polat, Emre Can; Onen, Efe; Kocaaslan, Ramazan; Otunctemur, Alper; Cekmen, Mustafa; Eraldemir, Ceyla; Ozbek, Emin

    2017-01-01

    In this study, we evaluated the effect of 5 mg tadalafil once daily in men with premature ejaculation (PE). Thirty married men with lifelong PE and 30 healthy men as control group were included in this study. All the patients received 5 mg tadalafil once a day for a month. The international index of erectile function questionnaire and intravaginal ejaculatory latency times (IELTs) and PE profile were recorded before and after treatment. Plasma samples were collected before and after treatment. The mean baseline IELTs was 40.8 ± 8.1 s in the PE group and 196.5 ± 26.2 s in the control group. After treatment in the PE group, the mean IELTs values showed a statistically significant improvement from the baseline values. At the end of 4 weeks, in the PE group, the mean IELT values showed a statistically significant improvement from the baseline values. Baseline serum nitric oxide (NO) levels were 27.3 ± 1.7 in the PE group and in the 31.1 ± 1.4 healthy control groups. After treatment, NO levels were increased from baseline. We consider that 5 mg tadalafil once daily is safety and effective for the treatment of PE. © 2016 S. Karger AG, Basel.

  17. Efficacy and safety of terbinafine 500 mg once daily in patients with dermatophytosis

    P Ravindra Babu

    2017-01-01

    Full Text Available Introduction: Dermatophytosis are the most common fungal infections globally. Terbinafine is considered to have good potency against dermatophytes, but resistance to terbinafine is on the rise. Objective: The objective of this study was to evaluate the efficacy and safety of terbinafine 500 mg given once daily in treatment of patients with superficial dermatophytosis. Materials and Methods: It was a retrospective questionnaire-based survey. Each doctor was given survey questionnaire booklet containing survey forms. Clinical response was graded according to the improvement in the affected lesion. Mycological cure was defined as negative microscopy under potassium hydroxide examination and a negative culture in Sabouraud's dextrose agar. Patients were divided into three groups depending on the duration of therapy, Group A – terbinafine 500 mg for 2 weeks, Group B – terbinafine 500 mg for 4 weeks, and Group C – terbinafine 500 mg for 6 weeks. Results: Total 50 doctors completed the survey involving 440 patients. In Group A, out of 194 patients, 87% (n = 169 patients showed very good response. In Group B, out of 211 patients, 92% (n = 194 of the patients showed very good response with >75% improvement in their lesion. In Group C, out of 35 patients, 80% (n = 30 patients showed very good response. Adverse drug reactions of mild to moderate intensity related to terbinafine were seen in 57 patients. Conclusion: Our survey indicates that terbinafine in a dose of 500 mg given once daily was efficacious and safe in the treatment of patients with dermatophytosis.

  18. Efficacy and Safety of Terbinafine 500 mg Once Daily in Patients with Dermatophytosis.

    Babu, P Ravindra; Pravin, A J S; Deshmukh, Gaurav; Dhoot, Dhiraj; Samant, Aniket; Kotak, Bhavesh

    2017-01-01

    Dermatophytosis are the most common fungal infections globally. Terbinafine is considered to have good potency against dermatophytes, but resistance to terbinafine is on the rise. The objective of this study was to evaluate the efficacy and safety of terbinafine 500 mg given once daily in treatment of patients with superficial dermatophytosis. It was a retrospective questionnaire-based survey. Each doctor was given survey questionnaire booklet containing survey forms. Clinical response was graded according to the improvement in the affected lesion. Mycological cure was defined as negative microscopy under potassium hydroxide examination and a negative culture in Sabouraud's dextrose agar. Patients were divided into three groups depending on the duration of therapy, Group A - terbinafine 500 mg for 2 weeks, Group B - terbinafine 500 mg for 4 weeks, and Group C - terbinafine 500 mg for 6 weeks. Total 50 doctors completed the survey involving 440 patients. In Group A, out of 194 patients, 87% ( n = 169) patients showed very good response. In Group B, out of 211 patients, 92% ( n = 194) of the patients showed very good response with >75% improvement in their lesion. In Group C, out of 35 patients, 80% ( n = 30) patients showed very good response. Adverse drug reactions of mild to moderate intensity related to terbinafine were seen in 57 patients. Our survey indicates that terbinafine in a dose of 500 mg given once daily was efficacious and safe in the treatment of patients with dermatophytosis.

  19. [Effectiveness of new, once-daily 5-aminosalicylic acid in the treatment of ulcerative colitis].

    Lakatos, Péter László; Lakatos, László

    2009-03-01

    5-aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents is commercially available, including azo-bond pro-drugs such as sulfasalazine, olsalazine and balsalazide, and delayed- and controlled-release forms of mesalazine. In addition, the effectiveness of oral therapy relies on good compliance, which may be adversely affected by frequent daily dosing and a large number of tablets. Furthermore, poor adherence has been shown to be an important barrier to successful management of patients with UC. Recently, new, once-daily formulations of mesalazine including the unique multi-matrix delivery system and mesalazine granules were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC, with a good safety profile comparable to that of other oral mesalazine formulations. In addition, they offer the advantage of low pill burden and may contribute to increased long-term compliance and treatment success in clinical practice and might potentially further contribute to a decline in the risk for UC-associated colon cancers. In this systematic review, the authors summarize the available literature on the short- and medium-term efficacy and safety of the new once-daily mesalazine formulations.

  20. Onychomycosis of Toenails and Post-hoc Analyses with Efinaconazole 10% Solution Once-daily Treatment

    2016-01-01

    Topical treatment for toenail onychomycosis has been fraught with a long-standing reputation of poor efficaey, primarily due to physical properties of the nail unit that impede drug penetration. Newer topical agents have been formulated as Solution, which appear to provide better therapeutic response in properly selected patients. It is important to recognize the impact the effects that mitigating and concomitant factors can have on efficaey. These factors include disease severity, gender, presence of tinea pedis, and diabetes. This article reviews results achieved in Phase 3 pivotal studies with topical efinaconazole 10% Solution applied once daily for 48 weeks with a focus on how the aforementioned factors influenced therapeutic outcomes. It is important for clinicians treating patients for onychomycosis to evaluate severity, treat concomitant tinea pedis, address control of diabetes if present by encouraging involvement of the patient’s primary care physician, and consider longer treatment courses when clinically relevant. PMID:27047631

  1. Liraglutide: a once-daily GLP-1 analogue for the treatment of type 2 diabetes mellitus

    Vilsbøll, Tina

    2007-01-01

    properties that are suitable for once-daily dosing. Liraglutide has demonstrated lasting improvement of HbA(1c )levels, weight reduction and improved beta-cell function in patients with Type 2 diabetes mellitus. Liraglutide is well tolerated; the adverse events that are most frequently reported being...... transient nausea and diarrhoea. This article reviews the mechanisms of action and efficacy of liraglutide for the treatment of Type 2 diabetes mellitus. This agent is presently in Phase III clinical development.......The incretin hormones are intestinal peptides that enhance insulin secretion following ingestion of nutrients. Liraglutide is a glucagon-like peptide-1 receptor analogue, which is obtained by derivatising glucagon-like peptide-1 with a fatty acid, providing a compound with pharmacokinetic...

  2. Liraglutide: a once-daily GLP-1 analogue for the treatment of type 2 diabetes mellitus

    Vilsbøll, Tina

    2007-01-01

    The incretin hormones are intestinal peptides that enhance insulin secretion following ingestion of nutrients. Liraglutide is a glucagon-like peptide-1 receptor analogue, which is obtained by derivatising glucagon-like peptide-1 with a fatty acid, providing a compound with pharmacokinetic propert...... transient nausea and diarrhoea. This article reviews the mechanisms of action and efficacy of liraglutide for the treatment of Type 2 diabetes mellitus. This agent is presently in Phase III clinical development....... properties that are suitable for once-daily dosing. Liraglutide has demonstrated lasting improvement of HbA(1c )levels, weight reduction and improved beta-cell function in patients with Type 2 diabetes mellitus. Liraglutide is well tolerated; the adverse events that are most frequently reported being...

  3. Gabapentin for once-daily treatment of post-herpetic neuralgia: a review

    Beal B

    2012-07-01

    Full Text Available Benjamin Beal,1 Tobias Moeller-Bertram,1,2 Jan M Schilling,1 Mark S Wallace11Division of Pain Medicine, Department of Anesthesiology, University of California, 2VA San Diego Healthcare System, San Diego, CA, USAAbstract: Post-herpetic neuralgia is a neuropathic pain syndrome resulting from an insult to the peripheral and central nervous systems caused by the varicella zoster virus. Spontaneous pain may result in the persistent sensation of burning, tingling, or aching and may be associated with thermally or mechanically provoked pain, resulting in hyperalgesia or allodynia. The majority of cases occur in patients over the age of 50 years. Gabapentin is a structural analog of gamma aminobutyric acid that binds to the α2-δ site of voltage-dependent calcium channels and modulates the influx of calcium, with a resulting reduction in excitatory neurotransmitter release. Gabapentin is effective in reducing neuropathic pain due to post-herpetic neuralgia when given at least three times per day, due to its short half-life, resulting in demonstrable fluctuations in plasma levels. Gabapentin has dose-limiting side effects that prevent some patients from achieving therapeutic plasma levels, such as somnolence (27.4%, dizziness (23.9%, and ataxia (7.1%. Gralise™ is a once-daily extended-release formulation of gabapentin that has been developed using AcuForm™ technology. AcuForm is a polymer-based drug delivery system that retains the tablet in the stomach and upper gastrointestinal tract for a sustained period of time. Once-daily dosing has been shown to provide comparable drug exposure with an identical daily dose of the immediate-release formulation when administered three times daily. Participants given Gralise 1800 mg daily had a statistically significant reduction in average daily pain intensity scores compared with placebo, reduced sleep interference due to pain, and a greater percent of participants reporting being much or very much improved on

  4. Efficacy and safety of once-daily aclidinium in chronic obstructive pulmonary disease

    Bateman Eric D

    2011-04-01

    Full Text Available Abstract Background The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD. Methods In two double-blind, 52-week studies, ACCLAIM/COPD I (n = 843 and II (n = 804, patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV1/forced vital capacity ratio of ≤70% and FEV1 1 at 12 and 28 weeks. Secondary endpoints were health status measured by St George's Respiratory Questionnaire (SGRQ and time to first moderate or severe COPD exacerbation. Results At 12 and 28 weeks, aclidinium improved trough FEV1 versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p Conclusion Aclidinium is effective and well tolerated in patients with moderate to severe COPD. Trial registration ClinicalTrials.gov: NCT00363896 (ACCLAIM/COPD I and NCT00358436 (ACCLAIM/COPD II.

  5. The emergence of oral tadalafil as a once-daily treatment for pulmonary arterial hypertension

    Jeremy A Falk

    2010-04-01

    Full Text Available Jeremy A Falk, Kiran J Philip, Ernst R SchwarzCedars Sinai Women’s Guild Lung Institute, Cedars Sinai Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA, USAAbstract: Pulmonary hypertension (PH is found in a vast array of diseases, with a minority representing pulmonary arterial hypertension (PAH. Idiopathic PAH or PAH in association with other disorders has been associated with poor survival, poor exercise tolerance, progressive symptoms of dyspnea, and decreased quality of life. Left untreated, patients with PAH typically have a progressive decline in function with high morbidity ultimately leading to death. Advances in medical therapy for PAH over the past decade have made significant inroads into improved function, quality of life, and even survival in this patient population. Three classes of pulmonary artery-specific vasodilators are currently available in the United States. They include prostanoids, endothelin receptor antagonists, and phosphodiesterase type 5 (PDE5 inhibitors. In May 2009, the FDA approved tadalafil, the first once-daily PDE5 inhibitor for PAH. This review will outline the currently available data on tadalafil and its effects in patients with PAH.Keywords: PDE-5 inhibition, pulmonary hypertension, tadalafil

  6. Tafluprost once daily for treatment of elevated intraocular pressure in patients with open-angle glaucoma

    Liu Y

    2012-12-01

    Full Text Available Yang Liu, Weiming MaoDepartment of Cell Biology and Anatomy, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TXAbstract: Glaucoma is a leading cause of visual loss worldwide. Current antiglaucoma therapy focuses on lowering intraocular pressure to a safe level. In recent years, prostaglandin analogs have become the first-line agents for treating open angle glaucoma. Tafluprost, which was first reported in 2003, is a novel prostaglandin analog, and has been shown to be a potent ocular hypotensive agent in a number of preclinical and clinical studies. Also, its unique preservative-free formulation helps to decrease preservative-associated ocular disorders and improve patient compliance. In this review, studies from 2003 to 2012 focusing on the structure, metabolism, efficacy, and safety of tafluprost are summarized. These studies suggested that application of tafluprost once daily is a safe and effective treatment for patients with open angle glaucoma.Keywords: tafluprost, prostaglandin analog, glaucoma, intraocular pressure, preservative-free formulation

  7. 21 CFR 524.1044h - Gentamicin sulfate, mometasone furoate, clotrimazole otic suspension.

    2010-04-01

    ... (Pseudomonas spp. [including P. aeruginosa], coagulase-positive staphylococci, Enterococcus faecalis, Proteus mirabilis, and beta-hemolytic streptococci). [66 FR 712, Jan. 4, 2001, as amended at 68 FR 15370, Mar. 31...

  8. 75 FR 16346 - Ophthalmic and Topical Dosage Form New Animal Drugs; Orbifloxacin, Mometasone Furoate Monohydrate...

    2010-04-01

    ... posaconazole for the treatment of otitis externa in dogs. DATES: This rule is effective April 1, 2010. FOR... posaconazole) Otic Suspension for the treatment of otitis externa in dogs associated with susceptible strains... statement is required. Under section 512(c)(2)(F)(ii) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C...

  9. A once-daily dose of tadalafil for erectile dysfunction: compliance and efficacy

    Samuel L Washington III

    2010-08-01

    Full Text Available Samuel L Washington III1, Alan W Shindel21School of Medicine, University of California at San Francisco, San Francisco, California, USA; 2Department of Urology, University of California at San Francisco, San Francisco, California, USAAbstract: Selective phosphodiesterase type 5 inhibitors (PDE5Is have revolutionized the ­treatment of erectile dysfunction (ED in men. As an on-demand treatment, PDE5Is have excellent efficacy and safety in the treatment of ED due to a broad spectrum of etiologies. Nevertheless, these drugs do have side-effect profiles that are troublesome to some patients, eg, headache, dyspepsia, myalgia, etc. Furthermore, many patients and their partners dislike the necessity of on-demand treatment for ED, citing a desire for greater spontaneity with sexual interactions. In 2008, approximately 10 years after the release of the first commercially available PDE5I, a paradigm shift in the management of ED occurred with the approval of once-daily dose of tadalafil by the US Food and Drug Administration for the management of ED. The prolonged half-life of tadalafil lends itself well to this dosing regimen and conveys the advantage of separating medication from sexual interactions; lower dose therapy also carries the theoretical benefit of lower incidence of side effects. In this study, we review the current state of the art with respect to this new management strategy for ED, highlighting published reports of the efficacy and tolerability of the daily dose tadalafil regimen.Keywords: PDE5 inhibitor, on-demand therapy, side effects, daily dosing

  10. Teriflunomide: a once-daily oral medication for the treatment of relapsing forms of multiple sclerosis.

    Miller, Aaron E

    2015-10-01

    The purpose was to summarize US prescribing information for teriflunomide in the treatment of patients with relapsing forms of multiple sclerosis (RMS), with reference to clinical efficacy and safety outcomes. In September 2012, the US Food and Drug Administration granted approval for the use of teriflunomide, 14 mg and 7 mg once daily, to treat RMS on the basis of the results of a Phase II study and the Phase III TEMSO (Teriflunomide Multiple Sclerosis Oral) trial. After recent updates to the prescribing information (October 2014), key findings from these and 2 other Phase III clinical trials, TOWER (Teriflunomide Oral in People With Relapsing Multiple Sclerosis) and TOPIC (Oral Teriflunomide for Patients with a First Clinical Episode Suggestive of Multiple Sclerosis), and practical considerations for physicians are summarized. Teriflunomide, 14 mg and 7 mg, significantly reduced mean number of unique active lesions on magnetic resonance imaging (MRI; P treatment was also associated with significant efficacy on MRI measures of disease activity in TEMSO; both doses significantly reduced total lesion volume and number of gadolinium-enhancing T1 lesions. TOPIC evaluated patients with a first clinical event consistent with acute demyelination and brain MRI lesions characteristic of multiple sclerosis. More patients were free of relapse in the teriflunomide 14-mg and 7-mg groups than in the placebo group (P treatment are recommended to assess potential safety issues. Women of childbearing potential must use effective contraception and, in the event of pregnancy, undergo an accelerated elimination procedure to reduce plasma concentrations of teriflunomide. Clinical evidence suggests that teriflunomide is an effective therapeutic choice for patients with RMS, both as an initial treatment and as an alternative for patients who may have experienced intolerance or inadequate response to a previous or current disease-modifying therapy. Copyright © 2015 The Authors

  11. Raltegravir once daily or twice daily in previously untreated patients with HIV-1: a randomised, active-controlled, phase 3 non-inferiority trial

    Eron, Joseph J.; Rockstroh, Jürgen K.; Reynes, Jacques; Andrade-Villanueva, Jaime; Ramalho-Madruga, Jose Valdez; Bekker, Linda-Gail; Young, Benjamin; Katlama, Christine; Gatell-Artigas, Jose Maria; Arribas, Jose R.; Nelson, Mark; Campbell, Havilland; Zhao, Jing; Rodgers, Anthony J.; Rizk, Matthew L.; Wenning, Larissa; Miller, Michael D.; Hazuda, Daria; DiNubile, Mark J.; Leavitt, Randi; Isaacs, Robin; Robertson, Michael N.; Sklar, Peter; Nguyen, Bach-Yen; Bloch, M. T.; Hoy, J.; Workman, C.; Madruga, J. V.; Souza, T.; Telles, F. Q.; Zajdenverg, R.; Angel, J.; Montaner, J. S.; Smith, G. H. R.; Trottier, B.; Tamara, J. R.; Velez, J. D.; Gerstoft, J.; Laursen, A. L.; Mathiesen, L.; Katlama, C.; Molina, J. M.; Raffi, F.; Reynes, J.; Yazdanpanah, Y.; Bogner, J. R.; Fatkenheuer, G.; Hartl, H.; Jaeger, H.; Geerlings, S. E.

    2011-01-01

    Twice-daily raltegravir with once-daily tenofovir-emtricitabine is an effective initial antiretroviral regimen for patients with HIV-1. On the basis of pharmacokinetic data suggesting efficacy of once-daily raltegravir and because adherence is often improved with once-daily dosing, we aimed to

  12. The steady-state pharmacokinetics of nevirapine during once daily and twice daily dosing in HIV-1-infected individuals

    van Heeswijk, R. P.; Veldkamp, A. I.; Mulder, J. W.; Meenhorst, P. L.; Wit, F. W.; Lange, J. M.; Danner, S. A.; Foudraine, N. A.; Kwakkelstein, M. O.; Reiss, P.; Beijnen, J. H.; Hoetelmans, R. M.

    2000-01-01

    OBJECTIVE: To investigate and to compare the steady-state plasma pharmacokinetics of nevirapine in a dosing regimen of 400 mg once daily versus 200 mg twice daily in HIV-1-infected individuals. DESIGN: Open-label, randomized, cross-over study. METHODS: Twenty HIV-1-infected individuals who already

  13. Once-daily dosing of saquinavir and low-dose ritonavir in HIV-1-infected individuals: a pharmacokinetic pilot study

    van Heeswijk, R. P.; Veldkamp, A. I.; Mulder, J. W.; Meenhorst, P. L.; Lange, J. M.; Beijnen, J. H.; Hoetelmans, R. M.

    2000-01-01

    To investigate the steady-state pharmacokinetics of a once-daily dosing regimen of saquinavir soft gelatin capsules in combination with a low dose of ritonavir in HIV-1-infected individuals. Open-label, multi-dose, pharmacokinetic pilot study. Seven HIV-1-infected individuals who were treated with

  14. Assessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus

    S Yu Vorotnikova

    2012-09-01

    Full Text Available Реферат по статье: Assessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus Juliana Levy, Roberta A Cobas, Marilia B Gomes. Diabetol Metab Syndr. 2010 Mar 18; 2:16.

  15. Treatment of streptococcal pharyngitis with once-daily compared with twice-daily amoxicillin: a noninferiority trial.

    Clegg, Herbert W; Ryan, Amy G; Dallas, Steven D; Kaplan, Edward L; Johnson, Dwight R; Norton, H James; Roddey, Oliver F; Martin, Edward S; Swetenburg, Raymond L; Koonce, Elizabeth W; Felkner, Mary M; Giftos, P Michael

    2006-09-01

    Two relatively small previous studies comparing once-daily amoxicillin with conventional therapy for group A streptococcal (GAS) pharyngitis reported similar rates of bacteriologic success for each treatment group. The purpose of this study was to further evaluate once-daily amoxicillin for GAS pharyngitis in a larger study. In a single pediatric practice, from October through May for 2 consecutive years (2001-2003), we recruited children 3 to 18 years of age who had symptoms and signs suggestive of GAS pharyngitis. Patients with a positive rapid test for GAS were stratified by weight (or=40 kg) and then randomly assigned to receive once-daily (750 mg or 1000 mg) or twice-daily (2 doses of 375 mg or 500 mg) amoxicillin for 10 days. We determined bacteriologic failure rates for GAS in the pharynx from subsequent swabs taken at 14 to 21 (visit 2) and 28 to 35 (visit 3) days after treatment initiation. We conducted a randomized, controlled, investigator-blinded, noninferiority trial to evaluate whether amoxicillin given once daily would have a bacteriologic failure rate no worse than that of amoxicillin given twice daily within a prespecified margin of 10%. GAS isolates were characterized to distinguish bacteriologic failures from new acquisitions. Adverse events were described and adherence was evaluated by review of returned daily logs and dosage bottles. Of 2139 potential study patients during the 2-year period, we enrolled 652 patients, 326 into each treatment group. Children in the 2 groups were comparable with respect to all demographic and clinical characteristics except that children <40 kg more often presented with rash in each treatment group. At visit 2, failure rates were 20.1% (59 of 294) for the once-daily group and 15.5% (46 of 296) for the twice-daily group (difference, 4.53%; 90% confidence interval [CI], -0.6 to 9.7). At visit 3, failure rates were 2.8% (6 of 216) for the once-daily group and 7.1% (16 of 225) for the twice-daily group (difference, -4

  16. A dose-finding, placebo-controlled study on extended-release felodipine once daily in treatment of hypertension.

    Cambell, L M; Ross, J R; Goves, J R; Lees, C T; McCullagh, A; Barnes, P; Timerick, S J; Richardson, P D

    1989-12-01

    Hypertensive patients received a beta-blocker plus placebo once daily for 4 weeks. If their diastolic blood pressure (DBP) was then 95-115 mm Hg, they were randomized to receive, in addition to the beta-blocker, placebo (n = 36), felodipine-extended release (ER) 10 mg (n = 36), or felodipine-ER 20 mg (n = 37) in a 4-week double-blind parallel-group trial. All medication was administered once daily and, when BP was measured 24 h after the last dose, felodipine-ER 10 mg reduced DBP by 14 +/- 9 mm Hg (mean +/- SD) from a mean of 103 mm Hg and felodipine-ER 20 mg reduced DBP by 18 +/- 9 mm Gg from 101 mm Hg. The reductions in DBP with both doses of felodipine were greater than reductions with placebo (5 +/- 8 mm Hg, from 102 mm Hg--both p less than 0.001). At the end of the study, 21% of patients receiving placebo had a DBP less than or equal to 90 mm Hg. In contrast, 69% of patients receiving felodipine-ER 10 mg and 82% receiving 20 mg attained this level. More than 90% of patients receiving 10 mg felodipine-ER once daily had a reduction in DBP greater than 5 mm Hg 24 h postdose. Felodipine-ER was well tolerated. Felodipine-ER once daily is an effective antihypertensive drug for patients who require therapy in addition to a beta-blocker; the tolerability in this study was good, and a starting dose greater than 10 mg once daily is not indicated.

  17. Fluticasone furoate and vilanterol inhalation powder for the treatment of chronic obstructive pulmonary disease.

    Matera, Maria Gabriella; Capuano, Annalisa; Cazzola, Mario

    2015-02-01

    Fluticasone furoate/vilanterol (FF/VI) is a novel inhaled corticosteroid/long-acting β₂-agonist (ICS/LABA) fixed dose combination that, by simplifying the dosing schedule, allows, for the first time in a member of the ICS/LABA class, a shift from twice-daily to once-daily treatment. FF/VI is delivered via a novel, single-step activation, multi-dose dry powder inhaler for oral inhalation, Ellipta. Regrettably, there are no head-to-head trials that have shown superiority in the safety or efficacy of FF versus other ICSs, but evidence shows that VI has a quicker onset of effect versus salmeterol. However, the clinical utility of this effect in a maintenance medication is still questionable. Furthermore, benefits of FF/VI over twice-daily ICS/LABA comparator have not been shown yet and, in addition, its adverse event profile is generally consistent with the known class effects of an ICS/LABA fixed dose combination. In particular, there is an increase in the risk of pneumonia among patients treated with FF/VI relative to VI, mainly among those who benefit most from FF/VI. Nevertheless, the interesting pharmacological profiles of both FF and VI, the possibility that FF/VI can be administered once-daily, and the attractive characteristics of Ellipta are important features that could help FF/VI to be a successful combination in the treatment of chronic obstructive pulmonary disease.

  18. Effect of sprint training on resting serum irisin concentration - Sprint training once daily vs. twice every other day.

    Tsuchiya, Yoshifumi; Ijichi, Toshiaki; Goto, Kazushige

    2016-04-01

    Exercise twice every other day has been shown to lead to increasing peroxisome proliferator receptor γ coactivator-1α (PGC-1α) expression (up-stream factor of irisin) via lowered muscle glycogen level during second of exercise compared with exercise once daily. This study determined the influence of 4weeks of sprint training (training once daily vs. twice every other day) on the serum irisin concentration. Twenty healthy males (20.9±1.3years) were assigned randomly to either the SINGLE or REPEATED group (n=10 per group). The subjects in the SINGLE group participated in a sprint training session once daily (5days per week), whereas those in the REPEATED group performed two consecutive training sessions on the same day with a 1-h rest between sessions (2-3days per week). Both groups completed 20 training sessions over 4weeks. Each training session consisted of three consecutive 30-s maximal pedaling exercises with a 10-min rest between sets. Blood samples were collected before and after training period (48h after completing the last training session). The serum irisin concentration decreased significantly after training in each group (SINGLE, 338.5±77.8 to 207.6±64.6ng/mL; REPEATED, 329.5±83.9 to 234.2±72.8ng/mL, pevery other day). Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Once-daily dose regimen of ribavirin is interchangeable with a twice-daily dose regimen: randomized open clinical trial

    Balk JM

    2015-08-01

    Full Text Available Jiska M Balk,1 Guido RMM Haenen,1 Özgür M Koc,2 Ron Peters,3 Aalt Bast,1 Wim JF van der Vijgh,1 Ger H Koek,4 1Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, 2Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, 3DSM Resolve, Geleen, 4Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands Background: The combination of ribavirin (RBV and pegylated interferon (PEG-IFN is effective in the treatment of chronic hepatitis C infection. Reducing the frequency of RBV intake from twice to once a day will improve compliance and opens up the opportunity to combine RBV with new and more specific direct-acting agents in one pill. Therefore, the purpose of this study was to evaluate the pharmacokinetic profile of RBV in a once-daily to twice-daily regimen. The secondary aim was to determine tolerability as well as the severity and differences in side effects of both treatment regimens. Methods: In this randomized open-label crossover study, twelve patients with chronic type 1 hepatitis C infection and weighing more than 75 kg were treated with 180 µg of PEG-IFN weekly and 1,200 mg RBV daily for 24 weeks. The patients received RBV dosed as 1,200 mg once-daily for 12 weeks followed by RBV dosed as 600 mg twice-daily for 12 weeks, or vice versa. In addition to the pharmacokinetic profile, the hematological profile and side effects were recorded. The RBV concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Results: Eight of twelve patients completed the study. Neither the time taken for RBV to reach peak plasma concentration nor the AUC0-last (adjusted for difference in dose was significantly different between the two groups (P>0.05. Furthermore, the once-daily regimen did not give more side effects than the twice-daily regimen (P>0

  20. Clinical efficacy of levofloxacin 500 mg once daily for 7 days for patients with non-gonococcal urethritis.

    Takahashi, Satoshi; Ichihara, Kohji; Hashimoto, Jiro; Kurimura, Yuichiro; Iwasawa, Akihiko; Hayashi, Kenji; Sunaoshi, Kenichi; Takeda, Koichi; Suzuki, Nobukazu; Satoh, Takashi; Tsukamoto, Taiji

    2011-06-01

    To confirm the efficacy of the treatment regimen with oral levofloxacin (LVFX) 500 mg once daily for 7 days for patients with non-gonococcal urethritis (NGU), we evaluated the microbiological and clinical outcomes of the regimen in those patients. We finally evaluated 53 patients with symptomatic NGU and 5 patients with asymptomatic NGU. As a result of microbiological examinations, 19 of the symptomatic patients were diagnosed as having non-gonococcal chlamydial urethritis (NGCU); 13 had non-gonococcal non-chlamydial urethritis (NGNCU), and 21 had urethritis without any microbial detection. Five of the asymptomatic patients were diagnosed as having NGCU. Microbiological cure was achieved in 91% of the 32 patients with symptomatic NGU and in 80% of the 5 patients with asymptomatic NGCU. Clinical cure was obtained in 92% of the 53 patients with symptomatic NGU. The microbiological eradication rate for Chlamydia trachomatis was 92% in 24 patients. As for other organisms, the microbiological eradication rate for Mycoplasma genitalium was 60% in 5 patients and that for Ureaplasma urealyticum was 100% in 10. The microbiological and clinical efficacy of oral LVFX 500 mg once daily for 7 days for the patients with NGU was the same for the azithromycin (AZM) 1,000 mg single dose that we previously reported. The eradication rates of C. trachomatis and U. urealyticum in the treatment regimen with LVFX 500 mg were high enough in the clinical setting; however, for M. genitalium, the rate was relatively inferior to that with AZM.

  1. Clinical impact of laboratory error on therapeutic drug monitoring of once-daily tobramycin in cystic fibrosis: Case series

    William A Prescott

    2014-01-01

    Full Text Available Once-daily dosing intravenous tobramycin is commonly used to treat cystic fibrosis pulmonary exacerbations. Clinicians often utilize historical therapeutic drug monitoring data to individualize the dose among patients who have been treated with tobramycin previously. This case series involves three patients with cystic fibrosis who had supra-therapeutic tobramycin levels despite use of a once-daily dosing that produced therapeutic drug levels during a previous hospital admission, raising questions about the validity of these levels. Investigation into several potential sources of error led to the discovery of an analyzer error in the laboratory. Once the laboratory’s tobramycin analyzer was recalibrated, the reported levels were comparable to historical levels. This case series emphasizes the clinical importance of critically analyzing reported levels, and specifically, the importance of utilizing past therapeutic drug monitoring data, if available, for all patients treated with intravenous tobramycin. If a patient was therapeutic on a similar dose of tobramycin during a previous admission, a dose adjustment may not be necessary, and clinicians should consider repeating levels while pursuing alternative explanations for the discrepant serum levels.

  2. Once-Daily Tacrolimus Extended-Release Formulation: 1 Year after Conversion in Stable Pediatric Kidney Transplant Recipients

    Lars Pape

    2011-01-01

    Full Text Available It is speculated that a once-daily dosage of immunosuppression can increase adherence and thereby graft survival. Until now, there have been no studies on once-daily use of Tacrolimus extended-release formulation (TAC-ER in children following pediatric kidney transplantation. In 11 stable pediatric kidney recipients >10 years, efficacy, safety, and tolerability of a switch to TAC-ER were observed over one year. Adherence was determined by use of the BAASIS-Scale Interview and comparison of individual variability of Tacrolimus trough levels. Over the observation period, two acute rejections were observed in one girl with nonadherence and repeated Tacrolimus trough levels of 0 ng/m. Beside this, there were no acute rejections in this trial. TAC dose was increased in 3/11 patients and decreased in 2/11 patients within the course of the study. Six patients did not require a dose adjustment. All but one patient had a maximum of 1 dose change during therapy. Mean Tacrolimus dose, trough levels, and Glomerular filtration rates were also stable. Adherence, as measured by BAASIS-Scale Interview and coefficient of variation of Tacrolimus trough levels, was good at all times. It is concluded that conversion to Tac-ER is safe in low-risk children following pediatric kidney transplantation.

  3. Evaluation of Flexible Tacrolimus Drug Concentration Monitoring Approach in Patients Receiving Extended-Release Once-Daily Tacrolimus Tablets.

    Philosophe, Benjamin; Leca, Nicolae; West-Thielke, Patricia M; Horwedel, Timothy; Culkin-Gemmell, Christine; Kistler, Kristin; Stevens, Daniel R

    2018-02-20

    The majority of United States kidney transplant patients are treated with tacrolimus, a drug effective in preventing graft rejection, but with a narrow therapeutic range, necessitating close monitoring to avoid increased risks of transplant rejection or toxicity if the tacrolimus concentration is too low or too high, respectively. The trough drug concentration tests are time sensitive; patients treated on a twice-daily basis have blood draws exactly 12 hours after their previous dose. The schedule's rigidity causes problems for both patients and health care providers. Novel once-daily tacrolimus formulations such as LCPT (an extended-release tablet by Veloxis Pharmaceuticals, Inc., Cary, North Carolina) have allowed for blood draws on a once-daily basis; however, even that schedule can be restrictive. Results from tests taken either before or after that 24-hour target time may be discarded, or worse, may lead to inappropriate dose changes. Data from ASTCOFF, a phase 3B pharmacokinetic clinical trial (NCT02339246), demonstrated that the unique pharmacokinetic curve of LCPT may allow for a therapeutic monitoring window that extends for 3 hours before or after the 24-hour monitoring target. Furthermore, important tools to help clinicians interpret these levels, such as formulas to estimate the 24-hour trough level if an alternative monitoring time is used, were constructed from these data. These study results give treating clinicians access to data that allow them to safely use and monitor LCPT in their patients and expand the body of evidence surrounding differentiation and practical application of the novel LCPT tacrolimus formulation. © 2018, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  4. Pharmacokinetics of a once-daily extended-release formulation of pramipexole in healthy male volunteers: three studies.

    Jenner, Peter; Könen-Bergmann, Michael; Schepers, Cornelia; Haertter, Sebastian

    2009-11-01

    Pramipexole is a dopamine agonist used in the treatment of Parkinson's disease. The currently available immediate-release (IR) formulation is taken orally 3 times daily. These studies were conducted to evaluate the pharmacokinetic properties of a variety of prototypes for a once-daily extended-release (ER) formulation of pramipexole and to further characterize the prototype whose pharmacokinetics best matched those of the IR formulation. Three Phase I studies were conducted, all in healthy adult men aged food effect. In the third study, steady-state pharmacokinetics of the optimal ER formulation were assessed across a range of pramipexole doses (0.375-4.5 mg/d), including investigation of the food effect at steady state for the highest dose. Tolerability was assessed throughout all studies based on physical examinations, laboratory measurements, and adverse events (AEs). The 3 studies included 18, 15, and 39 subjects, respectively. Among the ER prototypes tested at 0.75 mg once daily in study 1, a matrix tablet had the optimal pharmacokinetic resemblance to IR pramipexole 0.25 mg TID, with a geometric mean AUC(0-24h,ss) of 17.4 ng.h/mL (vs 16.0 ng.h/mL for the IR formulation), C(max,ss) of 0.967 ng/mL (vs 1.09 ng/mL), and C(min,ss) of 0.455 ng/mL (vs 0.383 ng/mL). For single-dose ER 0.375 mg administered in the fasted state in study 2, in vivo bioavailability was predictable from in vitro dissolution data, with internal mean absolute percent prediction errors of 3.18% for AUC(0-30h) and 4.87% for C(max), and external mean absolute prediction errors of 6.61% and 3.34%, respectively, satisfying current guidelines for a level A IVIVC. For single-dose ER 0.375 mg administered in the fed state, the upper bound of the 90% CI for fed:fasted values was 119.8 for AUC(0-30h) (within the bioequivalence limits of 80%-125%) and 134.1 for C(max). At steady state in study 3 (subjects' 5th treatment day), dosing at 0.375 to 4.5 mg in the fasted state was associated with a linear

  5. Accelerated partial breast irradiation using once-daily fractionation: analysis of 312 cases with four years median follow-up

    Shaikh Arif Y

    2012-02-01

    Full Text Available Abstract Background There are limited data on accelerated partial breast irradiation (APBI using external beam techniques. Moreover, there are recent reports of increased fibrosis and unacceptable cosmesis with APBI using external beam with BID fractionation. We adopted a once daily regimen of APBI with fractionation similar to that shown to be effective in a Canadian randomized trial of whole breast irradiation. It is unclear whether patients with DCIS or invasive lobular carcinoma (ILC are suitable for APBI. Methods The retrospective cohort included 310 patients with 312 tumors of T1-T2N0-N1micM0 invasive ductal carcinoma (IDC, ILC, or Tis (DCIS treated with APBI via external beam. Most patients were treated using IMRT with 16 daily fractions of 270 cGy to a dose of 4320 cGy. The target volume included the lumpectomy cavity plus 1.0 cm to account for microscopic disease and an additional 0.5 to 1.0 cm for setup uncertainty and breathing motion. Ipsilateral breast failure (IBF was pathologically confirmed as a local failure (LF or an elsewhere failure (EF. Results Median follow-up was 49 months. Among the 312 cases, 213 were IDC, 31 ILC, and 68 DCIS. Median tumor size was 1.0 cm. There were 9 IBFs (2.9% including 5 LFs and 4 EFs. The IBF rates among patients with IDC, ILC, and DCIS were 2.4%, 3.2%, and 4.4%, respectively, with no significant difference between histologies. When patients were analyzed by the ASTRO APBI consensus statement risk groups, 32% of treated cases were considered suitable, 50% cautionary, and 18% unsuitable. The IBF rates among suitable, cautionary, and unsuitable patients were 4.0%, 2.6%, and 1.8%, respectively, with no significant difference between risk groups. Acute skin reactions were rare and long-term cosmetic outcome was very good to excellent. Conclusions External beam APBI with once daily fractionation has a low rate of IBF consistent with other published APBI studies. The ASTRO risk stratification did not

  6. Pharmacokinetic Comparison of Once-Daily Topical Minocycline Foam 4% vs Oral Minocycline for Moderate-to-Severe Acne.

    Jones, Terry M; Ellman, Herman; deVries, Tina

    2017-10-01

    To characterize minocycline pharmacokinetics and relative bioavailability following multiple-dose topical administration of minocycline hydrochloride (HCl) foam 4% (FMX101 4%) as compared with single-dose oral administration of minocycline HCl extended-release tablets (Solodyn®) in subjects with moderate-to-severe acne. A Phase 1, single-center, nonrandomized, open-label, active-controlled, 2-period, 2-treatment crossover clinical study. The study included 30 healthy adults (mean age, 22.6 years; 90% white, and 60% females) who had moderate-to-severe acne. Subjects were assigned to first receive a single oral dose of a minocycline HCl extended-release tablet (approximately 1 mg/kg). At 10 days after the oral minocycline dose, topical minocycline foam 4% was applied, once daily for 21 days. Serial blood samples were obtained before and after administration of oral minocycline and each topical application of minocycline foam 4% on days 1, 12, and 21. Following oral administration of minocycline (approximately 1 mg/kg), plasma minocycline concentration increased until 3 hours, followed by a log-linear decrease over the remainder of the 96-hour sampling period. Following topical application of a 4-g maximal-use dose of minocycline foam 4% for 21 days, plasma minocycline concentration was very low, with geometric mean Cmax values ranging from 1.1 ng/mL to 1.5 ng/mL. Steady state was achieved by day 6. Overall, minocycline exposure with topical minocycline foam 4% was 730 to 765 times lower than that with oral minocycline. There was no evidence of minocycline accumulation over the 21 days of topical application of minocycline foam 4%. Topical minocycline foam 4% appeared to be safe and well tolerated, with no serious treatment-emergent adverse events (TEAEs), treatment-related TEAEs, or TEAEs that led to treatment discontinuation. Once-daily topical application of minocycline foam 4% did not lead to significant systemic exposure to minocycline. It appears to be a well

  7. Nasal deposition of ciclesonide nasal aerosol and mometasone aqueous nasal spray in allergic rhinitis patients.

    Emanuel, Ivor A; Blaiss, Michael S; Meltzer, Eli O; Evans, Philip; Connor, Alyson

    2014-01-01

    Sensory attributes of intranasal corticosteroids, such as rundown to the back of the throat, may influence patient treatment preferences. This study compares the nasal deposition and nasal retention of a radiolabeled solution of ciclesonide nasal aerosol (CIC-hydrofluoroalkane [HFA]) with a radiolabeled suspension of mometasone furoate monohydrate aqueous nasal spray (MFNS) in subjects with either perennial allergic rhinitis (AR) or seasonal AR. In this open-label, single-dose, randomized, crossover scintigraphy study, 14 subjects with symptomatic AR received a single dose of radiolabeled 74-μg CIC-HFA (37 μg/spray, 1 spray/each nostril) via a nasal metered-dose inhaler or a single dose of radiolabeled 200-μg MFNS (50 μg/spray, 2 sprays/each nostril), with a minimum 5-day washout period between treatments. Initial deposition (2 minutes postdose) of radiolabeled CIC-HFA and MFNS in the nasal cavity, nasopharynx, and on nasal wipes, and retention of radioactivity in the nasal cavity and nasal run-out on nasal wipes at 2, 4, 6, 8, and 10 minutes postdose were quantified with scintigraphy. At 2 and 10 minutes postdose, deposition of radiolabeled CIC-HFA was significantly higher in the nasal cavity versus radiolabeled MFNS (99.42% versus 86.50% at 2 minutes, p = 0.0046; and 81.10% versus 54.31% at 10 minutes, p Deposition of radioactivity on nasal wipes was significantly higher with MFNS versus CIC-HFA at all five time points, and posterior losses of radiolabeled formulation were significantly higher with MFNS at 6, 8, and 10 minutes postdose. In this scintigraphic study, significantly higher nasal deposition and retention of radiolabeled aerosol CIC-HFA were observed versus radiolabeled aqueous MFNS in subjects with AR.

  8. Once-daily omeprazole/sodium bicarbonate heals severe refractory reflux esophagitis with morning or nighttime dosing.

    Orbelo, Diana M; Enders, Felicity T; Romero, Yvonne; Francis, Dawn L; Achem, Sami R; Dabade, Tushar S; Crowell, Michael D; Geno, Debra M; DeJesus, Ramona S; Namasivayam, Vikneswaran; Adamson, Steven C; Arora, Amindra S; Majka, Andrew J; Alexander, Jeffrey A; Murray, Joseph A; Lohse, Matthew; Diehl, Nancy N; Fredericksen, Mary; Jung, Kee Wook; Houston, Margaret S; O'Neil, Angela E; Katzka, David A

    2015-01-01

    Morning dose or twice-daily proton pump inhibitor (PPI) use is often prescribed to heal severe reflux esophagitis. Compare the effect of single dose morning (control arm) versus nighttime (experimental arm) omeprazole/sodium bicarbonate (Zegerid(®)) (IR-OME) on esophagitis and gastroesophageal reflux symptoms. Adult outpatients with Los Angeles grade C or D esophagitis were allocated to open-label 40 mg IR-OME once a day for 8 weeks in a prospective, randomized, parallel design, single center study. Esophagogastroduodenoscopy (EGD) and validated self-report symptom questionnaires were completed at baseline and follow-up. Intention-to-treat and per-protocol analyses were performed. Ninety-two of 128 (72 %) eligible subjects participated [64 (70 %) male, mean age 58 (range 19-86), median BMI 29 (range 21-51), 58 C:34 D]. Overall, 81 (88 %) subjects healed [n = 70 (76 %)] or improved [n = 11 (12 %)] erosions. There was no significant difference (morning vs. night) in mucosal healing [81 vs. 71 %, (p = 0.44)] or symptom resolution [heartburn (77 vs. 65 %, p = 0.12), acid regurgitation (82 vs. 73 %, p = 0.28)]. Prevalence of newly identified Barrett's esophagus was 14 % with half diagnosed only after treatment. Once-daily IR-OME (taken morning or night) effectively heals severe reflux esophagitis and improves GERD symptoms. Results support the clinical practice recommendation to repeat EGD after 8 weeks PPI therapy in severe esophagitis patients to assure healing and exclude Barrett's esophagus.

  9. Comparison of health care resource utilization and costs among patients with GERD on once-daily or twice-daily proton pump inhibitor therapy

    Mody R

    2013-04-01

    Full Text Available Reema Mody,1 Debra Eisenberg,2 Likun Hou,2 Siddhesh Kamat,2 Joseph Singer,2 Lauren B Gerson3 1Takeda Pharmaceuticals International Inc, Deerfield, IL, 2HealthCore Inc, Wilmington, DE, 3Stanford University School of Medicine, Stanford, CA, USA Background: The purpose of this study was to assess differences in health care resource utilization and costs associated with once-daily and twice-daily proton pump inhibitor (PPI therapy. Most patients with gastroesophageal reflux disease (GERD achieve symptom control on once-daily PPI therapy, but approximately 20%–30% require twice-daily dosing. Methods: Patients were ≥18 years of age with at least one medical claim for GERD and at least two PPI claims from HealthCore's Integrated Research Database (HIRDSM during 2004–2009. Patients were continuously eligible for 12 months before and after the index date (date of first PPI claim. Based on PPI dosing throughout the post-index period (quantity of medication dispensed/number of days supply, patients were classified as once-daily (dose ≤ 1.5 pills per day or twice-daily (≥1.5 PPI users. Results: The study cohort included 248,386 patients with GERD (mean age 52.8 ± 13.93 years, 56% females of whom 90% were once-daily and 10% were twice-daily PPI users. The Deyo-Charlson Comorbidity Index for once-daily and twice-daily PPI users was 0.70 ± 1.37 and 0.89 ± 1.54, respectively (P < 0.05. More once-daily patients had claims for Barrett's esophagus (5% versus 2%, P < 0.0001 than twice-daily patients. Post-index, higher proportions of twice-daily patients had at least one GERD-related inpatient visit (7% versus 5%, outpatient visit (60% versus 49%, and office visit (48% versus 38% versus once-daily patients (P < 0.0001. Mean total GERD-related health care costs were $2065 ± $6636 versus $3749 ± $11,081 for once-daily and twice-daily PPI users, respectively (P < 0.0001. Conclusion: Patients receiving twice-daily PPI therapy were likely to have more

  10. Safety and Efficacy of Once-Daily Intravenous Busulfan in Allogeneic Transplantation: A Matched-Pair Analysis.

    Kako, Shinichi; Fujiwara, Shinichiro; Sato, Miki; Kimura, Shun-Ichi; Nakasone, Hideki; Ohashi, Kazuteru; Kawakita, Toshiro; Maeda, Tetsuo; Morishita, Takanobu; Suzuki, Ritsuro; Fukuda, Takahiro; Ichinohe, Tatsuo; Kurata, Mio; Atsuta, Yoshiko; Kanda, Yoshinobu

    2018-04-19

    Compared with 4-times-daily infusion of intravenous busulfan (ivBU4), the safety and efficacy of once-daily infusion of ivBU (ivBU1) has not been fully clarified. We have been routinely using ivBU1 in a conditioning regimen in adult patients with myeloid malignancy who undergo allogeneic hematopoietic stem cell transplantation. In this study, a total of 91 patients who received ivBU1 for 2 days (n = 18) or 4 days (n = 73) in our institutions were compared with 273 control patients who received ivBU4, who were matched for age, sex, performance status, disease risk, conditioning regimen, and donor type, selected from the database of the Japanese Society for Hematopoietic Cell Transplantation using optimal matching algorithms. One-year overall survival (56.8% versus 57.1%, P = .94), disease-free survival (51.6% versus 50.8%, P = .73), relapse rate (28.5% versus 26.2%, P = .94), nonrelapse mortality (19.9% versus 23.0%, P = .71), and the incidence of graft-versus-host disease were not significantly different between the ivBU1 and ivBU4 groups. In patients who received ivBU1, neutrophil recovery was slower (median days: 22 versus 17, P = .001), and the incidence of veno-occlusive disease was lower (2.6% versus 17.4%, P = .04). In conclusion, ivBU1 can be safely administered with clinical outcomes similar to those with ivBU4. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  11. Comparison of once-daily versus twice-daily dosing of valsartan in patients with chronic stable heart failure

    Inder S Anand

    2010-06-01

    Full Text Available Inder S Anand1, Anita Deswal2, Dean J Kereiakes3, Das Purkayastha4, Dion H Zappe41Veterans Administration Medical Center, Minneapolis, MN, USA; 2Michael E DeBakey VA Medical Center, Houston, TX, USA; 3The Christ Hospital Heart and Vascular Center, Cincinnati, OH, USA; 4Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; Clinical trial registration information: www.clinicaltrials.gov/ct2/show/NC T00294086 Unique identification number: NC T00294086Background: The safety of once-daily (qd dosing of valsartan in heart failure (HF patients is not known. Hypothesis: This 10-week, double-blind trial examined the relative safety and efficacy of valsartan administered qd versus twice-daily (bid.Methods: HF patients (NYHA class II–III receiving diuretics (87%, angiotensin-converting enzyme inhibitors (98%, beta-blockers (92%, aldosterone antagonists (25%, or digoxin (32% were randomized to valsartan 40 mg bid (n = 60 or 80 mg qd (n = 55 and titrated to a maximum dose of 320 mg/day; doubling the dose every 2 weeks. Clinical and biochemical parameters were measured at Weeks 2, 4, 6, and 10.Results: The average dose of valsartan at the end of study was 245 mg in the bid group vs 256 mg in the qd group (P = NS. Similar proportions of patients tolerated qd vs bid dosing (bid 67% vs qd 68%. Outcome measures including reduction in blood pressure, incidence of hypotension, renal impairment, orthostatic dizziness or fatigue, changes in serum K+, creatinine, cystatin-C, and estimated glomerular filtration rate were similar between the 2 groups at all time-points. Brain natriuretic peptide levels decreased and plasma renin activity increased from baseline by the same amount in both groups at all time-points.Conclusion: Valsartan administered qd has a similar safety and tolerability profile with comparable 24-hour RAAS blockade, as assessed by increases in PRA, as bid dosing in patients with moderate to severe (NYHA class II–III heart failure

  12. Effect of once-daily insulin detemir on oral antidiabetic drug (OAD) use in patients with type 2 diabetes.

    Vora, J; Caputo, S; Damci, T; Orozco-Beltran, D; Pan, C; Svendsen, A L; Sølje, K S; Khunti, K

    2014-04-01

    There are acknowledged benefits to continuing metformin when initiating insulin, but there appears to be growing concern over the role of sulphonylureas and thiazolidinediones when used in combination with insulin. This analysis investigates the effects of continuing or discontinuing oral antidiabetic drugs (OADs) following the initiation of once-daily insulin detemir. SOLVE is a 24-week, multinational observational study of insulin detemir initiation in patients with type 2 diabetes mellitus treated with one or more OADs. In the total cohort (n = 17 374), there were significant improvements in HbA1c (-1·3%, 95% CI -1·34; -1·27%) and weight (-0·6 kg, 95% CI -0·65; -0·47 kg), with an increase in the incidence rate of minor hypoglycaemia (+0·256 events ppy, P use either prior to (n = 17 086) or during insulin initiation (n = 16 346). HbA1c reductions were significantly greater in patients continuing treatment with metformin (-1·3% vs. -1·1%, P < 0·01), thiazolidinediones (-1·3% vs. -1·0%, P < 0·01) and DPP-IV inhibitors (-1·3% vs. -0·9%, P < 0·001). Final insulin doses were significantly greater in patients discontinuing treatment with sulphonylureas (0·29 vs. 0·26 IU/kg, P < 0·001), glinides (0·28 vs. 0·26 IU/kg, P < 0·01), thiazolidinediones (0·31 vs. 0·26 IU/kg, P < 0·001) and DPP-IV inhibitors (0·35 vs. 0·29 IU/kg, P < 0·001) compared with patients continuing these respective agents. All patient subgroups had a mean weight loss irrespective of OAD continuation, apart from those continuing thiazolidinediones (+0·2 kg). The largest improvements in weight were seen following the withdrawal of sulphonylureas and thiazolidinediones (-1·1 and -1·1 kg, respectively). Discontinuation (or switching) of OADs at the time of insulin initiation appears to be governed principally by concerns about hypoglycaemia and weight. HbA1c improvements were smaller in patients discontinuing OADs at the time of insulin

  13. Tamsulosin 0.4 mg once daily: effect on sexual function in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction

    Höfner, K.; Claes, H.; de Reijke, T. M.; Folkestad, B.; Speakman, M. J.

    1999-01-01

    To evaluate the effect of tamsulosin, 0.4 mg once daily, on sexual function in comparison with placebo and alfuzosin, 2.5 mg three times daily, in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO). Data from 830 patients randomized into three European

  14. Pharmacodynamics and Pharmacokinetics Following Once-Daily and Twice-Daily Dosing of Tiotropium Respimat(®) in Asthma Using Standardized Sample-Contamination Avoidance

    Beeh, Kai-Michael; Kirsten, Anne-Marie; Dusser, Daniel

    2016-01-01

    BACKGROUND: This study was conducted to confirm the 24-hour bronchodilator efficacy and pharmacokinetic profile of once-daily tiotropium Respimat(®) 5 μg add-on to inhaled corticosteroids (ICS) in adults with symptomatic asthma. It used a trial protocol designed to minimize the risk of pharmacoki...

  15. Twice-daily versus once-daily applications of pimecrolimus cream 1% for the prevention of disease relapse in pediatric patients with atopic dermatitis.

    Ruer-Mulard, Mireille; Aberer, Werner; Gunstone, Anthony; Kekki, Outi-Maria; López Estebaranz, Jose Luis; Vertruyen, André; Guettner, Achim; Hultsch, Thomas

    2009-01-01

    The aim of this study is to compare twice-daily and once-daily applications of pimecrolimus cream 1% for prevention of atopic dermatitis relapses in pediatric patients. This multicenter trial enrolled 300 outpatients aged 2 to 17 years, with mild-to-severe atopic dermatitis. The patients were initially treated with twice-daily topical pimecrolimus until complete clearance or for up to 6 weeks (open-label period). Those who achieved a decrease of at least 1 point in the Investigator's Global Assessment score were then randomized to double-blind treatment with pimecrolimus cream 1% either twice daily or once daily for up to 16 weeks. Study medication was discontinued during periods of disease remission (Investigator's Global Assessment = 0). The primary efficacy end point of the double-blind phase was disease relapse (worsening requiring topical corticosteroids or additional/alternative therapy and confirmed by Investigator's Global Assessment score > or = 3 and pruritus score > or = 2). Of the 300 patients enrolled in the study, 268 were randomized to treatment with pimecrolimus cream 1% either twice daily or once daily (n = 134 in each group). The relapse rate was lower in the twice-daily dose group (9.9%) than that in the once-daily dose group (14.7%), but analysis of the time to disease relapse, using a Cox proportional model to adjust for confounding variables, did not show a statistically significant difference between treatment arms (hazard ratio: 0.64; 95% CI: 0.31-1.30). Treatment of active atopic dermatitis lesions with pimecrolimus cream 1% twice daily, followed by the once-daily dosing regimen, was sufficient to prevent subsequent atopic dermatitis relapses over 16 weeks in pediatric patients.

  16. Open-Label Single-Sequence Crossover Study Evaluating Pharmacokinetics, Efficacy, and Safety of Once-Daily Dosing of Nitisinone in Patients with Hereditary Tyrosinemia Type 1.

    Guffon, Nathalie; Bröijersén, Anders; Palmgren, Ingrid; Rudebeck, Mattias; Olsson, Birgitta

    2018-01-01

    Although nitisinone is successfully used to treat hereditary tyrosinemia type 1 (HT-1) with the recommended twice-daily dosing, data describing a long half-life motivate less frequent dosing. Therefore, in agreement with the Pharmacovigilance Risk Assessment Committee at the European Medicines Agency, this study was performed to investigate the switch to once-daily dosing. This open-label, non-randomized, single-sequence crossover study evaluated the pharmacokinetics, efficacy, and safety of once-daily compared to twice-daily dosing of nitisinone in patients with HT-1 (NCT02323529). Well-controlled patients of dry blood spots by tandem mass spectrometry. The primary endpoint was C min of nitisinone after ≥4 weeks of treatment on each dosing regimen. Secondary objectives were evaluation of efficacy and safety during each dosing regimen. In total, 19 patients were enrolled and 17 included in the per-protocol analysis set. The mean (SD) nitisinone C min decreased by 23%, from 26.4 (10.2) to 21.2 (9.9) μmol/L in dry blood spot samples (not equivalent to plasma concentrations), when patients switched from twice- to once-daily dosing. There was no apparent age- or bodyweight-related trend in the degree of C min decrease. No patient had quantifiable succinylacetone levels during the once-daily treatment period, indicating efficacious treatment. All adverse events were mild or moderate and judged unrelated to nitisinone. The switch to once-daily treatment with nitisinone appeared efficacious and safe in the treatment of patients with HT-1.

  17. Efficacy and safety of fluticasone furoate/vilanterol or tiotropium in subjects with COPD at cardiovascular risk

    Covelli H

    2015-12-01

    Full Text Available Henry Covelli,1 Bonavuth Pek,2 Isabelle Schenkenberger,3 Catherine Scott-Wilson,4 Amanda Emmett,5 Courtney Crim4 1Kootenai Health, Coeur d’Alene, ID, USA; 2Clinique de Pneumologie et de Sommeil de Lanaudière, Quebec, Canada; 3Klinische Forschung, Berlin, Germany; 4GlaxoSmithKline Inc., Research Triangle Park, 5PAREXEL International, Durham, NC, USA Background: Fluticasone furoate/vilanterol (FF/VI is a novel, once-daily, inhaled corticosteroid/long-acting β2-agonist combination approved for the treatment of COPD and asthma. We compared the safety and efficacy of FF/VI and tiotropium (TIO in subjects with moderate-to-severe COPD with greater risk for comorbid cardiovascular disease (CVD.Methods: This randomized, blinded, double-dummy, parallel-group study compared a once-daily morning dose of FF/VI 100/25 mcg delivered via ELLIPTA™ with TIO 18 mcg via HandiHaler® for 12 weeks in subjects with diagnosed COPD, forced expiratory volume in 1 second (FEV1 30%–70% predicted, and CVD or CVD risk. The primary endpoint was change from baseline in 24-hour weighted mean FEV1 on Day 84. Other efficacy endpoints included time to onset of bronchodilation, trough FEV1, other spirometry measures, rescue medication use, symptoms, quality of life (St George’s Respiratory Questionnaire-COPD [SGRQ-C], and health status (COPD Assessment Tests [CAT] measures. Safety endpoints included cardiovascular monitoring, cortisol excretion, COPD exacerbations, and adverse events, including prespecified drug effects.Results: Both FF/VI and TIO improved the 24-hour weighted mean FEV1 from baseline after 12 weeks with no significant difference between treatments. Other endpoints favored FF/VI for time to onset of bronchodilation, rescue medication use, dyspnea, SGRQ-C and CAT scores, or favored TIO for change from baseline in forced vital capacity and inspiratory capacity. Pneumonia occurred more frequently in the FF/VI group, and two TIO-treated subjects died

  18. Three-year outcomes of a once daily fractionation scheme for accelerated partial breast irradiation (APBI) using 3-D conformal radiotherapy (3D-CRT)

    Goyal, Sharad; Daroui, Parima; Khan, Atif J; Kearney, Thomas; Kirstein, Laurie; Haffty, Bruce G

    2013-01-01

    The aim of this study was to report 3-year outcomes of toxicity, cosmesis, and local control using a once daily fractionation scheme (49.95 Gy in 3.33 Gy once daily fractions) for accelerated partial breast irradiation (APBI) using three-dimensional conformal radiotherapy (3D-CRT). Between July 2008 and August 2010, women aged ≥40 years with ductal carcinoma in situ or node-negative invasive breast cancer ≤3 cm in diameter, treated with breast-conserving surgery achieving negative margins, were accrued to a prospective study. Women were treated with APBI using 3–5 photon beams, delivering 49.95 Gy over 15 once daily fractions over 3 weeks. Patients were assessed for toxicities, cosmesis, and local control rates before APBI and at specified time points. Thirty-four patients (mean age 60 years) with Tis 0 (n = 9) and T1N0 (n = 25) breast cancer were treated and followed up for an average of 39 months. Only 3% (1/34) patients experienced a grade 3 subcutaneous fibrosis and breast edema and 97% of the patients had good/excellent cosmetic outcome at 3 years. The 3-year rate of ipsilateral breast tumor recurrence (IBTR) was 0% while the rate of contralateral breast events was 6%. The 3-year disease-free survival (DFS), overall survival (OS), and breast cancer-specific survival (BCSS) was 94%, 100%, and 100%, respectively. Our novel accelerated partial breast fractionation scheme of 15 once daily fractions of 3.33 Gy (49.95 Gy total) is a remarkably well-tolerated regimen of 3D-CRT-based APBI. A larger cohort of patients is needed to further ascertain the toxicity of this accelerated partial breast regimen

  19. Conversion From Twice-Daily Tacrolimus Capsules to Once-Daily Extended-Release Tacrolimus (LCPT): A Phase 2 Trial of Stable Renal Transplant Recipients

    Gaber, A. Osama; Alloway, Rita R.; Bodziak, Kenneth; Kaplan, Bruce; Bunnapradist, Suphamai

    2013-01-01

    Background LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Phase 1 studies demonstrated greater bioavailability to twice-daily tacrolimus capsules and no new safety concerns. Methods In this phase 2 study, adult stable kidney transplant patients on tacrolimus capsules (Prograf) twice-daily were converted to tacrolimus tablets (LCP-Tacro) once-daily; patients continued on LCP-Tacro once-daily for days 8 to 21; trough levels were to be maintained between 5 and 15 ng/mL; 24-hr pharmacokinetic assessments were done on days 7 (baseline pre-switch), 14, and 21. Results Forty-seven patients completed LCP-Tacro dosing per protocol. The mean conversion ratio was 0.71. Pharmacokinetic data demonstrated consistent exposure (AUC) at the lower conversion dose. Cmax (P=0.0001), Cmax/Cmin ratio (P<0.001), percent fluctuation (P<0.0001), and swing (P=0.0004) were significantly lower and Tmax significantly (P<0.001) longer for LCP-Tacro versus Prograf. AUC24 and Cmin correlation coefficients after 7 and 14 days of therapy were 0.86 or more, demonstrating a robust correlation between LCP-Tacro tacrolimus exposure and trough levels. There were three serious adverse events; none were related to study drug and all were resolved. Conclusions Stable kidney transplant patients can be safely converted from Prograf twice-daily to LCP-Tacro. The greater bioavailability of LCP-Tacro allows for once-daily dosing and similar (AUC) exposure at a dose approximately 30% less than the total daily dose of Prograf. LCP-Tacro displays flatter kinetics characterized by significantly lower peak-trough fluctuations. PMID:23715050

  20. Maintenance of heartburn relief after step-down from twice-daily proton pump inhibitor to once-daily dexlansoprazole modified release.

    Fass, Ronnie; Inadomi, John; Han, Cong; Mody, Reema; O'Neil, Janet; Perez, M Claudia

    2012-03-01

    Many patients with gastroesophageal reflux disease (GERD) take a proton pump inhibitor (PPI) twice daily to control symptoms. Once-daily dexlansoprazole modified release (MR) has a dual-delayed release formulation, making it attractive for step-down management of patients whose symptoms are well controlled on twice-daily PPIs. We investigated whether step-down to once-daily dexlansoprazole controls heartburn in patients with GERD who were receiving twice-daily PPI therapy. Patients 18 years and older taking a twice-daily PPI for symptom control were enrolled (n = 178) in a single-blind, multicenter study; 163 patients completed the study and 142 patients met criteria for the efficacy analysis. During the 6-week screening and treatment periods, patients recorded the presence of heartburn symptoms twice daily in electronic diaries. Patients' heartburn was considered well controlled if they had an average of 1 symptom or fewer per week during the last 4 weeks of screening and treatment. After screening, qualified patients were switched to masked dexlansoprazole MR 30 mg and placebo for 6 weeks. The primary efficacy end point was the proportion of patients whose heartburn remained well controlled after step-down. GERD-related symptoms and quality of life (QOL) also were evaluated using the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) and the PAGI-QOL questionnaires, respectively. After step-down to once-daily dexlansoprazole MR 30 mg, heartburn remained well controlled in 88% of patients (125 of 142). These patients were able to maintain their GERD-related symptom severity and QOL, indicated by marginal changes in the PAGI-SYM and PAGI-QOL total and subscale scores, respectively. Most patients with GERD who take twice-daily PPI to control heartburn are able to successfully step down to once-daily dexlansoprazole 30 mg. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  1. A randomized, single-blind trial of 5% minoxidil foam once daily versus 2% minoxidil solution twice daily in the treatment of androgenetic alopecia in women.

    Blume-Peytavi, Ulrike; Hillmann, Kathrin; Dietz, Ekkehart; Canfield, Douglas; Garcia Bartels, Natalie

    2011-12-01

    Although twice-daily application of propylene glycol-containing 2% minoxidil topical solution (MTS) stimulates new hair growth, higher concentrations of minoxidil in a once-daily, propylene glycol-free formulation may improve efficacy and reduce unpleasant side effects. We sought to compare the efficacy, safety, and acceptability and to show noninferiority of once-daily 5% minoxidil topical foam (MTF) with twice-daily 2% MTS in women with androgenetic alopecia. A total of 113 women with androgenetic alopecia were randomized to 24 weeks of treatment with 5% MTF or 2% MTS. The primary efficacy parameter was change from baseline in nonvellus target area hair count at week 24. Secondary end points included change in nonvellus target area hair width, overall efficacy by global photographic review as assessed by treatment-blinded evaluators and the subject herself, adverse events, and participants' assessment of product aesthetics. After 24 weeks, women randomized to 5% MTF once daily showed noninferior target area hair count and target area hair width and experienced greater, but nonsignificant, improvements in target area hair count, target area hair width, and overall efficacy by global photographic review than those randomized to 2% MTS used twice daily. 5% MTF was significantly superior to 2% MTS in participants' agreement with "the treatment does not interfere with styling my hair" (P = .002). Women randomized to 5% MTF experienced significantly lower rates of local intolerance (P = .046) especially in pruritus and dandruff compared with 2% MTS. Because of differences in the formulations tested, study participants were not blinded to treatment. Once-daily 5% MTF is noninferior and as effective for stimulating hair growth as twice-daily 2% MTS in women with androgenetic alopecia and is associated with several aesthetic and practical advantages. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  2. Adherence to and Acceptance of Once-Daily Tacrolimus After Kidney and Liver Transplant: Results From OSIRIS, a French Observational Study.

    Cassuto, Elisabeth; Pageaux, Georges P; Cantarovich, Diego; Rostaing, Lionel; Loupy, Alexandre; Roche, Bruno; Duvoux, Christophe; Moreau, Karine; Thervet, Eric; Mazouz, Hakim; Bourhis, Yann; Dharancy, Sébastien; Kessler, Michèle

    2016-10-01

    Adherence to immunosuppressive treatments is a major concern in transplanted patients. This 6-month French observational, longitudinal, prospective study aimed to assess patient adherence to and acceptance of once-daily tacrolimus (Advagraf) initiation in kidney and liver transplant recipients. Data from 1106 patients initiating once-daily tacrolimus during posttransplant follow-up were analyzed. Adherence and acceptance were assessed using self-administered questionnaires at inclusion and at 3 and 6 months. Mean age was 52.4 ± 13.2 years, 61.5% were men. For 94.9% of patients, once-daily tacrolimus was prescribed after switching from twice-daily tacrolimus. At inclusion, 20.9% of patients reported good treatment adherence, 72.0% minor nonadherence, and 7.1% were nonadherent. Mean general acceptance score (range, 0-100) was 77.7 (±24.7). At 3 months, adherence was improved in 21.1%, unchanged in 69.2%, and worsened in 9.7% of patients. Mean general acceptance score was 75.4 (±26.5). General acceptance score was improved in 28.0%, unchanged in 39.4%, and worsened in 32.7% of patients. At 6 months, similar changes in adherence and acceptance were observed. Higher general acceptance score at month 3 was significantly associated with better adherence at month 6. Conversion to once-daily tacrolimus led to an improved rate of adherence at month 3 in more than 20% of patients and a worsened rate of adherence in less than 10% of patients.

  3. Comparing omeprazole with fluoxetine for treatment of patients with heartburn and normal endoscopy who failed once daily proton pump inhibitors: double-blind placebo-controlled trial.

    Ostovaneh, M R; Saeidi, B; Hajifathalian, K; Farrokhi-Khajeh-Pasha, Y; Fotouhi, A; Mirbagheri, S S; Emami, H; Barzin, G; Mirbagheri, S A

    2014-05-01

    Patients with heartburn but without esophageal erosion respond less well to proton pump inhibitors (PPIs). There is a growing body of evidence implicating the role of psychological comorbidities in producing reflux symptoms. Pain modulators improve symptoms in patients with other functional gastrointestinal disorders. We aimed to compare the efficacy of fluoxetine with omeprazole and placebo to achieve symptomatic relief in patients with heartburn and normal endoscopy who failed once daily PPIs. Endoscopy-negative patients with heartburn who failed once daily PPIs were randomly allocated to receive 6 weeks treatment of fluoxetine, omeprazole, or placebo. Random allocation was stratified according to ambulatory pH monitoring study. Percentage of heartburn-free days and symptom severity was assessed. Sixty patients with abnormal and 84 patients with normal pH test were randomized. Subjects receiving fluoxetine experienced more improvement in percentage of heartburn-free days (median 35.7, IQR 21.4-57.1) than those on omeprazole (median 7.14, IQR 0-50, p heartburn-free days (median improvement, 57.1, IQR 35.7-57.1 vs 13.9, IQR, 0-45.6 and 7.14, 0-23.8, respectively, p heartburn and normal endoscopy who failed once daily PPIs. The superiority of fluoxetine was mostly attributed to those with normal esophageal pH rather than those with abnormal pH (ClinicalTrials.gov, number NCT01269788). © 2014 John Wiley & Sons Ltd.

  4. An observational study evaluating tacrolimus dose, exposure, and medication adherence after conversion from twice- to once-daily tacrolimus in liver and kidney transplant recipients.

    Bäckman, Lars; Persson, Carl-Axel

    2014-03-17

    Immunosuppression regimens in transplantation medicine are complex. Drugs with extended release action have simplified medication dosing without affecting efficacy. This prospective, observational, multicenter study, conducted in a routine medical practice setting, evaluated changes in tacrolimus daily dose and trough levels and patient-reported medication adherence at day 90 after 1:1 (mg: mg) conversion to once-daily tacrolimus in adult liver and kidney transplant recipients. Data from 224 recipients of a liver (n=19) or kidney (n=205) transplant, average age 51±14.5 years, were evaluated. The mean change in tacrolimus daily dose was +0.04 mg/day. Dose remained stable after conversion in 62.5%, was lower in 15.6%, and higher in 22% of patients. Trough level after conversion was lower in 62.6% and higher in 36.5%; generally, levels were 12.8% lower than pre-conversion levels. No acute rejection, graft loss, or serious safety events were observed. Two deaths occurred due to myocardial infarction. Conversion helped 19% to less frequently forget medications and 55% reported no difference in remembering to take the once-daily dose after conversion. The change in dosing frequency was identified as "better" for 55%. Tacrolimus daily dose remained stable while trough levels were significantly lower after conversion to once-daily dosing. Safety and efficacy were maintained; reduced dosing frequency had no apparent influence on patient-reported medication adherence.

  5. Compliance, clinical outcome, and quality of life of patients with stable angina pectoris receiving once-daily betaxolol versus twice daily metoprolol: a randomized controlled trial

    Przemyslaw Kardas

    2007-05-01

    Full Text Available Przemyslaw KardasThe First Department of Family Medicine, Medical University of LodzBackground: A randomized, controlled trial was conducted in an outpatient setting to examine the effect of beta-blocker dosing frequency on patient compliance, clinical outcome, and health-related quality of life in patients with stable angina pectoris.Methods: One hundred and twelve beta-blockers-naive outpatients with stable angina pectoris were randomized to receive betaxolol, 20 mg once daily or metoprolol tartrate, 50 mg twice daily for 8 weeks. The principal outcome measure was overall compliance measured electronically, whereas secondary outcome measures were drug effectiveness and health-related quality of life.Results: The overall compliance was 86.5 ± 21.3% in the betaxolol group versus 76.1 ± 26.3% in the metoprolol group (p < 0.01, and the correct number of doses was taken on 84.4 ± 21.6% and 64.0 ± 31.7% of treatment days, respectively (p < 0.0001. The percentage of missed doses was 14.5 ± 21.5% in the once-daily group and 24.8 ± 26.4% in the twice-daily group (p < 0.01. The percentage of doses taken in the correct time window (58.6% vs 42.0%, p = 0.01, correct interdose intervals (77.4% v 53.1%, p < 0.0001, and therapeutic coverage (85.6% vs 73.7%, p < 0.001 were significantly higher in the once-daily group. Both studied drugs had similar antianginal effectiveness. Health-related quality of life improved in both groups, but this increase was more pronounced in the betaxolol arm in some dimensions.Conclusions: The study demonstrates that patient compliance with once-daily betaxolol is significantly better than with twice daily metoprolol. Similarly, this treatment provides better quality of life. These results demonstrate possible therapeutic advantages of once-daily over twice-daily beta-blockers in the treatment of stable angina pectoris.Keywords: patient compliance, quality of life, stable angina pectoris, randomized controlled trial

  6. Tadalafil once daily in the treatment of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) in men without erectile dysfunction.

    Brock, Gerald; Broderick, Gregory; Roehrborn, Claus G; Xu, Lei; Wong, David; Viktrup, Lars

    2013-11-01

    To assess the safety and efficacy of tadalafil once daily on lower urinary tract symptoms suggestive of clinical benign prostatic hyperplasia (BPH-LUTS) in men without erectile dysfunction (ED). To compare these with effects in men with ED. After a 4-week washout period and 4-week placebo run-in period, 1089 men without ED (n = 338) and with ED (n = 751) were randomly assigned to placebo or tadalafil 5 mg once daily for 12 weeks in three global clinical studies with similar designs. In the pooled dataset, post hoc analyses of covariance assessed the impact and severity of BPH-LUTS using the International Prostate Symptom Score (IPSS) and the BPH Impact Index (BII) and IPSS quality-of-life (IPSS-QoL) subscores. Safety was assessed using treatment-emergent adverse events. The treatment-by-ED-status interaction was used to assess efficacy differences between the with/without ED subgroups. Men without ED were similar in BPH-LUTS severity/previous therapy to men with ED. Tadalafil significantly reduced BPH-LUTS from baseline when compared with placebo in men without ED (IPSS -5.4 vs -3.3, P  0.68). Tadalafil was safe and well tolerated. Tadalafil 5 mg once daily improved BPH-LUTS in men without ED by a magnitude similar to that observed in men with ED. The adverse event profile in men without ED was consistent with that observed in men with ED. © 2013 The Authors. BJU International © 2013 BJU International.

  7. Comparison of once-daily versus twice-weekly terbinafine administration for the treatment of canine Malassezia dermatitis - a pilot study.

    Berger, Darren J; Lewis, Thomas P; Schick, Anthea E; Stone, Richard T

    2012-10-01

    Terbinafine, an allylamine antifungal, is used in pulsatile dose regimens for superficial mycoses in human medicine. To compare the clinical efficacy of twice-weekly versus once-daily terbinafine administration to determine whether preliminary proof-of-concept evidence exists for pulsatile administration of terbinafine in the treatment of canine Malassezia dermatitis and to determine whether twice-weekly treatment results in fewer clinical and owner-perceived adverse events. Twenty client-owned dogs with Malassezia dermatitis. In this randomized, single-blinded clinical trial, dogs were randomly assigned to receive terbinafine (30 mg/kg) either once daily for 21 days (n = 10) or once daily on two consecutive days per week for six doses (n = 10). On day 0 and day 21, a mean yeast count was calculated from eight anatomical locations via adhesive tape-strip cytology, clinical lesion scores were assigned to the same locations, and owners assessed pruritus using a visual analog scale. There was no significant difference between treatment groups with respect to the reduction in mean yeast count (P = 0.343) and clinical lesion scores (P = 0.887). Pruritus measured by visual analog scale was significantly decreased in the twice-weekly treatment group compared with the daily treatment group (P = 0.047). Seven of 20 dogs had a clinically measurable or owner-reported adverse event during treatment that included gastrointestinal disturbances, excessive panting and elevated hepatic enzymes, with no significant difference noted between treatment groups. This pilot study indicates that twice-weekly terbinafine administration may be an effective alternative treatment for canine Malassezia dermatitis and merits further investigation. © 2012 The Authors. Veterinary Dermatology © 2012 ESVD and ACVD.

  8. Postprandial changes in methanogenic and acidogenic bacteria in the rumens of steers fed high- or low-forage diets once daily.

    Leedle, J A; Greening, R C

    1988-01-01

    Four ruminally fistulated Hereford steers (400 kg) were fed two isocaloric diets at 1.5 x maintenance once daily in a repeated measurement crossover experiment. Postprandial changes in hydrogen-oxidizing, carbon dioxide-reducing bacterial groups were monitored. The methanogenic bacterial populations were present at densities of 4 x 10(8) to 8 x 10(8)/g of ruminal contents on either the high- or low-forage diet. Numbers remained constant postprandially on the high-forage diet but showed a dist...

  9. Clinical benefit of fixed-dose dual bronchodilation with glycopyrronium and indacaterol once daily in patients with chronic obstructive pulmonary disease

    Ulrik, Charlotte Suppli

    2014-01-01

    BACKGROUND AND AIM: Long-acting bronchodilators are the preferred option for maintenance therapy of patients with chronic obstructive pulmonary disease (COPD). The aim of this review is to provide an overview of the clinical studies evaluating the clinical efficacy of the once-daily fixed-dose du...... for chronic Obstructive Lung Disease [GOLD] spirometric criteria). Furthermore, a very recent study has shown that fixed-dose indacaterol/glycopyrronium improves exercise endurance time compared with placebo, although no significant difference was observed between fixed-dose indacaterol...

  10. Changes in body weight, blood pressure and selected metabolic biomarkers with an energy-restricted diet including twice daily sweet snacks and once daily sugar-free beverage

    Nickols-Richardson, Sharon M.; Piehowski, Kathryn E.; Metzgar, Catherine J.; Miller, Debra L.; Preston, Amy G.

    2014-01-01

    BACKGROUND/OBJECTIVES The type of sweet snack incorporated into an energy-restricted diet (ERD) may produce differential effects on metabolic improvements associated with body weight (BW) loss. This study compared effects of incorporating either twice daily energy-controlled dark chocolate snacks plus once daily sugar-free cocoa beverage (DC) to non-chocolate snacks plus sugar-free non-cocoa beverage (NC) into an ERD on BW loss and metabolic outcomes. MATERIALS/METHODS In an 18-week randomize...

  11. The efficacy and safety of a novel lipophilic formulation of methimazole for the once daily transdermal treatment of cats with hyperthyroidism.

    Hill, K E; Gieseg, M A; Kingsbury, D; Lopez-Villalobos, N; Bridges, J; Chambers, P

    2011-01-01

    Previous studies on transdermal methimazole have used pluronic lecithin organogel as the vehicle. This might not be the most suitable vehicle for a lipophilic drug, such as methimazole. Once daily transdermal administration of a novel lipophilic formulation of methimazole is as safe and effective as oral carbimazole in treating hyperthyroidism in cats. Forty-five client-owned cats diagnosed with hyperthyroidism. Prospective study. Cats with newly diagnosed, untreated hyperthyroidism were treated with carbimazole (5 mg p.o., q12h) or methimazole (10 mg) applied to the inner pinnae q24h. Cats were examined after 0, 1, 4, 8, and 12 weeks of treatment. Clinical signs, body weight, systolic blood pressure, hematologic, serum biochemical and urine parameters, total serum thyroxine concentrations (TT4), and serum methimazole concentrations were recorded. No significant differences between groups were detected at day 0. Both formulations were effective in treating hyperthyroidism. No significant differences were detected in thyroxine concentrations, body weight, blood pressure, heart rate, alkaline phosphatase, alanine aminotransferase, creatinine, urea, and urine specific gravity (USG) between groups. The serum methimazole concentrations correlated poorly with TT4-concentrations in both groups. In this 12-week trial, once daily application of a novel formulation of transdermal methimazole applied to the pinnae was as effective and safe as twice daily oral carbimazole in the treatment of cats with hyperthyroidism. This novel formulation and transdermal application could have practical advantages to some pet owners. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  12. Use of new once-daily 5-aminosalicylic acid preparations in the treatment of ulcerative colitis: Is there anything new under the sun?

    Lakatos, Peter Laszlo

    2009-04-21

    5-aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents are commercially available, including azobond pro-drugs, as well as delayed- and controlled-release forms of mesalazine. However, poor adherence due to frequent daily dosing and a large number of tablets has been shown to be an important barrier to successful management of patients with UC. Recently, new, once-daily formulations of mesalazine, including the unique multi-matrix delivery system and mesalazine granules, were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC, with a good safety profile comparable to that of other oral mesalazine formulations. In addition, they offer the advantage of a low pill burden and might contribute to increased long-term compliance and treatment success in clinical practice. This editorial summarizes the available literature on the short- and medium-term efficacy and safety of the new once-daily mesalazine formulations.

  13. Bioavailability of oxycodone after administration of a new prolonged-release once-daily tablet formulation in healthy subjects, in comparison to an established twice-daily tablet
.

    Scheidel, Bernhard; Maritz, Martina A; Gschwind, Yves J; Steigerwald, Kerstin; Guth, Volker; Kovacs, Peter; Rey, Helene

    2017-11-01

    To evaluate and to compare the bioavailability, the influence of food intake on the bioavailability, and the safety and tolerability of a newly-developed oxycodone once-daily (OOD) prolonged-release tablet with an established oxycodone twice-daily (OTD) prolonged-release tablet after single-dose administration under fasting or fed conditions as well as after multiple-dose administration. Three single-center, open-label, randomized, balanced, two-treatment, two-period, two-sequence crossover studies were conducted. In each study, 36 healthy volunteers were randomized to receive 10 mg oxycodone daily as OOD (oxycodone HCL 10-mg PR tablets XL (Develco Pharma Schweiz AG, Pratteln, Switzerland); administration of 1 tablet in the morning) or as OTD (reference formulation: oxygesic 5-mg tablets (Mundipharma GmbH, Limburg an der Lahn, Germany); administration of 1 tablet in the morning and 1 tablet in the evening). Tablets were administered once daily or twice daily under fasting conditions (study 1) or under fed conditions (study 2) as well as after multiple-dose administration (study 3). A sufficient number of blood samples were taken for describing plasma profiles and for calculation of pharmacokinetic parameters. Plasma concentrations of oxycodone were determined by LC-MS/MS. Safety and tolerability were monitored and assessed in all three studies. Plasma profiles of OOD reveal sustained concentrations of oxycodone over the complete dosing interval of 24 hours. In comparison to the OTD reference formulation, the OOD test formulation showed a slightly slower increase of concentrations within the absorption phase and similar plasma concentrations at the maximum and at the end of the dosing interval (24 hours). Extent of bioavailability (AUC), maximum plasma concentrations (Cmax), and plasma concentrations at the end of the dosing interval (Cτ,ss,24h) of OOD could be classified as comparable to OTD considering 90% confidence intervals (CIs) and acceptance limits of 80

  14. A Prospective Open-Label Multicentre Trial on the Use of 1 G, Once Daily Ceftriaxone in Lower Respiratory Tract Infections

    Donald E Low

    1994-01-01

    in the study. Clinical cure and clinical improvement were achieved in 64.6 and 28.3% of the evaluable patients. respectively. Relapse of infection occurred in two patients (1.8%. and treatment failure was recorded in six cases (5.3%. Twelve patients (8.8% died clue to reasons unrelated to the sludy treatment. Three adverse event (hives, diarrhea and phlebitis at the injection site were possibly related to the study drug. A cross-Canada in vitro susceptibility surveillance study of bacterial pathogens. frequently the cause of pneumonia. found ceftriaxone to have minimal inhibitory concentrations in 90% of isolates that would support such a dosing regimen. with the exception of Enterobacter species. These rcsults support the use of 1 g, once daily ceftriaxone for the empirical treatment of pneumonia in those patients requiring hospitalization.

  15. A novel once daily microparticulate dosage form comprising lansoprazole to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease: preparation, pharmacokinetic and pharmacodynamic evaluation.

    Alai, Milind; Lin, Wen Jen

    2013-01-01

    The objective of this study was to formulate and evaluate the lansoprazole (LPZ)-loaded microparticles to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease (GERD). The microparticulate delivery system was prepared by solvent evaporation method using Eudragit RS100 as a matrix polymer followed by enteric coated with Eudragit S100 and hydroxypropyl methylcellulose phthalate HP55 using spray drying method. The enteric coated microparticles were stable in gastric pH condition. In vivo pharmacokinetic and pharmacodynamic studies in male Wistar rats demonstrated that enteric coated microparticles sustained release of LPZ and promoted ulcer healing activity. In other words, the microparticulate dosage form provided effective drug concentration for a longer period as compared to conventional extended release dosage form, and showed sufficient anti-acid secretion activity to treat acid related disorders including the enrichment of nocturnal acid breakthrough event based on a once daily administration.

  16. Efficacy and safety of once-daily NVA237 in patients with moderate-to-severe COPD: the GLOW1 trial

    D'Urzo Anthony

    2011-12-01

    Full Text Available Abstract Background NVA237 is a once-daily dry-powder formulation of the long-acting muscarinic antagonist glycopyrronium bromide in development for the treatment of chronic obstructive pulmonary disease (COPD. The glycopyrronium bromide in COPD airways clinical study 1 (GLOW1 evaluated the efficacy, safety and tolerability of NVA237 in patients with moderate-to-severe COPD. Methods Patients with COPD with a smoking history of ≥ 10 pack-years, post-bronchodilator forced expiratory volume in 1 second (FEV1 1/forced vital capacity 1 antagonists permitted in patients stabilized on them prior to study entry. The primary outcome measure was trough FEV1 at Week 12. Results A total of 822 patients were randomized to NVA237 (n = 552 or placebo (n = 270. Least squares mean (± standard error trough FEV1 at Week 12 was significantly higher in patients receiving NVA237 (1.408 ± 0.0105 L, versus placebo (1.301 ± 0.0137 L; treatment difference 108 ± 14.8 mL, p 1 were apparent at the end of Day 1 and sustained through Week 26. FEV1 was significantly improved in the NVA237 group versus placebo throughout the 24-hour periods on Day 1 and at Weeks 12 and 26, and at all other visits and timepoints. Transition dyspnoea index focal scores and St. George's Respiratory Questionnaire scores were significantly improved with NVA237 versus placebo at Week 26, with treatment differences of 1.04 (p Conclusions Once-daily NVA237 was safe and well tolerated and provided rapid, sustained improvements in lung function, improvements in dyspnoea, and health-related quality of life, and reduced the risk of exacerbations and the use of rescue medication. Trial registration ClinicalTrials.gov: NCT01005901

  17. Lansoprazole 15 mg once daily for 14 days is effective for treatment of frequent heartburn: results of 2 randomized, placebo-controlled, double-blind studies.

    Kushner, Pamela R; Snoddy, Andrew M; Gilderman, Larry; Peura, David A

    2009-07-01

    To investigate the efficacy and safety of a 14-day treatment period with lansoprazole 15 mg for frequent heartburn in patients who are likely to select a nonprescription medication before consulting a prescriber. Adults with untreated frequent heartburn > or = 2 days a week over the past month were recruited for 2 identical multicenter, double-blind studies conducted with a 1-week screening and heartburn medication washout, a 1-week placebo run-in, a 2-week placebo-controlled treatment, and a 1-week placebo follow-up. After the washout and placebo run-in, subjects were randomly assigned to receive lansoprazole 15 mg or placebo once daily for 14 days in a double-blind fashion. Antacid tablets were permitted as rescue medication. Endpoints included percentage of 24-hour days without heartburn (primary), percentage of night-times without heartburn, and percentage of subjects without heartburn during day 1 of treatment (secondary endpoints). Data were collected daily via an interactive voice response system. In studies 1 and 2, 282 and 288 subjects, respectively, were randomly assigned to lansoprazole, and 282 in each study received placebo. The mean percentage of days without heartburn was greater among lansoprazole recipients compared with placebo recipients (P heartburn and no heartburn during day 1 of the 14-day treatment. Adverse events were infrequent and were similar for lansoprazole and placebo groups. During the 14-day treatment period in a population with frequent heartburn who were likely to select a medication without consulting a prescriber, lansoprazole 15 mg once daily showed rapid and sustained effectiveness throughout a 24-hour period and was well tolerated.

  18. Legal, ethical, and economic implications of breaking down once-daily fixed-dose antiretroviral combinations into their single components for cost reduction.

    Ramiro, Miguel A; Llibre, Josep M

    2014-11-01

    The availability of generic lamivudine in the context of the current economic crisis has raised a new issue in some European countries: breaking up the once-daily fixed-dose antiretroviral combinations (FDAC) of efavirenz/tenofovir/emtricitabine, tenofovir/emtricitabine, or abacavir/lamivudine, in order to administer their components separately, thereby allowing the use of generic lamivudine instead of branded emtricitabine or lamivudine. The legal, ethical, and economic implications of this potential strategy are reviewed, particularly in those patients receiving a once-daily single-tablet regimen. An unfamiliar change in antiretroviral treatment from a successful patient-friendly FDAC into a more complex regimen including separately the components to allow the substitution of one (or some) of them for generic surrogates (in the absence of a generic bioequivalent FDAC) could be discriminatory because it does not guarantee access to equal excellence in healthcare to all citizens. Furthermore, it could violate the principle of non-maleficence by potentially causing harm both at the individual level (hindering adherence and favouring treatment failure and resistance), and at the community level (hampering control of disease transmission and transmission of HIV-1 resistance). Replacing a FDAC with the individual components of that combination should only be permitted when the substituting medication has the same qualitative and quantitative composition of active ingredients, pharmaceutical form, method of administration, dosage and presentation as the medication being replaced, and a randomized study has demonstrated its non-inferiority. Finally, a strict pharma-economic study supporting this change, comparing the effectiveness and the cost of a specific intervention with the best available alternative, should be undertaken before its potential implementation. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiolog

  19. Randomised clinical trial: alginate (Gaviscon Advance) vs. placebo as add-on therapy in reflux patients with inadequate response to a once daily proton pump inhibitor.

    Reimer, C; Lødrup, A B; Smith, G; Wilkinson, J; Bytzer, P

    2016-04-01

    Many reflux patients remain symptomatic on a standard dose of proton pump inhibitor (PPI). Alginates decrease the number of reflux events by forming a raft on top of the stomach content and thus offer a supplemental mechanism of action to acid suppression. To assess the efficacy of an alginate (Gaviscon Advance, Reckitt Benckiser, Slough, UK) on reflux symptoms in patients with persistent symptoms despite once daily PPI. This was a multicentre, randomised, placebo-controlled, 7-day double-blind trial preceded by a 7-day run-in period. Reflux symptoms were assessed using the Heartburn Reflux Dyspepsia Questionnaire (HRDQ). Based on symptom score during run-in, eligible patients were randomised to Gaviscon Advance 10 mL four times a day or placebo in addition to a once daily PPI. The primary endpoint was change in HRDQ score post-treatment compared to baseline. One hundred and thirty-six patients were randomised. Change in HRDQ reflux score was significantly greater for Gaviscon Advance (mean: -5.0, s.d.: 4.7) than for placebo (mean: -3.5, s.d.: 5.5) with an LS mean difference of 1.6 [95% CI -3.1 to -0.1], P = 0.03. A decrease in the mean (s.d.) number of nights with symptoms was observed from 3.6 (2.8) to 3.0 (3.0) in the placebo group and from 3.9 (2.8) to 2.2 (2.7) for the Gaviscon Advance group. This reduction was significantly greater in the Gaviscon Advance group than in the placebo group [LS mean difference = -0.9, 95% CI (-1.6 to -0.2), P < 0.01]. In patients with residual reflux symptoms despite PPI treatment, adding an alginate offers additional decrease in the burden of reflux symptoms (EudraCT/IND Number: 2011-005486-21). © 2016 John Wiley & Sons Ltd.

  20. Exploratory study of once-daily transcranial direct current stimulation (tDCS) as a treatment for auditory hallucinations in schizophrenia.

    Fröhlich, F; Burrello, T N; Mellin, J M; Cordle, A L; Lustenberger, C M; Gilmore, J H; Jarskog, L F

    2016-03-01

    Auditory hallucinations are resistant to pharmacotherapy in about 25% of adults with schizophrenia. Treatment with noninvasive brain stimulation would provide a welcomed additional tool for the clinical management of auditory hallucinations. A recent study found a significant reduction in auditory hallucinations in people with schizophrenia after five days of twice-daily transcranial direct current stimulation (tDCS) that simultaneously targeted left dorsolateral prefrontal cortex and left temporo-parietal cortex. We hypothesized that once-daily tDCS with stimulation electrodes over left frontal and temporo-parietal areas reduces auditory hallucinations in patients with schizophrenia. We performed a randomized, double-blind, sham-controlled study that evaluated five days of daily tDCS of the same cortical targets in 26 outpatients with schizophrenia and schizoaffective disorder with auditory hallucinations. We found a significant reduction in auditory hallucinations measured by the Auditory Hallucination Rating Scale (F2,50=12.22, PtDCS for treatment of auditory hallucinations and the pronounced response in the sham-treated group in this study contrasts with the previous finding and demonstrates the need for further optimization and evaluation of noninvasive brain stimulation strategies. In particular, higher cumulative doses and higher treatment frequencies of tDCS together with strategies to reduce placebo responses should be investigated. Additionally, consideration of more targeted stimulation to engage specific deficits in temporal organization of brain activity in patients with auditory hallucinations may be warranted. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  1. Once daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study.

    Arnold, Lesley M; Arsenault, Pierre; Huffman, Cynthia; Patrick, Jeffrey L; Messig, Michael; Chew, Marci L; Sanin, Luis; Scavone, Joseph M; Pauer, Lynne; Clair, Andrew G

    2014-10-01

    Safety and efficacy of a once daily controlled-released (CR) formulation of pregabalin was evaluated in patients with fibromyalgia using a placebo-controlled, randomized withdrawal design. This multicenter study included 6 week single-blind pregabalin CR treatment followed by 13 week double-blind treatment with placebo or pregabalin CR. The starting dose of 165 mg/day was escalated during the first 3 weeks, up to 495 mg/day based on efficacy and tolerability. Patients with ≥50% reduction in average daily pain score at the end of the single-blind phase were randomized to continue pregabalin CR at the optimized dose (330-495 mg/day) or to placebo. The primary endpoint was time to loss of therapeutic response (LTR), defined as treatment' (Benefit, Satisfaction, and Willingness to Continue Scale) in the pregabalin CR group; no other secondary endpoints were statistically significant. Most AEs were mild to moderate in severity (most frequent: dizziness, somnolence). The percentage of pregabalin CR patients discontinuing because of AEs was 12.2% and 4.8% in the single-blind and double-blind phases, respectively (placebo, 0%). Time to LTR was significantly longer with pregabalin CR versus placebo in fibromyalgia patients who initially showed improvement with pregabalin CR, indicating maintenance of response. Pregabalin CR was well tolerated in most patients. Generalizability may be limited by study duration and selective population.

  2. Review of Efficacy and Safety of Duloxetine 40 to 60 mg Once Daily in Patients with Diabetic Peripheral Neuropathic Pain

    Vladimir Skljarevski

    2012-01-01

    Full Text Available We summarize efficacy and safety findings from 4 double-blind, placebo-controlled, 12-week studies and 1 open-label, uncontrolled, 34-week maintenance-of-effect (MOE study that examine duloxetine 40 and 60 mg once daily (QD in patients with diabetic peripheral neuropathic pain (DPNP. In all placebo-controlled studies, duloxetine showed significantly (P≤.01 greater reduction in pain severity (weekly mean of 24-hour average pain severity ratings, primary outcome measure compared with placebo. In all placebo-controlled studies, duloxetine showed significantly (P≤.05 greater improvement on brief pain inventory-Interference ratings. Patient global impression of improvement ratings were superior to placebo (P≤.01 for duloxetine patients in all placebo-controlled studies. Response rates (based on 30% pain reduction ranged from 57% to 68% for duloxetine and from 35% to 47% for placebo and were statistically significantly different (P≤.01 between treatment groups in 3 out of 4 studies. The open-label study showed maintenance of analgesic effect of duloxetine in DPNP. In the duloxetine groups, 4.3% to 14.9% of patients discontinued because of adverse events (placebo groups: 2.6% to 7.4%. Most commonly reported treatment-emergent adverse events were nausea, somnolence, and headache. Duloxetine 40 and 60 mg QD was efficacious and well tolerated in the management of DPNP.

  3. Efficacy and Safety of Once-Daily Minoxidil Foam 5% Versus Twice-Daily Minoxidil Solution 2% in Female Pattern Hair Loss: A Phase III, Randomized, Investigator-Blinded Study.

    Blume-Peytavi, Ulrike; Shapiro, Jerry; Messenger, Andrew G; Hordinsky, Maria K; Zhang, Paul; Quiza, Carlos; Doshi, Uday; Olsen, Elise A

    2016-07-01

    A once-daily minoxidil topical foam (MTF) has been developed to treat female pattern hair loss. Determine noninferiority of once-daily 5% MTF versus twice-daily 2% minoxidil topical solution (MTS) based on the change from baseline in target area hair count (TAHC) at 24 weeks. In a randomized, phase III trial, women with female pattern hair loss received once-daily 5% MTF (n=161) or twice-daily 2% MTS (n=161) for 52 weeks. Primary endpoint was change from baseline in TAHC at 24 weeks. Secondary endpoint was change from baseline in TAHC at 12 weeks. Exploratory endpoints included change in total unit area density and change in overall scalp coverage. Once-daily 5% MTF increased TAHC from baseline (adjusted mean ± standard error) by 23.9 ± 2.1 hairs/cm2 at week 24. Twice-daily 2% MTS increased TAHC 24.2 ± 2.1 hairs/cm2 at week 24. The treatment difference was -0.3 hairs/cm2 (95% CI = -6.0, 5.4). Since the lower bound of the 95% CI was less than -5.0, the prespecified noninferiority goal was not met. Both treatments were well tolerated. Once-daily 5% MTF and twice-daily 2% MTS induced hair regrowth in female pattern hair loss, but prespecified noninferiority criteria were not met. ClinicalTrials.gov identifier: NCT01145625 J Drugs Dermatol. 2016;15(7):883-889.

  4. Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide

    Chen, Jing; Mo, Yiqun; Schlueter, Connie F.; Hoyle, Gary W., E-mail: Gary.Hoyle@louisville.edu

    2013-10-15

    Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-induced neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1 h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6 h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury. - Highlights: • Chlorine causes lung injury when inhaled and is considered a chemical threat agent. • Corticosteroids may inhibit lung injury through their anti-inflammatory actions. • Corticosteroids inhibited chlorine-induced pneumonitis and pulmonary edema. • Mometasone and budesonide are potential rescue treatments for chlorine lung injury.

  5. Efficacy and safety of coadministration of once-daily indacaterol and glycopyrronium versus indacaterol alone in COPD patients: the GLOW6 study

    Vincken W

    2014-02-01

    Full Text Available Walter Vincken,1 Joseph Aumann,2 Hungta Chen,3 Michelle Henley,3 Danny McBryan,4 Pankaj Goyal4 1Respiratory Division, University Hospital, UZ Brussel, Free University of Brussels, Brussels, Belgium; 2Longartsenpraktijk, Prins Bisschopssingel, Hasselt, Belgium; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 4Novartis Pharma AG, Basel, Switzerland Background: Addition of a second bronchodilator from a different pharmacological class may benefit patients with moderate-to-severe chronic obstructive pulmonary disease (COPD whose symptoms are insufficiently controlled by bronchodilator monotherapy. GLOW6 evaluated the efficacy and safety of once-daily coadministration of the long-acting β2-agonist indacaterol (IND and the long-acting muscarinic antagonist glycopyrronium (GLY versus IND alone in patients with moderate-to-severe COPD. Materials and methods: In this randomized, double-blind, parallel group, placebo-controlled, 12-week study, patients were randomized 1:1 to IND 150 µg and GLY 50 µg daily (IND + GLY or IND 150 µg daily and placebo (IND + PBO (all delivered via separate Breezhaler® devices. The primary objective was to demonstrate the superiority of IND + GLY versus IND + PBO for trough forced expiratory volume in 1 second (FEV1 at week 12. Other end points included trough FEV1 at day 1, FEV1 area under the curve from 30 minutes to 4 hours (AUC30min–4h, peak FEV1, inspiratory capacity and trough forced vital capacity (FVC at day 1 and week 12, and transition dyspnea index (TDI focal score, COPD symptoms, and rescue medication use over 12 weeks. Results: A total of 449 patients were randomized (IND + GLY, 226; IND + PBO, 223; 94% completed the study. On day 1 and at week 12, IND + GLY significantly improved trough FEV1 versus IND + PBO, with treatment differences of 74 mL (95% CI 46–101 mL and 64 mL (95% CI 28–99 mL, respectively (both P<0.001. IND + GLY significantly improved postdose peak FEV1, FEV1 AUC30min–4h

  6. Cost effectiveness of once-daily oral chelation therapy with deferasirox versus infusional deferoxamine in transfusion-dependent thalassaemia patients: US healthcare system perspective.

    Delea, Thomas E; Sofrygin, Oleg; Thomas, Simu K; Baladi, Jean-Francois; Phatak, Pradyumna D; Coates, Thomas D

    2007-01-01

    Deferasirox is a recently approved once-daily oral iron chelator that has been shown to reduce liver iron concentrations and serum ferritin levels to a similar extent as infusional deferoxamine. To determine the cost effectiveness of deferasirox versus deferoxamine in patients with beta-thalassaemia major from a US healthcare system perspective. A Markov model was used to estimate the total additional lifetime costs and QALYs gained with deferasirox versus deferoxamine in patients with beta-thalassaemia major and chronic iron overload from blood transfusions. Patients were assumed to be 3 years of age at initiation of chelation therapy and to receive prescribed dosages of deferasirox and deferoxamine that have been shown to be similarly effective in such patients. Compliance with chelation therapy and probabilities of iron overload-related cardiac disease and death by degree of compliance were estimated using data from published studies. Costs ($US, year 2006 values) of deferoxamine administration and iron overload-related cardiac disease were based on analyses of health insurance claims of transfusion-dependent thalassaemia patients. Utilities were based on a study of patient preferences for oral versus infusional chelation therapy, as well as published literature. Probabilistic and deterministic sensitivity analyses were employed to examine the robustness of the results to key assumptions. Deferasirox resulted in a gain of 4.5 QALYs per patient at an additional expected lifetime cost of $US126,018 per patient; the cost per QALY gained was $US28,255. The cost effectiveness of deferasirox versus deferoxamine was sensitive to the estimated costs of deferoxamine administration and the quality-of-life benefit associated with oral versus infusional therapy. Cost effectiveness was also relatively sensitive to the equivalent daily dose of deferasirox, and the unit costs of deferasirox and deferoxamine, and was more favourable in younger patients. Results of this analysis

  7. Fosamprenavir or atazanavir once daily boosted with ritonavir 100 mg, plus tenofovir/emtricitabine, for the initial treatment of HIV infection: 48-week results of ALERT

    Ross Lisa L

    2008-03-01

    Full Text Available Abstract Background Once-daily (QD ritonavir 100 mg-boosted fosamprenavir 1400 mg (FPV/r100 or atazanavir 300 mg (ATV/r100, plus tenofovir/emtricitabine (TDF/FTC 300 mg/200 mg, have not been compared as initial antiretroviral treatment. To address this data gap, we conducted an open-label, multicenter 48-week study (ALERT in 106 antiretroviral-naïve, HIV-infected patients (median HIV-1 RNA 4.9 log10 copies/mL; CD4+ count 191 cells/mm3 randomly assigned to the FPV/r100 or ATV/r100 regimens. Results At baseline, the FPV/r100 or ATV/r100 arms were well-matched for HIV-1 RNA (median, 4.9 log10 copies/mL [both], CD4+ count (mean, 176 vs 205 cells/mm3. At week 48, intent-to-treat: missing/discontinuation = failure analysis showed similar responses to FPV/r100 and ATV/r100 (HIV-1 RNA 3, p = 0.398 [Wilcoxon rank sum test]. Fasting total/LDL/HDL-cholesterol changes-from-baseline were also similar, although week 48 median fasting triglycerides were higher with FPV/r100 (150 vs 131 mg/dL. FPV/r100-treated patients experienced fewer treatment-related grade 2–4 adverse events (15% vs 57%, with differences driven by ATV-related hyperbilirubinemia. Three patients discontinued TDF/FTC because their GFR decreased to Conclusion The all-QD regimens of FPV/r100 and ATV/r100, plus TDF/FTC, provided similar virologic, CD4+ response, and fasting total/LDL/HDL-cholesterol changes through 48 weeks. Fewer FPV/r100-treated patients experienced treatment-related grade 2–4 adverse events.

  8. Concentrations of dapivirine in the rhesus macaque and rabbit following once daily intravaginal administration of a gel formulation of [14C]dapivirine for 7 days.

    Nuttall, Jeremy P; Thake, Daryl C; Lewis, Mark G; Ferkany, John W; Romano, Joseph W; Mitchnick, Mark A

    2008-03-01

    Dapivirine is a nonnucleoside reverse transcriptase inhibitor being developed as a topical microbicide for the prevention of human immunodeficiency virus infection. The distribution of radioactivity and drug in plasma and in vaginal, cervical, and draining lymph node tissues was investigated after daily application of a vaginal gel formulation of [14C]dapivirine to rhesus macaques. This was preceded by a preliminary study with rabbits. Following the intravaginal administration of [14C]dapivirine ( approximately 0.1 mg/ml [15 microCi/ml]) to rabbits (0.5 ml/day) and macaques (1 ml/day) for 7 days, the dapivirine levels associated with vaginal and cervical tissue samples 1 h after the final dose were high (quantities of microg/g of tissue) and remained detectable at 24 h (mean, >or=2.5 ng/g in rabbits) and 48 h (mean, >80 ng/g in macaques). Radioactivity levels were low in the plasma and very low or unquantifiable in the draining lymph nodes of the macaques. Microautoradiography identified drug-related material (DRM) on the surfaces of the vaginal and cervical tissues of the rabbits and macaques. Although DRM was primarily associated with the outermost layer of shedding cells in rabbits, two animals showed some evidence of small quantities in the mucosal epithelium of the cervix. In macaques, DRM was seen within the keratinized layer of the vaginal epithelium and and was found to extend into the superficial cellular layers, and in at least one animal it appeared to be present in the deepest (germinal) layer of the epithelium and in submucosal tissues. The persistence of biologically significant concentrations of dapivirine in vaginal and cervical tissues for >24 h supports the development of dapivirine as a microbicide for once daily application.

  9. Concentrations of Dapivirine in the Rhesus Macaque and Rabbit following Once Daily Intravaginal Administration of a Gel Formulation of [14C]Dapivirine for 7 Days▿

    Nuttall, Jeremy P.; Thake, Daryl C.; Lewis, Mark G.; Ferkany, John W.; Romano, Joseph W.; Mitchnick, Mark A.

    2008-01-01

    Dapivirine is a nonnucleoside reverse transcriptase inhibitor being developed as a topical microbicide for the prevention of human immunodeficiency virus infection. The distribution of radioactivity and drug in plasma and in vaginal, cervical, and draining lymph node tissues was investigated after daily application of a vaginal gel formulation of [14C]dapivirine to rhesus macaques. This was preceded by a preliminary study with rabbits. Following the intravaginal administration of [14C]dapivirine (∼0.1 mg/ml [15 μCi/ml]) to rabbits (0.5 ml/day) and macaques (1 ml/day) for 7 days, the dapivirine levels associated with vaginal and cervical tissue samples 1 h after the final dose were high (quantities of μg/g of tissue) and remained detectable at 24 h (mean, ≥2.5 ng/g in rabbits) and 48 h (mean, >80 ng/g in macaques). Radioactivity levels were low in the plasma and very low or unquantifiable in the draining lymph nodes of the macaques. Microautoradiography identified drug-related material (DRM) on the surfaces of the vaginal and cervical tissues of the rabbits and macaques. Although DRM was primarily associated with the outermost layer of shedding cells in rabbits, two animals showed some evidence of small quantities in the mucosal epithelium of the cervix. In macaques, DRM was seen within the keratinized layer of the vaginal epithelium and and was found to extend into the superficial cellular layers, and in at least one animal it appeared to be present in the deepest (germinal) layer of the epithelium and in submucosal tissues. The persistence of biologically significant concentrations of dapivirine in vaginal and cervical tissues for >24 h supports the development of dapivirine as a microbicide for once daily application. PMID:18086845

  10. Pharmacokinetics, safety and efficacy of ritonavir-boosted atazanavir (300/100 mg once daily) in HIV-1-infected pregnant women.

    Lê, Minh P; Mandelbrot, Laurent; Descamps, Diane; Soulié, Cathia; Ichou, Houria; Bourgeois-Moine, Agnès; Damond, Florence; Lariven, Sylvie; Valantin, Marc-Antoine; Landman, Roland; Faucher, Philippe; Tubiana, Roland; Duro, Dominique; Meier, Françoise; Legac, Sylvie; Bourse, Patricia; Mortier, Emmanuel; Dommergues, Marc; Calvez, Vincent; Matheron, Sophie; Peytavin, Gilles

    2015-01-01

    Atazanavir/ritonavir (ATV/r) is a boosted protease inhibitor recommended to minimize the risk of mother-to-child HIV-1 transmission (MTCT). We aimed to assess the pharmacokinetics, safety and efficacy of ATV/r in HIV-1-infected pregnant women and their neonates. A multicentre, cross-sectional, non-interventional cohort of HIV-1-infected pregnant women receiving ATV/r (300/100 mg once daily) who delivered in three Paris hospitals from 2006 to 2013 was designed. We determined antiretroviral trough plasma concentrations using liquid chromatography-mass spectrometry at each of the three trimesters, delivery and post-partum. ATV concentrations at 24 h (C24h) were interpreted by the 150-850 ng/ml efficacy-tolerance thresholds. Safety data and newborn HIV status were recorded. A mother's virological failure was defined as two successive measurements of plasma HIV-1 RNA>50 copies/ml within the 2 months before delivery. 103 pregnant women were included, mostly from sub-Saharan Africa (88%). ATV C24h at each of the three trimesters and delivery remained similar to post-partum values. No dose adjustment was needed during pregnancy. The median plasma ratio of fetal/maternal ATV level was 0.19 (n=28). Only three patients showed two successive detectable viral loads but <400 copies/ml. Among 82 available newborn data, 16 were born preterm. Three in utero deaths occurred. Tolerance was good with one case of maternal grade 3 hyperbilirubinaemia, no cases in neonates at delivery and no clinically relevant adverse event. No case of MTCT was reported. In this population, an ATV/r-containing antiretroviral regimen demonstrated good pharmacokinetics, virological efficacy and safety. No significant impact of pregnancy on ATV C24h was found. No dose adjustment was required.

  11. Extended-Release Once-Daily Formulation of Tofacitinib: Evaluation of Pharmacokinetics Compared With Immediate-Release Tofacitinib and Impact of Food.

    Lamba, Manisha; Wang, Rong; Fletcher, Tracey; Alvey, Christine; Kushner, Joseph; Stock, Thomas C

    2016-11-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. An extended-release (XR) formulation has been designed to provide a once-daily (QD) dosing option to patients to achieve comparable pharmacokinetic (PK) parameters to the twice-daily immediate-release (IR) formulation. We conducted 2 randomized, open-label, phase 1 studies in healthy volunteers. Study A characterized single-dose and steady-state PK of tofacitinib XR 11 mg QD and intended to demonstrate equivalence of exposure under single-dose and steady-state conditions to tofacitinib IR 5 mg twice daily. Study B assessed the effect of a high-fat meal on the bioavailability of tofacitinib from the XR formulation. Safety and tolerability were monitored in both studies. In study A (N = 24), the XR and IR formulations achieved time to maximum plasma concentration at 4 hours and 0.5 hours postdose, respectively; terminal half-life was 5.9 hours and 3.2 hours, respectively. Area under plasma concentration-time curve (AUC) and maximum plasma concentration (C max ) after single- and multiple-dose administration were equivalent between the XR and IR formulations. In study B (N = 24), no difference in AUC was observed for fed vs fasted conditions. C max increased by 27% under the fed state. On repeat administration, negligible accumulation (Tofacitinib administration as an XR or IR formulation was generally well tolerated in these studies. © 2016, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  12. Once-daily long-acting beta-agonists for chronic obstructive pulmonary disease: an indirect comparison of olodaterol and indacaterol

    Roskell NS

    2014-07-01

    Full Text Available Neil S Roskell,1 Antonio Anzueto,2 Alan Hamilton,3 Bernd Disse,4 Karin Becker5 1Statistics, Bresmed Health Solutions Ltd, Sheffield, UK; 2School of Medicine, University of Texas Health Science Center, San Antonio, TX, USA; 3Medical Department, Boehringer Ingelheim (Canada Ltd, Burlington, ON, Canada; 4Medical Department, Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany; 5Global Health Economics and Outcomes Research, Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany Purpose: In the absence of head-to-head clinical trials comparing the once-daily, long-acting beta2-agonists olodaterol and indacaterol for the treatment of chronic obstructive pulmonary disease (COPD, an indirect treatment comparison by systematic review and synthesis of the available clinical evidence was conducted. Methods: A systematic literature review of randomized, controlled clinical trials in patients with COPD was performed to evaluate the efficacy and safety of olodaterol and indacaterol. Network meta-analysis and adjusted indirect comparison methods were employed to evaluate treatment efficacy, using outcomes based on trough forced expiratory volume in 1 second (FEV1, Transition Dyspnea Index, St George’s Respiratory Questionnaire total score and response, rescue medication use, and proportion of patients with exacerbations. Results: Eighteen trials were identified for meta-analysis (eight, olodaterol; ten, indacaterol. Olodaterol trials included patients of all severities, whilst indacaterol trials excluded patients with very severe COPD. Concomitant maintenance bronchodilator use was allowed in most olodaterol trials, but not in indacaterol trials. When similarly designed trials/data were analyzed for change from baseline in trough FEV1 (liters, the following mean differences (95% confidence interval were observed: trials excluding concomitant bronchodilator: indacaterol 75 mcg versus olodaterol 5 mcg, –0.005 (–0.077 to 0.067, and indacaterol 150 mcg

  13. Once-daily milking during a feed deficit decreases milk production but improves energy status in early lactating grazing dairy cows.

    Kay, J K; Phyn, C V C; Rius, A G; Morgan, S R; Grala, T M; Roche, J R

    2013-10-01

    The objective of this study was to investigate the effect of milking frequency (MF) at 2 feeding levels (FL) on milk production, body condition score, and metabolic indicators of energy status in grazing dairy cows during early lactation. Multiparous Holstein-Friesian and Holstein-Friesian × Jersey cows (n=120) grazed pasture and were milked twice daily (2×) from calving until 34 ± 6 d in milk (mean ± standard deviation). Cows were then allocated to 1 of 4 treatments in a 2 × 2 factorial arrangement. Treatments consisted of 2 FL: adequately fed [AF; 14.3 kg dry matter intake (DMI)/cow per d] or underfed (UF; 8.3 kg of DMI/cow per d) and 2 MF: 2× or once daily (1×). Treatments were imposed for 3 wk. After the treatment period, all cows were offered a generous pasture allowance (grazing residuals >1,600 kg of dry matter/ha) and milked 2×. During the 3-wk treatment period, we observed an interaction between FL and MF for energy-corrected milk (ECM), such that the decrease due to 1× milking was greater in AF than in UF cows (20 and 14% decrease, respectively). No interactions were found posttreatment. Cows previously UF produced 7% less ECM than AF cows during wk 4 to 12; however, no subsequent effect was observed of the previous underfeeding. Cows previously milked 1× produced 5% less ECM during wk 4 to 12, and differences remained during wk 13 to 23. During the 3-wk treatment period, UF cows lost 0.2 body condition score units (1-10 scale) and this was not affected by 1× milking. During the treatment period, UF cows had lower plasma glucose, insulin, and insulin-like growth factor I, and greater nonesterified fatty acids and β-hydroxybutyrate concentrations than AF cows. Cows milked 1× had greater plasma glucose, insulin, and insulin-like growth factor I, and lower nonesterified fatty acids and β-hydroxybutyrate concentrations compared with cows milked 2×. In conclusion, energy status was improved by 1× milking; however, when UF cows were milked 1

  14. Effectiveness and gastrointestinal tolerability during conversion and titration with once-daily OROS® hydromorphone extended release in opioid-tolerant patients with chronic low back pain

    Hale, Martin E; Nalamachu, Srinivas R; Khan, Arif; Kutch, Michael

    2013-01-01

    Purpose To describe the efficacy and safety of hydromorphone extended-release tablets (OROS hydromorphone ER) during dose conversion and titration. Patients and methods A total of 459 opioid-tolerant adults with chronic moderate to severe low back pain participated in an open-label, 2- to 4-week conversion/titration phase of a double-blind, placebo-controlled, randomized withdrawal trial, conducted at 70 centers in the United States. Patients were converted to once-daily OROS hydromorphone ER at 75% of the equianalgesic dose of their prior total daily opioid dose (5:1 conversion ratio), and titrated as frequently as every 3 days to a maximum dose of 64 mg/day. The primary outcome measure was change in pain intensity numeric rating scale; additional assessments included the Patient Global Assessment and the Roland–Morris Disability Questionnaire scores. Safety assessments were performed at each visit and consisted of recording and monitoring all adverse events (AEs) and serious AEs. Results Mean (standard deviation) final daily dose of OROS hydromorphone ER was 37.5 (17.8) mg. Mean (standard error of the mean [SEM]) numeric rating scale scores decreased from 6.6 (0.1) at screening to 4.3 (0.1) at the final titration visit (mean [SEM] change, −2.3 [0.1], representing a 34.8% reduction). Mean (SEM) change in Patient Global Assessment was −0.6 (0.1), and mean change (SEM) in the Roland–Morris Disability Questionnaire was −2.8 (0.3). Patients achieving a stable dose showed greater improvement than patients who discontinued during titration for each of these measures (P < 0.001). Almost 80% of patients achieving a stable dose (213/268) had a ≥30% reduction in pain. Commonly reported AEs were constipation (15.4%), nausea (11.9%), somnolence (8.7%), headache (7.8%), and vomiting (6.5%); 13.0% discontinued from the study due to AEs. Conclusion The majority of opioid-tolerant patients with chronic low back pain were successfully converted to effective doses of

  15. Pilot study of once-daily simplification therapy with abacavir/lamivudine/zidovudine and efavirenz for treatment of HIV-1 infection.

    Ruane, Peter; Lang, Joseph; DeJesus, Edwin; Berger, Daniel S; Dretler, Robin; Rodriguez, Allan; Ward, Douglas J; Lim, Michael L; Liao, Qiming; Reddy, Sunila; Clair, Marty St; Vila, Tania; Shaefer, Mark S

    2006-01-01

    The purpose of this pilot study was to explore the efficacy and safety of the abacavir/lamivudine/zidovudine fixed-dose combination tablet administered as two tablets once daily (qd) versus one tablet twice daily (bid) in combination with efavirenz (EFV). This was a prospective, randomized, open-label, multicenter study with a 24-week treatment period in 7 outpatient HIV clinics in the United States. Patients currently receiving an initial regimen of abacavir/lamivudine/zidovudine bid plus EFV qd for at least 6 months with HIV-1 RNA or = 200 cells/mm3 were eligible. Thirty-six patients enrolled, and 35 (97%) completed the study. Participants were randomized to switch to 2 tablets of abacavir/lamivudine/zidovudine qd plus EFV qd (QD arm) or continue current treatment (BID arm) for 24 weeks. Efficacy, safety, and adherence were evaluated. Median baseline CD4+ cell count was 521 cells/mm3. At week 24, HIV-1 RNA or = 0.29 to +0.18, p = 1.000). At week 24, median CD4+ cell count change from baseline was +26 cells/mm3 for the QD arm and -39 cells/mm3 for BID arm. One patient randomized to the QD arm met virologic failure criteria (confirmed HIV-1 RNA >120 copies/mL) at week 20 and viral genotype showed M184V. After failure, this patient revealed he never took EFV throughout the entire study after randomization, effectively receiving only abacavir/lamivudine/zidovudine qd alone. Median adherence was slightly higher in the QD arm, although both arms had broad variability and overlapping interquartile ranges. Adverse events were infrequent and occurred with similar frequency between arms; treatment-related adverse events were abdominal pain, flatulence, nausea, headache, and abnormal dreams (1 patient [3%] for each adverse event). No patients withdrew due to adverse events, and no abacavir hypersensitivity reactions were reported. In this pilot study of patients suppressed on abacavir/lamivudine/zidovudine bid plus EFV, 94% of participants switching to abacavir

  16. Real-world glycemic outcomes in patients with type 2 diabetes initiating exenatide once weekly and liraglutide once daily: a retrospective cohort study

    Saunders WB

    2016-07-01

    Full Text Available William B Saunders,1 Hiep Nguyen,2 Iftekhar Kalsekar2 1Department of Public Health Sciences, College of Health and Human Services, The University of North Carolina at Charlotte, Charlotte, NC, 2AstraZeneca, Fort Washington, PA, USA Aim: The glucagon-like peptide-1 receptor agonists exenatide once weekly (QW and liraglutide once daily (QD have demonstrated improvements in glycemic outcomes in patients with type 2 diabetes mellitus in randomized clinical trials. However, little is known about their real-world comparative effectiveness. This retrospective cohort study used the Quintiles Electronic Medical Record database to evaluate the 6-month change in glycated hemoglobin (A1C for patients initiating exenatide QW or liraglutide QD.Methods: Patients with type 2 diabetes mellitus prescribed exenatide QW (n=664 or liraglutide QD (n=3,283 between February 1, 2012 and May 31, 2013 were identified. Baseline A1C measures were from 75 days before to 15 days after initiating exenatide QW or liraglutide QD, with follow-up measures documented at 6 months (±45 days. Adjusted linear regression models compared the difference in mean A1C change. A priori defined sensitivity analysis was performed in the subgroup of patients with baseline A1C ≥7.0% and no prescription for insulin during the 12-month pre-index period.Results: For exenatide QW and liraglutide QD, respectively, mean (SD age of the main study cohort was 58.01 (10.97 and 58.12 (11.05 years, mean (SD baseline A1C was 8.4% (1.6 and 8.4% (1.6, and 48.2% and 54.2% of patients were women. In adjusted models, change in A1C did not differ between exenatide QW and liraglutide QD during 6 months of follow-up. Results were consistent in the subgroup analyses.Conclusion: In a real-world setting, A1C similarly improves in patients initiating exenatide QW or liraglutide QD. Keywords: diabetes, exenatide, outcomes

  17. A prospective randomized trial of hyperfractionated versus conventional once daily radiation for advanced squamous cell carcinomas of the larynx and pharynx

    Cummings, B.J.; Keane, T.J.; Pintilie, M.; O'Sullivan, B.; Payne, D.; Warde, P.; McLean, M.; Waldron, J.; Liu, F.-F.; Gullane, P.

    1996-01-01

    Purpose: To examine the effects of an increased dose of radiation therapy (RT) delivered by a hyperfractionated schedule compared to conventional once daily RT on toxicity, locoregional control and survival in the treatment of squamous cell carcinomas (SCC) of the larynx and pharynx. Materials/Methods: Between 1988 and 1995 336 patients were randomized to receive RT with curative intent. Eligible patients had biopsy proven SCC of the larynx or pharynx, with TN stages (AJC-UICC 1987) T3 or T4 N0, or any T with any N+. All patients were M0. Patients were stratified by site (larynx/oropharynx/hypopharynx), node status (clinically positive/negative), and performance status. Patients were treated with either 51 Gy TAD/20 fractions/4 wk (2.55 Gy 1x/d, conventional RT=CRT) or 58 Gy TAD/40 fractions/4 wk (1.45 Gy 2x/d, hyperfractionated RT=HFRT). Patients underwent EUA and selective biopsies 10 wk after RT; surgical salvage was performed for residual or recurrent cancer whenever possible. Results: The primary cancer arose in the oropharynx (138), larynx (133) or hypopharynx (65). T stages were distributed T1 22, T2 72, T3 133 and T4 109. N stage distribution was N0 127, N1 74, N2 117 and N3 18. The proportion of patients with acute mucosal toxicity (RTOG Grade 3 or 4) was increased by HFRT (60% versus 40%), but other acute and late toxicity was not significantly different. There was no difference in the incidence of morbidity in the two treatment groups in those who underwent surgery following RT. The locoregional control rates at 3 yrs for all cases were 45% (HFRT) vs 40% (CRT) log rank p=0.16; for primary tumors <4 cm 54% (HFRT) vs 42% (CRT) p=0.04; for primary tumors ≥ 4 cm 38% (HFRT) vs 41% (CRT) p=0.73. Local control was improved to some extent in SCC which arose in all sites, but most noticeably in hypopharyngeal cancers. The disease free survival rates at 3 yr for all cases were 37% (HFRT) vs 30% (CRT) p=0.15; for primary tumors < 4 cm 47% (HFRT) vs 34% (CRT) p=0

  18. Comparative efficacy of tadalafil once daily in men with erectile dysfunction who demonstrated previous partial responses to as-needed sildenafil, tadalafil, or vardenafil.

    Kim, Edward; Seftel, Allen; Goldfischer, Evan; Baygani, Simin; Burns, Patrick

    2015-02-01

    Phosphodiesterase type-5 inhibitors (PDE5Is) are first-line therapies for erectile dysfunction (ED). Sildenafil (SIL) and vardenafil (VAR) are approved for as-needed (PRN) dosing; tadalafil (TAD) is approved for both PRN and once-a-day (OaD) dosing for ED. Recent evidence suggests that TAD-OaD may be effective as therapy in men with an incomplete response to PRN-PDE5I therapy. This study evaluated whether TAD-OaD provides similar efficacy in men with ED who had previously demonstrated a partial response to PRN-PDE5I therapy. In this randomized, double-blind, placebo-controlled trial, men with a ≥3 month ED history received SIL 100 mg, TAD 20 mg, or VAR 20 mg during a 4 week open-label lead-in period. Those with International Index of Erectile Function - Erectile Function (IIEF-EF) domain scores TAD 2.5 mg up-titrated to 5 mg, TAD 5 mg, or placebo (PBO) OaD for 12 weeks. MAIN OUTCOME MEASURES obtained from patients treated with TAD-OaD were compared to PBO-treated patients. Additionally, results of treatment with TAD-OaD were compared to results obtained from 4 week PRN-PDE5I therapy to determine whether OaD and PRN regimens provided comparable efficacy. NCT01130532. International Index of Erectile Function (IIEF) domain scores; Sexual Encounter Profile (SEP) questions 2-5. Endpoint data was obtained from 590 men (391 TAD; 199 PBO). RESULTS for all IIEF and SEP measures were significantly better for TAD-OaD (p TAD 2.5 mg and TAD 5 mg OaD therapy were safe and generally well tolerated. Tadalafil once daily is a viable alternative to as-needed PDE5I therapy in men with ED. Key limitations include the lack of a PRN PDE5I study group during the double-blind period, and that many more patients took tadalafil than sildenafil or vardenafil during the PRN period.

  19. Once-weekly albiglutide versus once-daily liraglutide in patients with type 2 diabetes inadequately controlled on oral drugs (HARMONY 7): a randomised, open-label, multicentre, non-inferiority phase 3 study

    Pratley, Richard E.; Nauck, Michael A.; Barnett, Anthony H.; Feinglos, Mark N.; Ovalle, Fernando; Harman-Boehm, Illana; Ye, June; Scott, Rhona; Johnson, Susan; Stewart, Murray; Rosenstock, Julio; Adamson, K.; Ahmann, A.; Ahn, C. W.; Ajani, D.; Akright, L.; Alwine, L.; Alzohaili, O.; Andrawis, N.; Arbañil Huaman, H.; Arora, S.; Bailey, T.; Barnett, A.; Baron, M.; Barreda Caceres, L.; Barrera, J.; Berg, J.; Bertenshaw, R.; Bode, B.; Bolton, D.; Brito, M.; Brock, S.; Brockmyre, A.; Broker, R.; Brusco, O.; Buynak, R.; Canadas-Zizzias, R.; Canas, G.; Capo, J.; Castillo Gamarra, M.; Cathcart, H.; Catindig, E. A.; Chilka, S.; Cho, Y. W.; Choi, D. S.; Chuck, L.; Cooper, M.; Corder, C.; Hoekstra, J.; Kemp, S.

    2014-01-01

    Background As new members of a drug class are developed, head-to-head trials are an important strategy to guide personalised treatment decisions. We assessed two glucagon-like peptide-1 receptor agonists, once-weekly albiglutide and once-daily liraglutide, in patients with type 2 diabetes

  20. Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycaemic agents (APOLLO): an open randomised controlled trial

    Bretzel, R.G.; Nuber, U.; Landgraf, W.

    2008-01-01

    BACKGROUND: As type 2 diabetes mellitus progresses, oral hypoglycaemic agents often fail to maintain blood glucose control and insulin is needed. We investigated whether the addition of once-daily insulin glargine is non-inferior to three-times daily prandial insulin lispro in overall glycaemic c...

  1. Effectiveness and gastrointestinal tolerability during conversion and titration with once-daily OROS® hydromorphone extended release in opioid-tolerant patients with chronic low back pain

    Hale ME

    2013-05-01

    Full Text Available Martin E Hale,1 Srinivas R Nalamachu,2 Arif Khan,3 Michael Kutch4,* 1Gold Coast Research, LLC, Weston, FL, USA; 2International Clinical Research Institute, Overland Park, KS, USA; 3MedNorthwest Clinical Research Center, Bellevue, WA, USA; Duke University Medical Center, Durham, NC, USA; 4Applied Clinical Intelligence, LLC, Bala Cynwyd, PA, USA *Affiliation at the time this work was completed. Michael Kutch is currently affiliated with Cytel Inc, Chesterbrook, PA, USA Purpose: To describe the efficacy and safety of hydromorphone extended-release tablets (OROS hydromorphone ER during dose conversion and titration. Patients and methods: A total of 459 opioid-tolerant adults with chronic moderate to severe low back pain participated in an open-label, 2- to 4-week conversion/titration phase of a double-blind, placebo-controlled, randomized withdrawal trial, conducted at 70 centers in the United States. Patients were converted to once-daily OROS hydromorphone ER at 75% of the equianalgesic dose of their prior total daily opioid dose (5:1 conversion ratio, and titrated as frequently as every 3 days to a maximum dose of 64 mg/day. The primary outcome measure was change in pain intensity numeric rating scale; additional assessments included the Patient Global Assessment and the Roland–Morris Disability Questionnaire scores. Safety assessments were performed at each visit and consisted of recording and monitoring all adverse events (AEs and serious AEs. Results: Mean (standard deviation final daily dose of OROS hydromorphone ER was 37.5 (17.8 mg. Mean (standard error of the mean [SEM] numeric rating scale scores decreased from 6.6 (0.1 at screening to 4.3 (0.1 at the final titration visit (mean [SEM] change, -2.3 [0.1], representing a 34.8% reduction. Mean (SEM change in Patient Global Assessment was -0.6 (0.1, and mean change (SEM in the Roland–Morris Disability Questionnaire was -2.8 (0.3. Patients achieving a stable dose showed greater improvement

  2. PGC-1beta is downregulated by training in human skeletal muscle: no effect of training twice every second day vs. once daily on expression of the PGC-1 family

    Mortensen, Ole Hartvig; Plomgaard, Peter; Fischer, Christian P

    2007-01-01

    We hypothesized that the peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) family of transcriptional coactivators (PGC-1alpha, PGC-1beta, and PRC) is differentially regulated by training once daily vs. training twice daily every second day and that this difference might...... be observed in the acute response to endurance exercise. Furthermore, we hypothesized that expression levels of the PGC-1 family differ with muscular fiber-type composition. Thus, before and after 10 wk of knee extensor endurance training, training one leg once daily and the other leg twice daily every second...... day, keeping the total amount of training for the legs equal, skeletal muscle mRNA expression levels of PGC-1alpha, PGC-1beta, and PRC were determined in young healthy men (n = 7) in response to 3 h of acute exercise. No significant difference was found between the two legs, suggesting that regulation...

  3. Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial.

    Rascol, O.; Brooks, D.J.; Melamed, E.; Oertel, W.; Poewe, W.; Stocchi, F.; Tolosa, E.; LARGO study group

    2005-01-01

    Lancet. 2005 Mar 12-18;365(9463):947-54. Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial. Rascol O, Brooks DJ, Melamed E, Oertel W, Poewe W, Stocchi F, Tolosa E; LARGO study group. Clinical Investigation Centre, Department of Clinical Pharmacology, University Hospital, Toulouse, France. ...

  4. Effects of Tadalafil Once-Daily or On-Demand vs Placebo on Return to Baseline Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy - Results from a Randomized Controlled Trial (REACTT)

    Mulhall, John P; Brock, Gerald; Oelke, Matthias

    2016-01-01

    INTRODUCTION AND AIM: The multicenter, randomized, double-blind, double-dummy, placebo-controlled REACTT trial suggested that treatment with tadalafil once daily (OaD) started early after bilateral nerve-sparing radical prostatectomy (nsRP) for prostate cancer may contribute to erectile function......: REACTT included 422 men blind treatment (DBT) with tadalafil 5 mg OaD (n = 139), tadalafil 20 mg on...

  5. Comparison of therapy augmentation and deviation rates from the recommended once-daily dosing regimen between LDX and commonly prescribed long-acting stimulants for the treatment of ADHD in youth and adults.

    Setyawan, Juliana; Hodgkins, Paul; Guérin, Annie; Gauthier, Geneviève; Cloutier, Martin; Wu, Eric; Erder, M Haim

    2013-10-01

    To compare therapy augmentation and deviation rates from the recommended once-daily dosing regimen in Attention Deficit Hyperactivity Disorder (ADHD) patients initiated on lisdexamfetamine (LDX) vs other once-daily Food and Drug Administration (FDA) approved stimulants. ADHD patients initiated on a long-acting ADHD stimulant medication (index medication) in/after 2007 were selected from a large U.S. administrative claims database. Patients were required to be persistent for ≥90 days and continuously enrolled in their healthcare plan for ≥12 months following treatment initiation date. Based on age and previous treatment status, patients were classified into treatment-naïve children and adolescents (6-17 years old), previously treated children and adolescents, treatment-naïve adults (≥18 years old), and previously treated adults. Furthermore, patients were classified into four mutually exclusive treatment groups, based on index medication: lisdexamfetamine (LDX), osmotic release methylphenidate hydrochloride long-acting (OROS MPH), other methylphenidate/dexmethylphenidate long-acting (MPH LA), and amphetamine/dextroamphetamine long-acting (AMPH LA). The average daily consumption was measured as the quantity of index medication supplied in the 12-month study period divided by the total number of days of supply. Therapy augmentation was defined as the use of another ADHD medication concomitantly with the index medication for ≥28 consecutive days. Therapy augmentation and deviation rates from the recommended once-daily dosing regimen were compared between treatment groups using multivariate logistic regression models. Compared to the other treatment groups, LDX patients were less likely to augment with another ADHD medication (range odds ratios [OR]; 1.28-3.30) and to deviate from the recommended once-daily dosing regimen (range OR; 1.73-4.55), except for previously treated adult patients, where therapy augmentation differences were not statistically

  6. Effect of prandial treatment timing adjustment, based on continuous glucose monitoring, in patients with type 2 diabetes uncontrolled with once-daily basal insulin: A randomized, phase IV study.

    Ilany, Jacob; Bhandari, Hamad; Nabriski, Dan; Toledano, Yoel; Konvalina, Noa; Cohen, Ohad

    2018-05-01

    To evaluate the glycaemic control achieved by prandial once-daily insulin glulisine injection timing adjustment, based on a continuous glucose monitoring sensor, in comparison to once-daily insulin glulisine injection before breakfast in patients with type 2 diabetes who are uncontrolled with once-daily basal insulin glargine. This was a 24-week open-label, randomized, controlled, multicentre trial. At the end of an 8-week period of basal insulin optimization, patients with HbA1c ≥ 7.5% and FPG sensor) or arm B (sensor) to receive 16-week intensified prandial glulisine treatment. Patients in arm A received pre-breakfast glulisine, and patients in arm B received glulisine before the meal with the highest glucose elevation based on sensor data. The primary outcome was mean HbA1c at week 24 and secondary outcomes included rates of hypoglycaemic events and insulin dosage. A total of 121 patients were randomized to arm A (n = 61) or arm B (n = 60). There was no difference in mean HbA1c at week 24 between arms A and B (8.5% ± 1.2% vs 8.4% ± 1.0%; P = .66). The prandial insulin glulisine dosage for arm A and arm B was 9.3 and 10.1 units, respectively (P = .39). The frequency of hypoglycaemic events did not differ between study arms (36.1% vs 51.7%; P = .08). Using a CGM sensor to identify the meal with the highest glucose excursion and adjusting the timing of prandial insulin treatment did not show any advantage in terms of glycaemic control or safety in our patients. © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  7. Liraglutide, a once-daily human GLP-1 analogue, improves pancreatic B-cell function and arginine-stimulated insulin secretion during hyperglycaemia in patients with Type 2 diabetes mellitus

    Vilsbøll, Tina; Brock, Birgitte; Perrild, Hans

    2008-01-01

    To assess the effect of liraglutide, a once-daily human glucagon-like peptide-1 analogue on pancreatic B-cell function. methods: Patients with Type 2 diabetes (n = 39) were randomized to treatment with 0.65, 1.25 or 1.9 mg/day liraglutide or placebo for 14 weeks. First- and second-phase insulin...... release were measured by means of the insulin-modified frequently sampled intravenous glucose tolerance test. Arginine-stimulated insulin secretion was measured during a hyperglycaemic clamp (20 mmol/l). Glucose effectiveness and insulin sensitivity were estimated by means of the insulin...

  8. Addition of topical pimecrolimus to once-daily mid-potent steroid confers no short-term therapeutic benefit in the treatment of severe atopic dermatitis; a randomized controlled trial.

    Spergel, J M; Boguniewicz, M; Paller, A S; Hebert, A A; Gallagher, P R; McCormick, C; Parneix-Spake, A; Hultsch, T

    2007-08-01

    Combination therapy with pimecrolimus cream 1%, a topical calcineurin inhibitor (TCI), and fluticasone propionate cream 0.05% (FP), a mid-potency topical corticosteroid, may have a synergistic effect for treatment of atopic dermatitis (AD) because their mechanism of action differs. To assess the efficacy of concomitant pimecrolimus twice daily/FP once daily vs. vehicle twice daily/FP once daily in patients with severe AD. An exploratory, 2-week, double-blind, randomized, within-patient study was conducted (n = 45). Two target areas of similar severity, size and location were assessed. Assessments included the modified Eczema Area and Severity Index (0-12 scale) (primary variable), localized investigator global assessment (0-4 scale) and Patients' Self-Assessment of Disease Severity (0-4 scale). Data for all variables were similar for the TCI/FP and vehicle/FP treatments. The efficacy observed for treatment of severe AD flares with this TCI/FP combination regimen was equivalent to that of vehicle/FP.

  9. Biomass Derived Chemicals: Furfural Oxidative Esterification to Methyl-2-furoate over Gold Catalysts

    Maela Manzoli

    2016-07-01

    Full Text Available The use of heterogeneous catalysis to upgrade biomass wastes coming from lignocellulose into higher value-added chemicals is one of the most explored subjects in the prospective vision of bio-refinery. In this frame, a lot of interest has been driven towards biomass-derived building block molecules, such as furfural. Gold supported catalysts have been successfully proven to be highly active and selective in the furfural oxidative esterification to methyl-2-furoate under mild conditions by employing oxygen as benign oxidant. Particular attention has been given to the studies in which the reaction occurs even without base as co-catalyst, which would lead to a more green and economically advantageous process. The Au catalysts are also stable and quite easily recovered and represent a feasible and promising route to efficiently convert furfural to methyl-2-furoate to be scaled up at industrial level.

  10. Efficacy and Safety of Sarecycline, a Novel, Once-Daily, Narrow Spectrum Antibiotic for the Treatment of Moderate to Severe Facial Acne Vulgaris: Results of a Phase 2, Dose-Ranging Study.

    Leyden, James J; Sniukiene, Vilma; Berk, David R; Kaoukhov, Alexandre

    2018-03-01

    There is a need for new oral antibiotics for acne with improved safety profiles and targeted antibacterial spectra. Sarecycline is a novel, tetracycline-class antibiotic specifically designed for acne, offering a narrow spectrum of activity compared with currently available tetracyclines, including less activity against enteric Gram-negative bacteria. This phase 2 study evaluated the efficacy and safety of three doses of sarecycline for moderate to severe facial acne vulgaris. In this multicenter, double-blind, placebo-controlled study, patients aged 12 to 45 years were randomized to once-daily sarecycline 0.75 mg/kg, 1.5 mg/kg, 3.0 mg/kg, or placebo. Efficacy analyses included change from baseline in inflammatory and noninflammatory lesion counts at week 12, with between-group comparisons using analysis of covariance. Safety assessments included adverse events (AEs), clinical laboratories, vital signs, electrocardiograms, and physical examinations. Overall, 285 randomized patients received at least one dose of study drug. At week 12, sarecycline 1.5 mg/kg and 3.0 mg/kg groups demonstrated significantly reduced inflammatory lesions from baseline (52.7% and 51.8%, respectively) versus placebo (38.3%; P=0.02 and P=0.03, respectively). Sarecycline was safe and well tolerated, with similar gastrointestinal AE rates in sarecycline and placebo groups. Vertigo and photosensitivity AEs occurred in less than 1% of patients when pooling sarecycline groups; no vulvovaginal candidiasis AEs occurred. Discontinuation rates due to AEs were low. No serious AEs occurred. Once-daily sarecycline 1.5 mg/kg significantly reduced inflammatory lesions versus placebo and was safe and well tolerated with low rates of AEs, including gastrointestinal AEs. Sarecycline 3.0 mg/kg did not result in additional efficacy versus 1.5 mg/kg. Sarecycline may represent a novel, once-daily treatment for patients with moderate to severe acne. It offers a narrow antibacterial spectrum relative to other

  11. Lung function efficacy and symptomatic benefit of olodaterol once daily delivered via Respimat® versus placebo and formoterol twice daily in patients with GOLD 2–4 COPD: results from two replicate 48-week studies

    Koch A

    2014-07-01

    Full Text Available Andrea Koch,1 Emilio Pizzichini,2 Alan Hamilton,3 Lorna Hart,3 Lawrence Korducki,4 Maria Cristina De Salvo,5 Pierluigi Paggiaro6 1Medical Clinic III for Pneumology, Allergology, Sleep and Respiratory Medicine, University Hospital Bochum-Bergmannsheil, Bochum, Germany; 2NUPAIVA (Asthma Research Center, Universidade Federal de Santa Catarina, Santa Catarina, Brazil; 3Boehringer Ingelheim, Burlington, Ontario, Canada; 4Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA; 5Centro Médico Dra. De Salvo, Fundación Respirar, Buenos Aires, Argentina; 6Cardio-Thoracic and Vascular Department, University of Pisa, Pisa, Italy Abstract: Two replicate, multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase III studies investigated the long-term efficacy and safety of once-daily olodaterol via Respimat® versus placebo and formoterol over 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease receiving usual-care background therapy. Patients received once-daily olodaterol 5 or 10 µg, twice-daily formoterol 12 µg, or placebo. Co-primary end points were forced expiratory volume in 1 second (FEV1 area under the curve from 0–3 hours response, FEV1 trough response, and Mahler transition dyspnea index total score after 24 weeks; secondary end points included St George's Respiratory Questionnaire. Overall, 904 (Study 1222.13 and 934 (Study 1222.14 patients received treatment. Olodaterol significantly improved FEV1 area under the curve from 0–3 hours versus placebo in both studies (with olodaterol 5 µg, 0.151 L and 0.129 L; with olodaterol 10 µg, 0.165 L and 0.154 L; for all comparisons P<0.0001 and FEV1 trough responses versus placebo (0.053–0.085 L; P<0.01, as did formoterol. Primary analysis revealed no significant difference in transition dyspnea index focal score for any active treatment versus placebo. Post hoc analysis using pattern mixture modeling (accounting for

  12. Onychomycosis of Toenails and Post-hoc Analyses with Efinaconazole 10% Solution Once-daily Treatment: Impact of Disease Severity and Other Concomitant Associated Factors on Selection of Therapy and Therapeutic Outcomes.

    Del Rosso, James Q

    2016-02-01

    Topical treatment for toenail onychomycosis has been fraught with a long-standing reputation of poor efficaey, primarily due to physical properties of the nail unit that impede drug penetration. Newer topical agents have been formulated as Solution, which appear to provide better therapeutic response in properly selected patients. It is important to recognize the impact the effects that mitigating and concomitant factors can have on efficaey. These factors include disease severity, gender, presence of tinea pedis, and diabetes. This article reviews results achieved in Phase 3 pivotal studies with topical efinaconazole 10% Solution applied once daily for 48 weeks with a focus on how the aforementioned factors influenced therapeutic outcomes. It is important for clinicians treating patients for onychomycosis to evaluate severity, treat concomitant tinea pedis, address control of diabetes if present by encouraging involvement of the patient's primary care physician, and consider longer treatment courses when clinically relevant.

  13. Inhalation by design: novel ultra-long-acting β(2)-adrenoreceptor agonists for inhaled once-daily treatment of asthma and chronic obstructive pulmonary disease that utilize a sulfonamide agonist headgroup.

    Glossop, Paul A; Lane, Charlotte A L; Price, David A; Bunnage, Mark E; Lewthwaite, Russell A; James, Kim; Brown, Alan D; Yeadon, Michael; Perros-Huguet, Christelle; Trevethick, Michael A; Clarke, Nicholas P; Webster, Robert; Jones, Rhys M; Burrows, Jane L; Feeder, Neil; Taylor, Stefan C J; Spence, Fiona J

    2010-09-23

    A novel series of potent and selective sulfonamide derived β(2)-adrenoreceptor agonists are described that exhibit potential as inhaled ultra-long-acting bronchodilators for the treatment of asthma and chronic obstructive pulmonary disease. Analogues from this series mediate very long-lasting smooth muscle relaxation in guinea pig tracheal strips. The sulfonamide agonist headgroup confers high levels of intrinsic crystallinity that could relate to the acidic sulfonamide motif supporting a zwitterionic form in the solid state. Optimization of pharmacokinetic properties was achieved through targeted introduction of a phenolic moiety to support rapid phase II clearance, thereby minimizing systemic exposure following inhalation and reducing systemically mediated adverse events. Compound 38 (PF-610355) is identified as a clinical candidate from this series, with in vivo duration of action studies confirming its potential for once-daily use in humans. Compound 38 is currently in advanced phase II clinical studies.

  14. Morning and evening behavior in children and adolescents treated with atomoxetine once daily for Attention-Deficit/Hyperactivity Disorder (ADHD: Findings from two 24-week, open-label studies

    Schacht Alexander

    2009-02-01

    Full Text Available Abstract Background The impact of once daily atomoxetine treatment on symptoms in children and adolescents with ADHD may vary over the day. In order to capture such variations, two studies were undertaken in children and adolescents with ADHD using two instruments that capture morning and evening behavior and ADHD-related difficulties over the day. This secondary measure analysis builds on two primary analyses that were conducted separately for children and adolescents and also published separately. Methods In two open-label studies, ADHD patients aged 6–17 years (n = 421, received atomoxetine in the morning (target-dose 0.5–1.2 mg/kg/day for up to 24 weeks. Morning and evening behavior was assessed using the investigator-rated Weekly Rating of Evening and Morning Behavior (WREMB-R scale. ADHD-related difficulties at various times of the day (morning, during school, during homework, evening were assessed using the Global Impression of Perceived Difficulties (GIPD scale, rated by patients, parents and physicians. Data from both studies were combined for this secondary measure analysis. Results Both WREMB-R subscores decreased significantly over time, the evening subscore from 13.7 (95% CI 13.2;14.2 at baseline to 8.0 (7.4;8.5 at week 2, the morning subscore from 4.3 (4.0;4.5 to 2.4 (2.2;2.6. Scores then remained stable until week 24. All GIPD items improved correspondingly. At all times of the day, patients rated ADHD-related difficulties as less severe than parents and physicians. Conclusion These findings from two open-label studies suggest that morning and evening behavior and ADHD-related difficulties in the mornings and evenings improve over time with once daily atomoxetine treatment.

  15. Fifteen-year results of a randomized prospective trial of hyperfractionated chest wall irradiation versus once-daily chest wall irradiation after chemotherapy and mastectomy for patients with locally advanced noninflammatory breast cancer

    Buchholz, Thomas A.; Strom, Eric A.; Oswald, Mary Jane; Perkins, George H.; Oh, Julia; Domain, Delora; Yu, Tse-Kuan; Woodward, Wendy A.; Tereffe, Welela; Singletary, S. Eva; Thomas, Eva; Buzdar, Aman U.; Hortobagyi, Gabriel N.; McNeese, Marsha D.

    2006-01-01

    Purpose: To analyze the results of a Phase III clinical trial that investigated whether a hyperfractionated radiotherapy (RT) schedule could reduce the risk of locoregional recurrence in patients with locally advanced breast cancer treated with chemotherapy and mastectomy. Methods and Materials: Between 1985 and 1989, 200 patients with clinical Stage III noninflammatory breast cancer were enrolled in a prospective study investigating neoadjuvant and adjuvant chemotherapy. Of the 179 patients treated with mastectomy after neoadjuvant chemotherapy, 108 participated in a randomized component of the trial that compared a dose-escalated, hyperfractionated (twice-daily, b.i.d.) chest wall RT schedule (72 Gy in 1.2-Gy b.i.d. fractions) with a once-daily (q.d.) schedule (60 Gy in 2-Gy q.d. fractions). In both arms of the study, the supraclavicular fossa and axillary apex were treated once daily to 50 Gy. The median follow-up period was 15 years. Results: The 15-year actuarial locoregional recurrence rate was 7% for the q.d. arm and 12% for the b.i.d. arm (p = 0.36). The rates of severe acute toxicity were similar (4% for q.d. vs. 5% for b.i.d.), but moist desquamation developed in 42% of patients in the b.i.d. arm compared with 28% of the patients in the q.d. arm (p = 0.16). The 15-year actuarial rate of severe late RT complications did not differ between the two arms (6% for q.d. vs. 11% for b.i.d., p = 0.54). Conclusion: Although the sample size of this study was small, we found no evidence that this hyperfractionation schedule of postmastectomy RT offered a clinical advantage. Therefore, we have concluded that it should not be further studied in this cohort of patients

  16. Mometasone-based triple combination therapy in melasma: Is it really safe?

    Majid Imran

    2010-01-01

    Full Text Available Background: Kligman′s triple combination formula has been one of the most popular treatment options in melasma over the last three decades. The original Kligman′s formula has been modified in many ways over the years and the most recent modification that has been introduced is a triple combination of 2% hydroquinone, 0.025% tretinoin, and 1% mometasone. The use of this triple combination in patients with melasma has seen a sharp rise over the last few years and with this rampant use the side-effect profile of this triple combination has also come to the fore. Aim : The aim of the present study was to assess the overall safety of the mometasone-based triple combination treatment in the management of melasma. Materials and Methods: This retrospective study was performed on 60 patients of melasma who had used a mometasone-based triple combination treatment for at least 3 weeks anytime in the previous 1 year. The patients were given a preformed questionnaire wherein they assessed the overall effect of the triple combination treatment on their melasma during its use as well as after its withdrawal. The patients were specifically asked about the status of their disease as well as the sun sensitivity of their skin before and after the use of triple combination treatment. In addition, the patients were assessed by a single trained dermatologist for the presence of any adverse effects arising out of the triple combination treatment in the form of telangiectasia, hypertrichosis, acne, skin atrophy, etc. Results: Majority of patients (51.7% had used the combination treatment well beyond the recommended duration. About one-third (36.7% of the patients rated their melasma as worse at the time of filling the questionnaire as compared with their disease before the use of triple combination treatment. On clinical examination, the evidence of steroid side effects was seen in 26 patients (43.3%. Steroid-induced telangiectasia was the commonest finding, seen

  17. Once-weekly albiglutide versus once-daily liraglutide in patients with type 2 diabetes inadequately controlled on oral drugs (HARMONY 7): a randomised, open-label, multicentre, non-inferiority phase 3 study.

    Pratley, Richard E; Nauck, Michael A; Barnett, Anthony H; Feinglos, Mark N; Ovalle, Fernando; Harman-Boehm, Illana; Ye, June; Scott, Rhona; Johnson, Susan; Stewart, Murray; Rosenstock, Julio

    2014-04-01

    As new members of a drug class are developed, head-to-head trials are an important strategy to guide personalised treatment decisions. We assessed two glucagon-like peptide-1 receptor agonists, once-weekly albiglutide and once-daily liraglutide, in patients with type 2 diabetes inadequately controlled on oral antidiabetic drugs. We undertook this 32-week, open-label, phase 3 non-inferiority study at 162 sites in eight countries: USA (121 sites), Australia (9 sites), Peru (7 sites), Philippines (7 sites), South Korea (5 sites), UK (5 sites), Israel (4 sites), and Spain (4 sites). 841 adult participants (aged ≥18 years) with inadequately controlled type 2 diabetes and a BMI between 20 and 45 kg/m(2) were enrolled and randomised in a 1:1 ratio to receive albiglutide 30 mg once weekly titrated to 50 mg at week 6, or liraglutide 0·6 mg once daily titrated to 1·2 mg at week 1 and 1·8 mg at week 2. The randomisation schedule was generated by an independent randomisation team by the permuted block method with a fixed block size of 16. Participants and investigators were unmasked to treatment. The primary endpoint was change from baseline in HbA1c for albiglutide versus liraglutide, with a 95% CI non-inferiority upper margin of 0·3%. The primary analysis was by modified intention to treat. The study is registered with ClinicalTrials.gov, number NCT01128894. 422 patients were randomly allocated to the albigultide group and 419 to the liraglutide group; 404 patients in the abliglutide group and 408 in the liraglutide group received the study drugs. The primary endpoint analysis was done on the modified intention-to-treat population, which included 402 participants in the albiglutide group and 403 in the liraglutide group. Model-adjusted change in HbA1c from baseline to week 32 was -0·78% (95% CI -0·87 to -0·69) in the albigludite group and -0·99% (-1·08 to -0·90) in the liraglutide group; treatment difference was 0·21% (0·08-0·34; non-inferiority p value=0

  18. The safety, tolerability, and efficacy of once-daily memantine (28 mg): a multinational, randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe Alzheimer's disease taking cholinesterase inhibitors.

    Grossberg, George T; Manes, Facundo; Allegri, Ricardo F; Gutiérrez-Robledo, Luis Miguel; Gloger, Sergio; Xie, Lei; Jia, X Daniel; Pejović, Vojislav; Miller, Michael L; Perhach, James L; Graham, Stephen M

    2013-06-01

    Immediate-release memantine (10 mg, twice daily) is approved in the USA for moderate-to-severe Alzheimer's disease (AD). This study evaluated the efficacy, safety, and tolerability of a higher-dose, once-daily, extended-release formulation in patients with moderate-to-severe AD concurrently taking cholinesterase inhibitors. In this 24-week, double-blind, multinational study (NCT00322153), outpatients with AD (Mini-Mental State Examination scores of 3-14) were randomized to receive once-daily, 28-mg, extended-release memantine or placebo. Co-primary efficacy parameters were the baseline-to-endpoint score change on the Severe Impairment Battery (SIB) and the endpoint score on the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus). The secondary efficacy parameter was the baseline-to-endpoint score change on the 19-item Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL19); additional parameters included the baseline-to-endpoint score changes on the Neuropsychiatric Inventory (NPI) and verbal fluency test. Data were analyzed using a two-way analysis of covariance model, except for CIBIC-Plus (Cochran-Mantel-Haenszel test). Safety and tolerability were assessed through adverse events and physical and laboratory examinations. A total of 677 patients were randomized to receive extended-release memantine (n = 342) or placebo (n = 335); completion rates were 79.8 and 81.2 %, respectively. At endpoint (week 24, last observation carried forward), memantine-treated patients significantly outperformed placebo-treated patients on the SIB (least squares mean difference [95 % CI] 2.6 [1.0, 4.2]; p = 0.001), CIBIC-Plus (p = 0.008), NPI (p = 0.005), and verbal fluency test (p = 0.004); the effect did not achieve significance on ADCS-ADL19 (p = 0.177). Adverse events with a frequency of ≥5.0 % that were more prevalent in the memantine group were headache (5.6 vs. 5.1 %) and diarrhea (5.0 vs. 3.9

  19. Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial.

    Rascol, O; Brooks, D J; Melamed, E; Oertel, W; Poewe, W; Stocchi, F; Tolosa, E

    Rasagiline mesylate is a novel drug for Parkinson's disease with selective, irreversible monoamine oxidase B (MAO-B) inhibitor activity, and is effective as monotherapy in early disease. This study investigated rasagiline efficacy and safety in levodopa-treated patients with Parkinson's disease and motor fluctuations. In an 18-week, double-blind, multicentre (74 hospitals and academic centres in Israel, Argentina, and Europe) trial, 687 outpatients were randomly assigned to oral rasagiline (231 individuals; 1 mg once daily), entacapone (227; 200 mg with every levodopa dose), or placebo (229). Primary outcome was change in total daily off-time (intention-to-treat population). Other measures included the clinical global improvement (CGI) score and unified Parkinson's disease rating scale (UPDRS) scores. Analysis was by intention to treat. 88 (13%) patients who were assigned treatment did not complete the study (23 rasagiline, 30 entacapone, 35 placebo), mainly because of withdrawal of consent (n=34) and adverse events (n=34). Both rasagiline and entacapone reduced mean daily off-time (-1.18 h rasagiline and -1.2 h entacapone vs placebo -0.4 h; p=0.0001, prasagiline and -0.72 entacapone vs -0.37 placebo; prasagiline reduces mean daily off-time and improves symptoms of Parkinson's disease in levodopa-treated patients with motor fluctuations, an effect similar to that of entacapone.

  20. Cost-effectiveness analysis of exenatide twice daily (BID) vs insulin glargine once daily (QD) as add-on therapy in Chinese patients with Type 2 diabetes mellitus inadequately controlled by oral therapies.

    Deng, Jing; Gu, Shuyan; Shao, Hui; Dong, Hengjin; Zou, Dajin; Shi, Lizheng

    2015-01-01

    To estimate cost-effectiveness of exenatide twice daily (BID) vs insulin glargine once daily (QD) as add-on therapy in Chinese type 2 diabetes patients not well controlled by oral anti-diabetic (OAD) agents. The Cardiff model was populated with data synthesized from three head-to-head randomized clinical trials of up to 30 weeks in China comparing exenatide BID vs insulin glargine as add-on therapies to oral therapies in the Chinese population. The Cardiff model generated outputs including macrovascular and microvascular complications, diabetes-specific mortality, costs, and quality-adjusted life years (QALYs). Cost and QALYs were estimated with a time horizon of 40 years at a discount rate of 3% from a societal perspective. Compared with insulin glargine plus OAD treatments, patients on exenatide BID plus OAD gained 1.88 QALYs, at an incremental cost saving of Chinese Renminbi (RMB) 114,593 (i.e., cost saving of RMB 61078/QALY). The cost-effectiveness results were robust to various sensitivity analyses including probabilistic sensitivity analysis. The variables with the most impact on incremental cost-effectiveness ratio included HbA1c level at baseline, health utilities decrement, and BMI at baseline. Compared with insulin glargine QD, exenatide BID as add-on therapy to OAD is a cost-effective treatment in Chinese patients inadequately controlled by OAD treatments.

  1. Optimization of health-care organization and perceived improvement of patient comfort by switching from intra-venous BU four-times-daily infusions to a once-daily administration scheme in adult hematopoietic stem cell recipients.

    Xhaard, A; Rzepecki, P; Valcarcel, D; Santarone, S; Fürst, S; Serrano, D; De Angelis, G; Krüger, W; Scheid, C

    2014-04-01

    Previous studies have shown an equivalent pharmacokinetic profile between four-times-daily (4QD) and once-daily (QD) administration of intra-venous (IV) BU, without increased toxicity. We assess the impact of a switch in IV BU from a 4QD to a QD schedule, in terms of health-care organization, staff working conditions, quality of care dispensed and perceived patient comfort. Clinicians, nurses and pharmacists from nine allogeneic transplantation units in five European countries were interviewed face to face. Overall perception of QD versus 4QD BU was very positive. Both administration schemes were evaluated to be equally efficaciousZ. QD BU was perceived to be safer and more convenient. Clinicians and nurses perceived that patient comfort was improved, due to fewer complications associated with repeated infusions, and avoiding night infusions associated with stress, anxiety and decreased quality of sleep. Switching from 4QD to QD BU had a significant impact on health-care organization, with a better integration in the overall management and usual timelines in the pharmacies and transplantation units. Time spent to prepare and administer BU was significantly reduced, leading to potential financial savings that merit further assessment and would be of particular interest in the current economic climate.

  2. Switch from a ZDV/3TC-based regimen to a completely once daily (QD regimen of emtricitabine/tenofovir DF fixed dose combination plus a third QD agent (SONETT

    Arasteh K

    2009-05-01

    Full Text Available Abstract Objectives To assess the efficacy and safety of a treatment switch from a twice-daily (BID regimen containing zidovudine (ZDV and lamivudine (3TC plus a third agent to a once daily (QD regimen containing the fixed-dose combination of tenofovir DF/emtricitabine (TDF/FTC, Truvada® plus a divergent third QD agent in HIV-1 infected patients. Methods Prospective, 48-week, non-randomised, single-group, open-label, study. Fifty-one patients on stable ZDV/3TC-containing HAART, with HIV-1 RNA 50 cells/μl, were switched to TDF/FTC plus a third agent. Plasma HIV-1 RNA, CD4+ and CD8+ T-cell counts were assessed at baseline and weeks 4, 12, 24, 36 and 48 post-switch. Results During the 48-week study, 10 patients discontinued prematurely, including three due to adverse events (AEs. At week 48, plasma HIV-1 RNA was p Conclusions Results from this study support switching from a ZDV/3TC-containing HAART regimen to a completely QD regimen of TDF/FTC plus a third agent. Virologic and immunologic control are maintained, with apparent benefits in haemoglobin.

  3. Dapagliflozin once-daily and exenatide once-weekly dual therapy: A 24-week randomized, placebo-controlled, phase II study examining effects on body weight and prediabetes in obese adults without diabetes.

    Lundkvist, Per; Sjöström, C David; Amini, Sam; Pereira, Maria J; Johnsson, Eva; Eriksson, Jan W

    2017-01-01

    To explore the effects of dual therapy with dapagliflozin and exenatide on body weight, body composition, glycaemic variables and systolic blood pressure (SBP) in obese adults without diabetes. In this single-centre, double-blind trial, we randomized 50 obese adults without diabetes (aged 18-70 years; body mass index 30-45 kg/m 2 ) to oral dapagliflozin 10 mg once daily plus subcutaneous long-acting exenatide 2 mg once weekly or placebo. MRI was used to assess change in body composition. Participants were instructed to follow a balanced diet and exercise moderately. Of 25 dapagliflozin/exenatide- and 25 placebo-treated participants, 23 (92.0%) and 20 (80.0%) completed 24 weeks of treatment, respectively. At baseline, the mean participant age was 52 years, 61% were female, the mean body weight was 104.6 kg, and 73.5% of participants had prediabetes (impaired fasting glucose or impaired glucose tolerance). After 24 weeks, for dapagliflozin/exenatide versus placebo: the difference in body weight change was -4.13 kg (95% confidence interval -6.44, -1.81; P prediabetes was less frequent with active treatment (34.8% vs 85.0%, respectively; P prediabetes and SBP over 24 weeks and was well tolerated in obese adults without diabetes. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  4. Safety and Effectiveness of Once-Daily Tadalafil (5 mg Therapy in Korean Men with Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms in a Real-World Clinical Setting: Results from a Post- Marketing Surveillance Study

    Ji Eon Won

    2018-05-01

    Full Text Available Purpose: The aim of this study was to investigate the safety and effectiveness of tadalafil 5 mg once daily (quaque die [everyday], QD among Korean men with benign prostatic hyperplasia (BPH/lower urinary tract symptoms (LUTS in a real-world clinical setting. Materials and Methods: This was a single-country, prospective, observational cohort study in which patients newly prescribed tadalafil 5 mg QD for the treatment of BPH/LUTS were followed-up for 12±2 or 24±2 weeks, or to the last treatment, during post-marketing surveillance. Safety was evaluated in terms of the frequency of treatment-emergent adverse events (TEAEs and serious adverse events (SAEs. Effectiveness was assessed by changes in the International Prostate Symptom Score (IPSS from baseline to each endpoint. Results: All patients receiving ≥1 dose of tadalafil 5 mg QD (N=637 were included in the safety population. Two percent of patients (n=13 experienced 15 TEAEs of mild (n=10; 66.7% or moderate (n=5; 33.3% severity. No severe TEAEs and no SAEs were reported. Effectiveness evaluations included all patients receiving tadalafil who had both baseline and endpoint observations (12-week, N=265; 24-week, N=44. Compared with baseline, the mean IPSS total score (±standard error significantly improved by 4.7±0.3 and 6.4±0.7 points at the 12- and 24-week endpoints, respectively (p<0.0001, with significant improvements also observed on the storage, voiding, and quality of life subscores. In total, 69.1% of the patients had a clinically meaningful ≥3-point improvement in the IPSS total score. Conclusions: Tadalafil 5 mg QD was well tolerated and effective in Korean men with BPH/LUTS in a real-world clinical setting.

  5. Safety and Effectiveness of Once-Daily Tadalafil (5 mg) Therapy in Korean Men with Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms in a Real-World Clinical Setting: Results from a Post-Marketing Surveillance Study.

    Won, Ji Eon; Chu, Ji Yeon; Choi, Hyunah Caroline; Chen, Yun; Park, Hyun Jun; Dueñas, Héctor José

    2018-05-01

    The aim of this study was to investigate the safety and effectiveness of tadalafil 5 mg once daily (quaque die [everyday], QD) among Korean men with benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) in a real-world clinical setting. This was a single-country, prospective, observational cohort study in which patients newly prescribed tadalafil 5 mg QD for the treatment of BPH/LUTS were followed-up for 12±2 or 24±2 weeks, or to the last treatment, during post-marketing surveillance. Safety was evaluated in terms of the frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Effectiveness was assessed by changes in the International Prostate Symptom Score (IPSS) from baseline to each endpoint. All patients receiving ≥1 dose of tadalafil 5 mg QD (N=637) were included in the safety population. Two percent of patients (n=13) experienced 15 TEAEs of mild (n=10; 66.7%) or moderate (n=5; 33.3%) severity. No severe TEAEs and no SAEs were reported. Effectiveness evaluations included all patients receiving tadalafil who had both baseline and endpoint observations (12-week, N=265; 24-week, N=44). Compared with baseline, the mean IPSS total score (±standard error) significantly improved by 4.7±0.3 and 6.4±0.7 points at the 12- and 24-week endpoints, respectively (peffective in Korean men with BPH/LUTS in a real-world clinical setting. Copyright © 2018 Korean Society for Sexual Medicine and Andrology.

  6. Cost-effectiveness of once daily GLP-1 receptor agonist lixisenatide compared to bolus insulin both in combination with basal insulin for the treatment of patients with type 2 diabetes in Norway.

    Huetson, Pernilla; Palmer, James L; Levorsen, Andrée; Fournier, Marie; Germe, Maeva; McLeod, Euan

    2015-01-01

    Lixisenatide is a potent, selective and short-acting once daily prandial glucagon-like peptide-1 receptor agonist which lowers glycohemoglobin and body weight by clinically significant amounts in patients with type 2 diabetes treated with basal insulin, with limited risk of hypoglycemia. To assess the cost-effectiveness of lixisenatide versus bolus insulin, both in combination with basal insulin, in patients with type 2 diabetes in Norway. The IMS CORE Diabetes Model, a non-product-specific and validated simulation model, was used to make clinical and cost projections. Transition probabilities, risk adjustments and the progression of complication risk factors were derived from the UK Prospective Diabetes Study, supplemented with Norwegian data. Patients were assumed to receive combination treatment with basal insulin, lixisenatide or bolus insulin therapy for 3 years, followed by intensification of a basal-bolus insulin regimen for their remaining lifetime. Simulated healthcare costs, taken from the public payer perspective, were derived from microcosting and diagnosis related groups, discounted at 4% per annum and reported in Norwegian krone (NOK). Productivity costs were also captured based on extractions from the Norwegian Labor and Welfare Administration. Health state utilities were derived from a systematic literature review. Sensitivity and scenario analyses were performed. Lixisenatide in combination with basal insulin was associated with increased quality-adjusted life years (QALYs) and reduced lifetime healthcare costs compared to bolus insulin in combination with basal insulin in patients with Type 2 diabetes, and can be considered dominant. The net monetary benefit of lixisenatide versus bolus insulin was NOK 39,369 per patient. Results were sensitive to discounting, the application of excess body weight associated disutility and uncertainty surrounding the changes in HbA1c. Lixisenatide may be considered an economically efficient therapy in combination

  7. Comparison of insulin intensification strategies with insulin lispro low mixture twice daily versus basal insulin glargine and prandial insulin lispro once daily in East Asian and Caucasian patients with type 2 diabetes mellitus.

    Jeong, In-Kyung; Chung, Choon Hee; Zhou, Zhiguang; Han, Jeong Hee; Duan, Ran; Edralin, Diana M; Rodriguez, Angel

    2017-04-01

    This analysis evaluated efficacy and safety of insulin lispro low mixture (LM25) twice daily (breakfast and dinner) versus basal insulin glargine (bedtime) plus prandial insulin lispro (IGL) once daily before the largest meal in East Asian (EA) and Caucasian patients with type 2 diabetes mellitus who failed to reach glycemic targets on basal insulin glargine with metformin and/or pioglitazone. Included patients had an HbA1c ≥7.5% and ≤10.5% and fasting plasma glucose ≤6.7 mmol/L. Primary outcome was HbA1c change at 24 weeks. Baseline mean HbA1c was numerically similar between groups in EA (n = 79) and Caucasian (n = 278) patients. Mean (± SD) HbA1c decreased significantly from baseline to 24 weeks for LM25 and IGL in both subpopulations (EA: -1.32 ± 0.96% and -0.89 ± 0.96%; Caucasian: -1.24 ± 0.98% and -1.04 ± 0.97; all P 1). The respective proportions reaching HbA1c ≤7.0% at Week 24 in the LM25 and IGL groups were 33.3% and 22.9% (EA) and 37.2% and 34.1% (Caucasian). Mean (± SD) rates of hypoglycemia per 30 days in the LM25 and IGL groups were 0.74 ± 1.16 and 1.22 ± 1.36 (EA) and 1.38 ± 2.04 and 1.65 ± 2.43 (Caucasian). Mean (± SD) weight gain changes in the LM25 and IGL groups were 0.62 ± 2.78 and 0.51 ± 2.63 kg (EA) and 1.77 ± 2.91 and 0.67 ± 3.09 kg (Caucasian). Both strategies improved glycemic control in a small group of EA and Caucasian patients not adequately controlled on insulin glargine plus metformin and/or pioglitazone. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  8. The short-term cost-effectiveness of once-daily liraglutide versus once-weekly exenatide for the treatment of type 2 diabetes mellitus in the United States.

    Bruce Wang

    Full Text Available Type 2 diabetes mellitus (T2DM is a chronic metabolic disease with substantial morbidity, mortality, and economic impacts. Glucagon-like peptide-1 (GLP-1 receptor agonists, such as once-daily (QD liraglutide and once-weekly (QW exenatide, are FDA-approved treatment for T2DM. Head-to-head trials and meta-analyses comparing these agents have reported clinically meaningful improvements but small differences in glycemic control between both agents. In this study, we calculate and compare the cost-effectiveness implications of these alternative effectiveness outcomes.We developed a decision model to evaluate the short-term cost-effectiveness of exenatide QW 2 mg versus liraglutide QD 1.8 mg in T2DM patients, with effectiveness measured as reduction in glycated hemoglobin (HbA1c. In the base case, the model tracks change in HbA1c and direct medical expenditure over a 6-month time horizon. We calculated and compared the cost per 1% reduction in HbA1c of models populated with clinical data from a head-to-head randomized, controlled trial (DURATION-6 and a network meta-analysis. Expenditure inputs were derived from wholesale acquisition costs and published sources.In the base case, 6-month expenditure for the liraglutide and exenatide strategies were $3,509 and $2,618, respectively. Using clinical data from DURATION-6 and the network meta-analysis, the liraglutide strategy had an incremental cost per 1% reduction in HbA1c of $4,773 and $27,179, respectively. The most influential model parameters were drug costs, magnitude of HbA1c reduction in patients on treatment for >1 month, and liraglutide gastrointestinal adverse event rate. In probabilistic sensitivity analyses (PSA using DURATION-6 data, the exenatide strategy was optimal at willingness-to-pay levels below $4,800 per 1% reduction in HbA1c. In a PSA using meta-analysis data, the exenatide strategy was dominant.Our modeled results demonstrate that the effectiveness and cost-effectiveness of

  9. Randomised study to assess the efficacy and safety of once-daily etravirine-based regimen as a switching strategy in HIV-infected patients receiving a protease inhibitor-containing regimen. Etraswitch study.

    Patricia Echeverría

    Full Text Available Etravirine (ETR was approved for patients with virological failure and antiretroviral resistance mutations. It has also shown antiviral efficacy in antiretroviral-naïve patients. However, data on the switching from protease inhibitors (PI to ETR are lacking.HIV-1-infected patients with suppressed viral load (VL during a PI-containing regimen (>12 months and no previous virological failure were randomized to switch from the PI to ETR (400 mg/day, dissolved in water (ETR group, n = 22 or to continue with the same regimen (control group, n = 21. Percentage of patients with VL ≤ 50 copies/mL were assessed at week 48, as well as changes in CD4 T-cell counts and metabolic profile.We included 43 patients [72.9% male, 46.3 (42.2; 50.6 years]. Two patients receiving ETR (grade-1 diarrhea and voluntary discontinuation and another in the control group (simplification discontinued therapy early. No patients presented virological failure (two consecutive VL>50 copies/mL; treatment was successful in 95.2% of the control group and 90.9% of the ETR group (intention-to-treat analysis, missing = failure (p = 0.58. CD4+ T-cell counts did not significantly vary [+49 cells/µL in the ETR group (p = 0.25 and -4 cells/µL in the control group (p = 0.71]. The ETR group showed significant reductions in cholesterol (p<0.001, triglycerides (p = <0.001, and glycemia (p = 0.03 and higher satisfaction (0-10 scale (p = 0.04. Trough plasma concentrations of ETR were similar to observed in studies using ETR twice daily.Switch from a PI-based regimen to a once-daily combination based on ETR maintained undetectable VL during 48 weeks in virologically suppressed HIV-infected patients while lipid profile and patient satisfaction improved significantly.ClinicalTrials.gov NCT01034917.

  10. Pharmacodynamic analysis and clinical trial of amoxicillin sprinkle administered once daily for 7 days compared to penicillin V potassium administered four times daily for 10 days in the treatment of tonsillopharyngitis due to Streptococcus pyogenes in children.

    Pichichero, M E; Casey, J R; Block, S L; Guttendorf, R; Flanner, H; Markowitz, D; Clausen, S

    2008-07-01

    An a priori pharmacokinetic/pharmacodynamic (PK/PD) target of 40% daily time above the MIC (T >MIC; based on the MIC(90) of 0.06 microg/ml for Streptococcus pyogenes reported in the literature) was shown to be achievable in a phase 1 study of 23 children with a once-daily (QD) modified-release, multiparticulate formulation of amoxicillin (amoxicillin sprinkle). The daily T >MIC achieved with the QD amoxicillin sprinkle formulation was comparable to that achieved with a four-times-daily (QID) penicillin VK suspension. An investigator-blinded, randomized, parallel-group, multicenter study involving 579 children 6 months to 12 years old with acute streptococcal tonsillopharyngitis was then undertaken. Children were randomly assigned 1:1 to receive either the amoxicillin sprinkle (475 mg for ages 6 months to 4 years, 775 mg for ages 5 to 12 years) QD for 7 days or 10 mg/kg of body weight of penicillin VK QID for 10 days (up to the maximum dose of 250 mg QID). Unexpectedly, the rates of bacteriological eradication at the test of cure were 65.3% (132/202) for the amoxicillin sprinkle and 68.0% (132/194) for penicillin VK (95% confidence interval, -12.0% to 6.6%). Thus, neither antibiotic regimen met the minimum criterion of > or =85% eradication ordinarily required by the U.S. FDA for first-line treatment of tonsillopharyngitis due to S. pyogenes. The results of subgroup analyses across demographic characteristics and current infection characteristics and by age/weight categories were consistent with the primary-efficacy result. The clinical cure rates for amoxicillin sprinkle and penicillin VK were 86.1% (216/251) and 91.9% (204/222), respectively (95% confidence interval, -11.6% to -0.4%). The results of a post hoc PD analysis suggested that a requirement for 60% daily T >MIC(90) more accurately predicted the observed high failure rates for bacteriologic eradication with the amoxicillin sprinkle and penicillin VK suspension studied. Based on the association between

  11. Pharmacodynamic Analysis and Clinical Trial of Amoxicillin Sprinkle Administered Once Daily for 7 Days Compared to Penicillin V Potassium Administered Four Times Daily for 10 Days in the Treatment of Tonsillopharyngitis Due to Streptococcus pyogenes in Children▿

    Pichichero, M. E.; Casey, J. R.; Block, S. L.; Guttendorf, R.; Flanner, H.; Markowitz, D.; Clausen, S.

    2008-01-01

    An a priori pharmacokinetic/pharmacodynamic (PK/PD) target of 40% daily time above the MIC (T >MIC; based on the MIC90 of 0.06 μg/ml for Streptococcus pyogenes reported in the literature) was shown to be achievable in a phase 1 study of 23 children with a once-daily (QD) modified-release, multiparticulate formulation of amoxicillin (amoxicillin sprinkle). The daily T >MIC achieved with the QD amoxicillin sprinkle formulation was comparable to that achieved with a four-times-daily (QID) penicillin VK suspension. An investigator-blinded, randomized, parallel-group, multicenter study involving 579 children 6 months to 12 years old with acute streptococcal tonsillopharyngitis was then undertaken. Children were randomly assigned 1:1 to receive either the amoxicillin sprinkle (475 mg for ages 6 months to 4 years, 775 mg for ages 5 to 12 years) QD for 7 days or 10 mg/kg of body weight of penicillin VK QID for 10 days (up to the maximum dose of 250 mg QID). Unexpectedly, the rates of bacteriological eradication at the test of cure were 65.3% (132/202) for the amoxicillin sprinkle and 68.0% (132/194) for penicillin VK (95% confidence interval, −12.0% to 6.6%). Thus, neither antibiotic regimen met the minimum criterion of ≥85% eradication ordinarily required by the U.S. FDA for first-line treatment of tonsillopharyngitis due to S. pyogenes. The results of subgroup analyses across demographic characteristics and current infection characteristics and by age/weight categories were consistent with the primary-efficacy result. The clinical cure rates for amoxicillin sprinkle and penicillin VK were 86.1% (216/251) and 91.9% (204/222), respectively (95% confidence interval, −11.6% to −0.4%). The results of a post hoc PD analysis suggested that a requirement for 60% daily T >MIC90 more accurately predicted the observed high failure rates for bacteriologic eradication with the amoxicillin sprinkle and penicillin VK suspension studied. Based on the association between longer

  12. Long-term safety and effectiveness of once-daily, single-entity, extended-release hydrocodone over 76 weeks of an open-label study in patients with chronic noncancer and nonneuropathic pain.

    Taber, Louise; Lynch, Shau Yu; He, Ellie; Ripa, Steven R

    2016-01-01

    To evaluate long-term use of Hysingla(®) ER (HYD), a single-entity, extended-release, once-daily hydrocodone bitartrate tablet with abuse-deterrent properties in patients with moderate-to-severe chronic noncancer and nonneuropathic pain. This open-label study consisted of a dose-titration period (up to 45 days), a 52-week maintenance period and a 24-week extension period. Opioid-naïve or opioid-experienced patients with controlled or uncontrolled chronic pain conditions were treated with HYD 20-120 mg daily. Supplemental nonopioid and short-acting opioid analgesics were permitted. This paper presents the results of 106 patients who continued HYD treatment for up to 76 weeks. Primary safety measures included the incidence of adverse events, as well as audiologic, clinical laboratory and electrocardiogram measurements. Effectiveness was measured by the change between baseline and the overall 76-week treatment period in "average pain over the last 24 h" (0 = no pain, 10 = pain as bad as you can imagine), Brief Pain Inventory-Short Form survey, Medical Outcomes Study 36-Item Short Form Health Survey, Medical Outcomes Study Sleep Scale-Revised and concomitant nonstudy opioid analgesic use. Among 410 patients who completed the maintenance period, 106 continued into the extension. Of these, 83 (78%) completed the entire 76-week treatment period. Treatment-emergent adverse events were typical of those observed with μ-opioid agonists. No study drug abuse or diversion was reported. Clinically important analgesia and functional improvement were achieved during the dose-titration period and were maintained in most patients throughout 76 weeks without the need for continued HYD dose increases or changes in concomitant nonstudy opioid analgesics. The mean pain score was 6.1 at baseline, 3.8 at the end of the dose titration period and 3.8 through 76 weeks. HYD was generally well tolerated. No unexpected safety concerns emerged. Pain control was sustained throughout 76 weeks of

  13. Pneumonia risk with inhaled fluticasone furoate and vilanterol compared with vilanterol alone in patients with COPD

    Crim, Courtney; Dransfield, Mark T; Bourbeau, Jean

    2015-01-01

    : Radiographically confirmed pneumonia risk is increased with inhaled FF/VI, although at less than investigator-defined rates. Modifiable pneumonia risk factors should be considered when attempting to optimize COPD management. Clinical trial registered with www.clinicaltrials.gov (NCT01009463 [HZC102871]; NCT......RATIONALE: Radiographically confirmed pneumonia risk with inhaled corticosteroid use in chronic obstructive pulmonary disease (COPD) has not been assessed to date. OBJECTIVES: To determine the incidence of pneumonia, risk factors, and clinical attributes with inhaled fluticasone furoate (FF...... with compatible parenchymal infiltrates, the respective incidences were 2, 4, 4, and 5%. Factors associated with at least a twofold increase in the risk of pneumonia with FF/VI treatment were being a current smoker, having prior pneumonia, body mass index

  14. Comparison of Mometasone Furoate Monohydrate (Nasonex and Fluticasone Propionate (Flixonase Nasal Sprays in the Treatment of Dust Mite-sensitive Children with Perennial Allergic Rhinitis

    Ka-Kit Mak

    2013-08-01

    Conclusion: Following the 4-week therapy, MFM provided greater improvement compared to FP for symptoms of childhood perennial-allergic rhinitis. Based on their TSSs, the MFM group experienced more effective relief of nasal symptoms, whereas the FP group experienced more effective relief of non-nasal symptoms.

  15. Effect of illicit direct to consumer advertising on use of etanercept, mometasone, and tegaserod in Canada: controlled longitudinal study

    Majumdar, Sumit R; Soumerai, Stephen B

    2008-01-01

    Objective To assess the impact of direct to consumer advertising of prescription drugs in the United States on Canadian prescribing rates for three heavily marketed drugs—etanercept, mometasone, and tegaserod. Design Controlled quasi-experimental study using interrupted time series analysis. Population Representative sample of 2700 Canadian pharmacies and prescription data from 50 US Medicaid programmes. Main outcome measures Differences in number of filled prescriptions per 10 000 population per month between English speaking and French speaking (control) Canadian provinces before and after the start of direct to consumer advertising in the United States. Results Spending on direct to consumer advertising for study drugs ranged from $194m to $314m (£104m-£169m; €131m-€212m) over the study period. Prescription rates for etanercept and mometasone did not increase in English speaking provinces relative to French speaking controls after the start of direct to consumer advertising. In contrast, tegaserod prescriptions increased 42% (0.56 prescriptions/10 000 residents, 95% confidence interval 0.37 to 0.76) in English speaking provinces immediately after the start of US direct to consumer advertising. Uncontrolled analysis of US Medicaid data showed a larger 56% increase in tegaserod prescriptions. However, this increase did not persist over time in either country, despite continued advertising. Conclusions Exposure to US direct to consumer advertising transiently influenced both Canadian and US prescribing rates for tegaserod, a drug later withdrawn owing to safety concerns. The impact of direct to consumer advertising on drug use seems to be highly variable and probably depends on the characteristics of the advertised drug, the level of exposure to direct to consumer advertising, and the cultural context. PMID:18765444

  16. Effect of illicit direct to consumer advertising on use of etanercept, mometasone, and tegaserod in Canada: controlled longitudinal study.

    Law, Michael R; Majumdar, Sumit R; Soumerai, Stephen B

    2008-09-02

    To assess the impact of direct to consumer advertising of prescription drugs in the United States on Canadian prescribing rates for three heavily marketed drugs-etanercept, mometasone, and tegaserod. Controlled quasi-experimental study using interrupted time series analysis. Representative sample of 2700 Canadian pharmacies and prescription data from 50 US Medicaid programmes. Differences in number of filled prescriptions per 10,000 population per month between English speaking and French speaking (control) Canadian provinces before and after the start of direct to consumer advertising in the United States. Spending on direct to consumer advertising for study drugs ranged from $194m to $314m ( pound104m- pound169m; euro131m-euro212m) over the study period. Prescription rates for etanercept and mometasone did not increase in English speaking provinces relative to French speaking controls after the start of direct to consumer advertising. In contrast, tegaserod prescriptions increased 42% (0.56 prescriptions/10,000 residents, 95% confidence interval 0.37 to 0.76) in English speaking provinces immediately after the start of US direct to consumer advertising. Uncontrolled analysis of US Medicaid data showed a larger 56% increase in tegaserod prescriptions. However, this increase did not persist over time in either country, despite continued advertising. Exposure to US direct to consumer advertising transiently influenced both Canadian and US prescribing rates for tegaserod, a drug later withdrawn owing to safety concerns. The impact of direct to consumer advertising on drug use seems to be highly variable and probably depends on the characteristics of the advertised drug, the level of exposure to direct to consumer advertising, and the cultural context.

  17. A double-blind, placebo-controlled, randomised, parallel-group, dose-escalating, repeat dose study in healthy volunteers to evaluate the safety, tolerability, pharmacodynamic effects and pharmacokinetics of the once daily rectal application of NRL001 suppositories for 14 days.

    Bell, D; Duffin, A; Jacobs, A; Pediconi, C; Gruss, H J

    2014-03-01

    The 1R,2S stereoisomer of methoxamine hydrochloride, NRL001, is a highly selective α1-adrenoceptor agonist being developed for the local treatment of non-structural faecal incontinence caused by weak internal anal sphincter tone. This study investigated the steady state pharmacokinetics (PK) and safety of 2 g rectal suppositories containing NRL001 in different strengths (7.5, 10, 12.5 or 15 mg). Healthy volunteers aged 18-45 years received 14 daily doses of NRL001 2 g suppositories or matching placebo. In each dose group nine participants received NRL001 and three received placebo. Blood samples to determine NRL001 concentrations were taken on Days 1, 7 and 14. Cardiovascular parameters were collected via electrocardiograms, Holter monitoring (three lead Holter monitor) and vital signs. Forty-eight volunteers were enrolled; 43 completed the study and were included in the PK analysis population. AUC and Cmax broadly increased with increasing dose, Tmax generally occurred between 4.0 and 5.0 h. Although the data did not appear strongly dose proportional, dose proportionality analysis did not provide evidence against dose proportionality as the log(dose) coefficients were not significantly < 1. NRL001 did not accumulate over time for any dose. Increasing NRL001 concentrations were related to changes in vital sign variables, most notably decreased heart rate. The most commonly reported adverse events (AEs) in the active treatment groups were paraesthesia and piloerection. Treatment with NRL001 was generally well tolerated over 14 days once daily dosing and plasma NRL001 did not accumulate over time. Treatment was associated with changes in vital sign variables, most notably decreased heart rate. AEs commonly reported with NRL001 treatment were events indicative of a systemic α-adrenergic effect. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  18. Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1): an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study to investigate the effect of once daily nitisinone on 24-h urinary homogentisic acid excretion in patients with alkaptonuria after 4 weeks of treatment.

    Ranganath, Lakshminarayan R; Milan, Anna M; Hughes, Andrew T; Dutton, John J; Fitzgerald, Richard; Briggs, Michael C; Bygott, Helen; Psarelli, Eftychia E; Cox, Trevor F; Gallagher, James A; Jarvis, Jonathan C; van Kan, Christa; Hall, Anthony K; Laan, Dinny; Olsson, Birgitta; Szamosi, Johan; Rudebeck, Mattias; Kullenberg, Torbjörn; Cronlund, Arvid; Svensson, Lennart; Junestrand, Carin; Ayoob, Hana; Timmis, Oliver G; Sireau, Nicolas; Le Quan Sang, Kim-Hanh; Genovese, Federica; Braconi, Daniela; Santucci, Annalisa; Nemethova, Martina; Zatkova, Andrea; McCaffrey, Judith; Christensen, Peter; Ross, Gordon; Imrich, Richard; Rovensky, Jozef

    2016-02-01

    Alkaptonuria (AKU) is a serious genetic disease characterised by premature spondyloarthropathy. Homogentisate-lowering therapy is being investigated for AKU. Nitisinone decreases homogentisic acid (HGA) in AKU but the dose-response relationship has not been previously studied. Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1) was an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study. The primary objective was to investigate the effect of different doses of nitisinone once daily on 24-h urinary HGA excretion (u-HGA24) in patients with AKU after 4 weeks of treatment. Forty patients were randomised into five groups of eight patients each, with groups receiving no treatment or 1 mg, 2 mg, 4 mg and 8 mg of nitisinone. A clear dose-response relationship was observed between nitisinone and the urinary excretion of HGA. At 4 weeks, the adjusted geometric mean u-HGA24 was 31.53 mmol, 3.26 mmol, 1.44 mmol, 0.57 mmol and 0.15 mmol for the no treatment or 1 mg, 2 mg, 4 mg and 8 mg doses, respectively. For the most efficacious dose, 8 mg daily, this corresponds to a mean reduction of u-HGA24 of 98.8% compared with baseline. An increase in tyrosine levels was seen at all doses but the dose-response relationship was less clear than the effect on HGA. Despite tyrosinaemia, there were no safety concerns and no serious adverse events were reported over the 4 weeks of nitisinone therapy. In this study in patients with AKU, nitisinone therapy decreased urinary HGA excretion to low levels in a dose-dependent manner and was well tolerated within the studied dose range. EudraCT number: 2012-005340-24. Registered at ClinicalTrials.gov: NCTO1828463. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  19. Long-term maintenance therapy for vulvar lichen sclerosus: the results of a randomized study comparing topical vitamin E with an emollient.

    Virgili, Annarosa; Minghetti, Sara; Borghi, Alessandro; Corazza, Monica

    2013-04-01

    The chronic and relapsing nature of vulvar lichen sclerosus (VLS) represents a challenge for its long-term management after an effective treatment with topical corticosteroids. To compare the effect of topical vitamin E with that of an emollient in reducing the risk of VLS relapse over a 52-week maintenance treatment. 156 patients with VLS were enrolled in a 12-week active treatment phase on topical 0.1% mometasone furoate ointment once daily. Those who achieved disease remission entered a 52-week maintenance phase in which patients were randomized to apply either an emollient or topical vitamin E once daily. 80 patients entered the maintenance phase. At 52 weeks, for the vitamin E maintenance group, the cumulative crude relapse rate was 27.8% and the cumulative modified crude relapse rate was 55.6%. For the emollient maintenance group, the cumulative crude relapse rate was 22.7% and the cumulative modified crude relapse rate was 50.0%. The median time to relapse was 20 weeks for the vitamin E group and 18.7 weeks for the emollient group. Once VLS has been stabilized with topical corticosteroids, long-term treatment with both vitamin E and emollients may be considered in maintain LS remission.

  20. Mometasone Nasal Spray

    ... nausea, or vomiting nosebleeds headache sore throat increased menstrual pain muscle or joint pain sinus pain weakness diarrhea ... weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and ...

  1. Induction of interleukin-6 by ionizing radiation in a human epithelial cell line. Modulation by corticosteroids

    Beetz, A.; Oppel, T.; Lu-Hesselmann, J.; Peter, R.U. [Federal Armed Forces Medical Academy, Munich (Germany). Institute of Radiobiology; Messer, G.; Kind, P.; Peter, R.U. [Munich Univ., Ludwig-Maximilians (Germany). Dept. of Dermatology

    1997-03-01

    To overcome the detrimental effects of an uncontrolled rise of pro-inflammatory cytokines as an acute response to ionizing radiations, therapeutic drugs capable of inhibiting the pathway leading to transcriptional activation of cytokine genes are of particular interest. Here is described the potency of hydrocortisone, dexamethasone and mometasone furoate to inhibit radiation-induced IL-6 (interleukin) expression. Mometasone furoate and dexamethasone were shown to be much more effective than hydrocortisone. Finally, the reported low atrophogenic potential of mometasone furoate after topical application, together with the strongest capacity of IL-6 down-regulation in ionizing radiations treated cells points to this drug as the most promising derivative of the three investigated corticosteroids. (N.C.)

  2. Using Six Sigma to improve once daily gentamicin dosing and therapeutic drug monitoring performance.

    Egan, Sean

    2012-08-07

    BACKGROUND: Safe, effective therapy with the antimicrobial gentamicin requires good practice in dose selection and monitoring of serum levels. Suboptimal therapy occurs with breakdown in the process of drug dosing, serum blood sampling, laboratory processing and level interpretation. Unintentional underdosing may result. This improvement effort aimed to optimise this process in an academic teaching hospital using Six Sigma process improvement methodology. METHODS: A multidisciplinary project team was formed. Process measures considered critical to quality were defined, and baseline practice was examined through process mapping and audit. Root cause analysis informed improvement measures. These included a new dosing and monitoring schedule, and standardised assay sampling and drug administration timing which maximised local capabilities. Three iterations of the improvement cycle were conducted over a 24-month period. RESULTS: The attainment of serum level sampling in the required time window improved by 85% (p≤0.0001). A 66% improvement in accuracy of dosing was observed (p≤0.0001). Unnecessary dose omission while awaiting level results and inadvertent disruption to therapy due to dosing and monitoring process breakdown were eliminated. Average daily dose administered increased from 3.39 mg\\/kg to 4.78 mg\\/kg\\/day. CONCLUSIONS: Using Six Sigma methodology enhanced gentamicin usage process performance. Local process related factors may adversely affect adherence to practice guidelines for gentamicin, a drug which is complex to use. It is vital to adapt dosing guidance and monitoring requirements so that they are capable of being implemented in the clinical environment as a matter of routine. Improvement may be achieved through a structured localised approach with multidisciplinary stakeholder involvement.

  3. Once-daily transdermal rivastigmine in the treatment of Alzheimer’s disease

    Andreas Wentrup

    2008-11-01

    Full Text Available Andreas Wentrup, Wolfgang H Oertel, Richard DodelDepartment of Neurology, Philipps-University Marburg, GermanyAbstract: During the past decade, transdermal delivery systems (TDS have become increasingly important for treating neurologic and psychiatric disorders. The rivastigmine patch was the first patch to be approved to treat Alzheimer’s disease (AD. The 9.5 mg/24 h patch has equal efficacy to the capsules and reduces gastrointestinal adverse events, such as nausea and vomiting, by two-thirds. This treatment is well tolerated by patients because drug delivery is even and continuous, reducing fluctuation in drug plasma level, and attenuating the development of centrally mediated cholinergic side effects. Furthermore, once-a-day application of the patch enables an easy treatment schedule, ease of handling, infrequent skin irritations, and a patient- and caregiver-friendly mode of administration. Improved compliance with a subsequent drug administration may contribute to better clinical efficacy, reduce caregiver burden, result in a slower rate of institutionalization, and lead to a decrease in healthcare and medical costs. Because of these advantages, the rivastigmine patch has enabled great progress in the treatment of AD, and represents an excellent alternative to the orally administered cholinesterase inhibitors.Keywords: Alzheimer’s disease, rivastigmine, patch, dementia

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

    Ulrik, Charlotte Suppli

    2012-01-01

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

  5. Once Daily Valacyclovir for Reducing Viral Shedding in Subjects Newly Diagnosed with Genital Herpes

    Mark G. Martens

    2009-01-01

    Results. 52 subjects had at least one PCR measurement in both treatment periods and comprised the primary efficacy population. Valacyclovir significantly reduced HSV-2 shedding during all days compared to placebo (mean 2.9% versus 13.5% of all days (P<.01, a 78% reduction. Valacyclovir significantly reduced subclinical HSV-2 shedding during all days compared to placebo (mean 2.4% versus 11.0% of all days (P<.01, a 78% reduction. However, 79% of subjects had no GH recurrences while receiving valacyclovir compared to 52% of subjects receiving placebo (P<.01. Conclusion. In this study, the frequency of total and subclinical HSV-2 shedding was greater than reported in earlier studies involving subjects with a history of symptomatic genital recurrences. Our study is the first to demonstrate a significant reduction in viral shedding with valacyclovir 1 g daily compared to placebo in a population of subjects newly diagnosed with HSV-2 infection.

  6. Clinical potential of lixisenatide once daily treatment for type 2 diabetes mellitus

    Petersen, Andreas Brønden; Christensen, Mikkel

    2013-01-01

    The glucagon-like peptide (GLP)-1 receptor agonist lixisenatide (Lyxumia(®)) was approved for marketing by the European Medicines Agency in February 2013 and has been evaluated in a clinical study program called GetGoal. Lixisenatide activates the GLP-1 receptor and thereby exercises the range of...... of lixisenatide seems to be in combination with basal insulin. A large multicenter study will determine the future potential of lixisenatide in preventing cardiovascular events and mortality, in patients with type 2 diabetes and recent acute coronary syndrome....

  7. Efficacy and safety of ciclesonide once daily and fluticasone propionate twice daily in children with asthma

    Pedersen, Søren; Engelstätter, Renate; Weber, Hans-Jochen

    2009-01-01

    BACKGROUND: Ciclesonide is a new inhaled corticosteroid (ICS). Information about its clinical efficacy and safety in relation to other ICS in children is needed for clinical positioning. OBJECTIVE: This 12-week, randomized, double-blind, double-dummy, three-arm, parallel-group study compared the ...

  8. Development and in-vitro Evaluation of Once Daily Tablet Dosage ...

    Kuksal A, Tiwary AK, Jain NK, Jain S. Formulation and in vitro, in vivo evaluation of extended-release matrix tablet of zidovudine: influence of combination of hydrophilic and hydrophobic matrix formers. AAPS,. Pharm Sci Tech 2006; 7: 1-9. 6. Kumar R, Patil S, Patil MB, Patil SR, Paschapur MS. Design and In vitro Evaluation ...

  9. Role of once-daily glycopyrronium bromide (NVA237 in the management of COPD

    D’Urzo A

    2013-08-01

    Full Text Available Anthony D'UrzoDepartment of Family and Community Medicine, University of Toronto, Toronto, ON, CanadaAbstract: Progressive airflow limitation is a hallmark feature of chronic obstructive pulmonary disease (COPD that ultimately leads to breathlessness, impaired quality of life, and reduced exercise capacity. Pharmacotherapy is used in patients with COPD to prevent and control symptoms, reduce both the frequency and severity of exacerbations, improve health status, and increase exercise tolerance. These strategies are intended to address management issues which promote both current disease control and a reduction in the risk of disease deterioration in the future. At the present time, long-acting β2-agonists (LABAs and long-acting muscarinic antagonists (LAMAs are available for maintenance therapy in patients with persistent symptoms. Tiotropium was the first LAMA to be approved for management of COPD, and many studies have described its beneficial effects on multiple clinically relevant outcomes. Glycopyrronium bromide (NVA237, a new LAMA, has been developed and received regulatory approval for management of COPD in a number of countries around the world. Results from pivotal Phase III trials suggest that NVA237 is safe and well tolerated in patients with moderate to severe COPD, and provides rapid and sustained improvements in lung function. Further, these changes are associated with statistically and clinically meaningful improvements in dyspnea, health-related quality of life, and exercise tolerance. Treatment with NVA237 also results in a significant reduction in risk of exacerbations and the need for rescue medication, and has been comparable with tiotropium with respect to safety and efficacy outcomes. Finally, emerging data indicate that NVA237 is efficacious both as monotherapy and in combination with indacaterol.Keywords: glycopyrronium bromide, NVA237, chronic obstructive pulmonary disease, inhaled long-acting bronchodilators

  10. New developments in the treatment of rosacea – role of once-daily ivermectin cream

    Cardwell LA

    2016-03-01

    Full Text Available Leah A Cardwell,1 Hossein Alinia,1 Sara Moradi Tuchayi,1 Steven R Feldman,1–31Department of Dermatology, Center for Dermatology Research, 2Department of Pathology, 3Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA Abstract: Rosacea is a chronic dermatological disorder with a variety of clinical manifestations localized largely to the central face. The unclear etiology of rosacea fosters therapeutic difficulty; however, subtle clinical improvement with pharmacologic treatments of various drug categories suggests a multifactorial etiology of the disease. Factors that may contribute to disease pathogenesis include immune abnormality, vascular abnormality, neurogenic dysregulation, presence of cutaneous microorganisms, UV damage, and skin barrier dysfunction. The role of ivermectin in the treatment of rosacea may be as an anti-inflammatory and anti-parasitic agent targeting Demodex mites. In comparing topical ivermectin and metronidazole, ivermectin was more effective; this treatment modality boasted more improved quality of life, reduced lesion counts, and more favorable participant and physician assessment of disease severity. Patients who received ivermectin 1% cream had an acceptable safety profile. Ivermectin is efficacious in decreasing inflammatory lesion counts and erythema. Keywords: papulopustular rosacea, topical ivermectin, metronidazole, azelaic acid, topical

  11. Comparison of Provider-Assessed and Patient-Reported Outcome Measures of Acute Skin Toxicity During a Phase III Trial of Mometasone Cream Versus Placebo During Breast Radiotherapy: The North Central Cancer Treatment Group (N06C4)

    Neben-Wittich, Michelle A.; Atherton, Pamela J.; Schwartz, David J.; Sloan, Jeff A.; Griffin, Patricia C.; Deming, Richard L.; Anders, Jon C.; Loprinzi, Charles L.; Burger, Kelli N.; Martenson, James A.; Miller, Robert C.

    2011-01-01

    Purpose: Considerable interobserver variability exists among providers and between providers and patients when measuring subjective symptoms. In the recently published Phase III N06C4 trial of mometasone cream vs. placebo to prevent radiation dermatitis, the primary provider-assessed (PA) endpoint, using the Common Toxicity Criteria for Adverse Events (CTCAE), was negative. However, prospectively planned secondary analyses of patient-reported outcomes (PROs), using the Skindex-16 and Skin Toxicity Assessment Tool (STAT), were positive. This study assesses the relationship between PA outcomes and PROs. Methods and Materials: Pearson correlation coefficients were calculated to compare the three tools. Statistical correlations were defined as follows: 0.7, strong. Results: CTCAE dermatitis moderately correlated with STAT erythema, and CTCAE pruritus strongly correlated with STAT itching. CTCAE pruritus had a moderate correlation with Skindex-16 itching. Comparing the 2 PRO tools, Skindex-16 itching correlated moderately with STAT itching. Skindex-16 burning, hurting, irritation, and persistence all showed the strongest correlation with STAT burning; they showed moderate correlations with STAT itching and tenderness. Conclusions: The PRO Skindex-16 correlated well with the PRO portions of STAT, but neither tool correlated well with CTCAE. PROs delineated a wider spectrum of toxicity than PA measures and provided more information on rash, redness, pruritus, and annoyance measures compared with CTCAE findings of rash and pruritus. PROs may provide a more complete measure of patient experience than single-symptom, PA endpoints in clinical trials assessing radiation skin toxicity.

  12. Action of topical mometasone on the pigmented halos of micrografting in patients with vitiligo Ação da mometasona tópica nos halos pigmentares de microenxertia em vitiligo

    Karine Dantas Diógenes Saldanha

    2012-10-01

    Full Text Available BACKGROUND: Vitiligo is a prevalent skin pigmentation disorder worldwide. The treatments available still offer limited results to some patients. For patients with clinically stable vitiligo, melanocyte transplantation is an appropriate treatment option, and the technique of autologous punch grafting shows good repigmentation. OBJECTIVE: To evaluate the effect of topical mometasone on the halos of repigmentation after autologous punch grafting in patients with clinically stable vitiligo. METHODS: Between 2009 and 2010, 11 patients with clinically stable vitiligo (7 generalized, 2 focal and 2 segmental underwent autologous punch grafting in the achromic patches. According to the clinical type of vitiligo, patients were instructed to use the corticosteroid ointment during 6 months, only on a few grafted lesions. In the first month, the mometasone ointment was used twice a day and after that just once. They were reassessed 1, 3 and 6 months after the procedure. Grafted halos were photographed and recorded using the software fotofinder. After 6 months, all the treated and untreated areas of the repigmentation halos were measured and analyzed comparatively. RESULTS: The median area of the repigmentation halos after 6 months of treatment with mometasone was larger (25,96 mm² than the one of the untreated halos (13,86 mm² , showing a statistically significant difference (p = 0,026. CONCLUSION: In this study, the use of mometasone ointment increased the area of the repigmentation halos after punch grafting. However, this should be further investigated in larger samples in order to validate this positive action in the treatment of stable vitiligo.FUNDAMENTOS: Vitiligo é um transtorno de pigmentação freqüente na população mundial. Seu tratamento ainda oferece resultados limitados em alguns pacientes. Nos casos de vitiligo estável clinicamente, o transplante de melanócitos tornase uma opção terapêutica, sendo a técnica de enxertos aut

  13. Assessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus

    Levy Juliana

    2010-03-01

    Full Text Available Abstract Aims To determine prospectively the efficacy, tolerability and patient satisfaction of an extended release formulation of metformin (metformin XR in hospital based outpatients with type 2 diabetes mellitus currently treated with standard metformin. Methods Patients on immediate release standard metformin either alone or combined with other oral agents were switched to extended release metformin XR 500 mg tablets and titrated to a maximum dose of 2000 mg/day Measurements to include glucose and lipid control, blood pressure, body weight, waist circumference, C-reactive protein, adverse events and patient satisfaction were recorded at baseline, three and six months. Results Complete data were obtained for 35 of the 61 patients enrolled to the study. At three and six months no changes were reported for any of the cardiovascular risk factors except for lipids where there was a modest rise in plasma triglycerides. These effects were achieved with a reduced dose of metformin XR compared to pre-study dosing with standard metformin (1500 mg +/- 402 vs 1861 +/- 711 p = 0.004. A total of 77% of patients were free of gastrointestinal side effects and 83% of patients stated a preference for metformin XR at the end of the study. Ghost tablets were reported in the faeces by the majority of the patients (54.1%. Conclusions Patients switched to extended release metformin XR derived the same clinical and metabolic benefits as for standard metformin but with reduced dosage, fewer gastrointestinal side effects and a greater sense of well being and satisfaction on medication.

  14. Once-daily glycopyrronium bromide (Seebri Breezhaler(®)) for the treatment of chronic obstructive pulmonary disease (COPD)

    Ulrik, Charlotte Suppli

    2015-01-01

    INTRODUCTION: Long-acting bronchodilators are the mainstay of pharmacological therapy for patients with chronic obstructive pulmonary disease (COPD). The choice of optimal bronchodilator therapy for COPD is increasingly difficult for clinicians as new treatments are marketed. AREAS COVERED: Inhaled...... glycopyrronium bromide (Seebri Breezhaler®) is a well-tolerated long-acting anti-muscarinic agent (LAMA) with a fast onset of action. In patients with moderate to severe COPD, glycopyrronium bromide has clinically important effects on level of FEV1, use of relief medication, day-time dyspnea scores, and probably...... also on health status. Furthermore, glycopyrronium bromide also has beneficial effects on dynamic hyperinflation and, probably by that, exercise tolerance. Glycopyrronium bromide has been shown to reduce the rate of exacerbations in patients with moderate to severe COPD, although as a secondary outcome...

  15. Pharmacokinetics of and short-term virologic response to low-dose 400-milligram once-daily raltegravir maintenance therapy.

    Ananworanich, J.; Gorowara, M.; Avihingsanon, A.; Kerr, S.J.; Heesch, N. van; Khongpetch, C.; Uanithirat, A.; Hill, A.; Ruxrungtham, K.; Burger, D.M.

    2012-01-01

    Because studies showed similar viral suppression with lower raltegravir doses and because Asians usually have high antiretroviral concentrations, we explored low-dose raltegravir therapy in Thais. Nineteen adults on raltegravir at 400 mg twice daily (BID) with HIV RNA loads of <50 copies/ml were

  16. Once-daily fosamprenavir with ritonavir in the treatment of HIV infection in therapy-naïve patients

    Gisslen, Magnus; Flamholc,Leo; Gisslen,Magnus

    2008-01-01

    Leo Flamholc1, Magnus Gisslén21Department of Infectious Diseases, Malmö University Hospital, Malmö, Sweden; 2Sahlgrenska University Hospital/Östra, Gothenburg, SwedenAbstract: Treatment options for HIV patients have dramatically improved since the introduction of efficacious antiretroviral combination therapy more than a decade ago. Treatment regimens have been simplified with fewer pills and fewer daily dosages. Fosamprenavir is a protease inhibitor with...

  17. The economics of 4 grams once daily mesalazine dosing compared with 4 grams twice daily in active ulcerative colitis

    Connolly, M.; Kuyvenhoven, J.; Postma, M.; Nielsen, S.

    2013-01-01

    Background: Dosing frequency is an important treatment consideration that has been shown to influence adherence and outcomes when treating ulcerative colitis (UC). In this analysis we evaluate the economic consequences of outcome differences observed in the study comparing mesalazine 4g per day once

  18. Tadalafil once daily: Narrative review of a treatment option for female sexual dysfunctions (FSD in midlife and older women

    Chiara Borghi

    2017-03-01

    Full Text Available Female Sexual Disorders (FSD include a complex, multidimensional, individual experience that can change as an individual age, suggesting that these problems are caused by multiple factors including psychosocial factors, personal relationships, pathologic changes caused by diseases, and pharmacologic influences. Menopause is an important time for middle aged women and postmenopausal physiological changes could have a significant role in the development of FSD. Few is still known about their correct definition and treatment. Their incidence, prevalence and risk factors are difficult to define because of a high level of overlap in the experience of problems with desire, arousal, and orgasm. Little evidences are known about the best therapeutic approach, and both non-pharmacological and pharmacological treatment options have been described. Among these, phosphodiesterase type 5 inhibitors could be an effective option for many subtypes of female sexual disorders, with an improvement in different aspects of sexual function, such as desire, arousal, orgasm and sexual satisfaction. In this paper authors reviewed what is already known about the use of these vasoactive agents, particularly tadalafil, as a treatment option for female sexual disturbances.

  19. Effects of corticosteroids on hyposmia in persistent allergic rhinitis.

    Catana, Iuliu V; Chirila, Magdalena; Negoias, Simona; Bologa, Ramona; Cosgarea, Marcel

    2013-01-01

    To asses the effects of two topical nasal corticosteroids sprays on hyposmia in patients with persistent allergic rhinitis. The study was a prospective clinical trial and it included twenty four patients with persistent allergic rhinitis (PER) and hyposmia (H). The patients were divided into two groups depending on the type of corticosteroid topical nasal spray treatment: group A, 200 micrograms dose of mometasone furoate (MF) and group B, 110 micrograms dose of fluticasone furoate (FF) both administered in the morning for 4 weeks. The olfactory function of the patients was evaluated with the extended Test battery "Sniffin' Sticks". The visual analogue scale (VAS) was used for the assessment of hyposmia, nasal discharge. The level of the nasal obstruction, before and after the treatment, was evaluated through the anterior rhinomanometry. The comparisons between the two types of topical corticosteroids showed a significant improvement separately between scores of the odor threshold (OT), odor discrimination (OD) and odor identification (OI) and also on the final olfactory score (SDI) before and after 4 weeks of the treatment. The comparisons of the VAS scores pre and post treatment showed a significant improvement in hyposmia and nasal obstruction. The nasal airflow and the nasal discharge scores were improved, but the differences were not statistically significant between the groups. The final statistical analysis found no significant differences between the two patients groups. The study concludes that fluticasone furoate and mometasone furoate have quite the same effects on hyposmia and on the classical symptoms from PER.

  20. Molecular and clinical pharmacology of intranasal corticosteroids: clinical and therapeutic implications.

    Derendorf, H; Meltzer, E O

    2008-10-01

    Intranasal corticosteroids (INSs) are effective treatments for allergic rhinitis, rhinosinusitis, and nasal polyposis. In recent years, increased understanding of corticosteroid and glucocorticoid receptor pharmacology has enabled the development of molecules designed specifically to achieve potent, localized activity with minimal risk of systemic exposure. Pharmacologic potency studies using affinity and other assessments have produced similar rank orders of potency, with the most potent being mometasone furoate, fluticasone propionate, and its modification, fluticasone furoate. The furoate and propionate ester side chains render these agents highly lipophilic, which may facilitate their absorption through nasal mucosa and uptake across phospholipid cell membranes. These compounds demonstrate negligible systemic absorption. Systemic absorption rates are higher among the older corticosteroids (flunisolide, beclomethasone dipropionate, triamcinolone acetonide, and budesonide), which have bioavailabilities in the range of 34-49%. Studies, including 1-year studies with mometasone furoate, fluticasone propionate, and budesonide that evaluated potential systemic effects of INSs in children have generally found no adverse effects on hypothalamic-pituitary-adrenal axis function or growth. Clinical data suggest no significant differences in efficacy between the INSs. Theoretically, newer agents with lower systemic availability may be preferable, and may come closer to the pharmacokinetic/pharmacologic criteria for the ideal therapeutic choice.

  1. Comparison of vildagliptin twice daily vs. sitagliptin once daily using continuous glucose monitoring (CGM: Crossover pilot study (J-VICTORIA study

    Sakamoto Masaya

    2012-08-01

    Full Text Available Abstract Background No previous studies have compared the DPP-4 inhibitors vildagliptin and sitagliptin in terms of blood glucose levels using continuous glucose monitoring (CGM and cardiovascular parameters. Methods Twenty patients with type 2 diabetes mellitus were randomly allocated to groups who received vildagliptin then sitagliptin, or vice versa. Patients were hospitalized at 1 month after starting each drug, and CGM was used to determine: 1 mean (± standard deviation 24-hour blood glucose level, 2 mean amplitude of glycemic excursions (MAGE, 3 fasting blood glucose level, 4 highest postprandial blood glucose level and time, 5 increase in blood glucose level after each meal, 6 area under the curve (AUC for blood glucose level ≥180 mg/dL within 3 hours after each meal, and 7 area over the curve (AOC for daily blood glucose level Results The mean 24-hour blood glucose level was significantly lower in patients taking vildagliptin than sitagliptin (142.1 ± 35.5 vs. 153.2 ± 37.0 mg/dL; p = 0.012. In patients taking vildagliptin, MAGE was significantly lower (110.5 ± 33.5 vs. 129.4 ± 45.1 mg/dL; p = 0.040, the highest blood glucose level after supper was significantly lower (206.1 ± 40.2 vs. 223.2 ± 43.5 mg/dL; p = 0.015, the AUC (≥180 mg/dL within 3 h was significantly lower after breakfast (484.3 vs. 897.9 mg/min/dL; p = 0.025, and urinary CPR level was significantly higher (97.0 ± 41.6 vs. 85.2 ± 39.9 μg/day; p = 0.008 than in patients taking sitagliptin. There were no significant differences in plasma HbA1c, GA, 1,5AG, IRI, CPR, BNP, or PAI-1 levels between patients taking vildagliptin and sitagliptin. Conclusions CGM showed that mean 24-h blood glucose, MAGE, highest blood glucose level after supper, and hyperglycemia after breakfast were significantly lower in patients with type 2 diabetes mellitus taking vildagliptin than those taking sitagliptin. There were no significant differences in BNP and PAI-1 levels between patients taking vildagliptin and sitagliptin. Trial registration UMIN000007687

  2. Comparison of vildagliptin twice daily vs. sitagliptin once daily using continuous glucose monitoring (CGM): Crossover pilot study (J-VICTORIA study)

    2012-01-01

    Background No previous studies have compared the DPP-4 inhibitors vildagliptin and sitagliptin in terms of blood glucose levels using continuous glucose monitoring (CGM) and cardiovascular parameters. Methods Twenty patients with type 2 diabetes mellitus were randomly allocated to groups who received vildagliptin then sitagliptin, or vice versa. Patients were hospitalized at 1 month after starting each drug, and CGM was used to determine: 1) mean (± standard deviation) 24-hour blood glucose level, 2) mean amplitude of glycemic excursions (MAGE), 3) fasting blood glucose level, 4) highest postprandial blood glucose level and time, 5) increase in blood glucose level after each meal, 6) area under the curve (AUC) for blood glucose level ≥180 mg/dL within 3 hours after each meal, and 7) area over the curve (AOC) for daily blood glucose level vildagliptin than sitagliptin (142.1 ± 35.5 vs. 153.2 ± 37.0 mg/dL; p = 0.012). In patients taking vildagliptin, MAGE was significantly lower (110.5 ± 33.5 vs. 129.4 ± 45.1 mg/dL; p = 0.040), the highest blood glucose level after supper was significantly lower (206.1 ± 40.2 vs. 223.2 ± 43.5 mg/dL; p = 0.015), the AUC (≥180 mg/dL) within 3 h was significantly lower after breakfast (484.3 vs. 897.9 mg/min/dL; p = 0.025), and urinary CPR level was significantly higher (97.0 ± 41.6 vs. 85.2 ± 39.9 μg/day; p = 0.008) than in patients taking sitagliptin. There were no significant differences in plasma HbA1c, GA, 1,5AG, IRI, CPR, BNP, or PAI-1 levels between patients taking vildagliptin and sitagliptin. Conclusions CGM showed that mean 24-h blood glucose, MAGE, highest blood glucose level after supper, and hyperglycemia after breakfast were significantly lower in patients with type 2 diabetes mellitus taking vildagliptin than those taking sitagliptin. There were no significant differences in BNP and PAI-1 levels between patients taking vildagliptin and sitagliptin. Trial registration UMIN000007687 PMID:22867630

  3. Ketoconazole is inferior to ritonavir as an alternative booster for saquinavir in a once daily regimen in Thai HIV-1 infected patients

    Autar, Reshma Saskia; Wit, Ferdinand W. N. M.; Sankote, Jongkol; Sutthichom, Duanghathai; Kimenai, Elly; Hassink, Elly; Hill, Andrew; Cooper, David A.; Phanuphak, Praphan; Lange, Joep M. A.; Burger, David M.; Ruxrungtham, Kiat

    2007-01-01

    OBJECTIVE: To improve the pharmacokinetics of protease inhibitors, boosting with low-dose ritonavir is performed. However, toxicity, storage conditions and high costs of antiretroviral treatment may necessitate interruption of ritonavir. Ketoconazole was investigated as a potential booster of

  4. Ketoconazole is inferior to ritonavir as an alternative booster for saquinavir in a once daily regimen in Thai HIV-1 infected patients.

    Autar, R.S.; Wit, F.W.; Sankote, J.; Sutthichom, D.; Kimenai, E.; Hassink, E.A.M.; Hill, A.; Cooper, D.A.; Phanuphak, P.; Lange, J.M.A.; Burger, D.M.; Ruxrungtham, K.

    2007-01-01

    OBJECTIVE: To improve the pharmacokinetics of protease inhibitors, boosting with low-dose ritonavir is performed. However, toxicity, storage conditions and high costs of antiretroviral treatment may necessitate interruption of ritonavir. Ketoconazole was investigated as a potential booster of

  5. Clinical trial: lansoprazole 15 or 30 mg once daily vs. placebo for treatment of frequent nighttime heartburn in self-treating subjects.

    Peura, D A; Riff, D S; Snoddy, A M; Fennerty, M B

    2009-09-01

    Frequent nighttime heartburn is common. Lansoprazole 15 mg is indicated for treatment of heartburn and other gastro-oesophageal reflux disease-related symptoms. To evaluate the efficacy and safety of lansoprazole in self-treating subjects with frequent nocturnal heartburn. A total of 864 subjects with heartburn on >or=2 days/week over the past month were randomized to double-blind treatment with lansoprazole 15 or 30 mg or placebo each morning. Endpoints were percentage of night times without heartburn (primary), percentage of 24-h days without heartburn and percentage of subjects without heartburn on day 1. Mean percentage of night times without heartburn was significantly greater with lansoprazole 15 mg (61.3%) or lansoprazole 30 mg (61.7%) vs. placebo (47.8%) over 14 days (P heartburn and percentage of subjects without heartburn on day 1 were significantly greater with lansoprazole 15 or 30 mg vs. placebo. Both lansoprazole 15 and 30 mg were highly effective and well tolerated in reducing symptoms in subjects with frequent nighttime heartburn. The benefit of therapy on 24-h heartburn and nighttime heartburn on day 1 of treatment was also evident. Lansoprazole 15 mg is a suitable choice for management of frequent nighttime heartburn.

  6. Concentrations of Dapivirine in the Rhesus Macaque and Rabbit following Once Daily Intravaginal Administration of a Gel Formulation of [14C]Dapivirine for 7 Days▿

    Nuttall, Jeremy P.; Thake, Daryl C.; Lewis, Mark G.; Ferkany, John W.; Romano, Joseph W.; Mitchnick, Mark A.

    2007-01-01

    Dapivirine is a nonnucleoside reverse transcriptase inhibitor being developed as a topical microbicide for the prevention of human immunodeficiency virus infection. The distribution of radioactivity and drug in plasma and in vaginal, cervical, and draining lymph node tissues was investigated after daily application of a vaginal gel formulation of [14C]dapivirine to rhesus macaques. This was preceded by a preliminary study with rabbits. Following the intravaginal administration of [14C]dapivir...

  7. Safety and tolerability of once-daily tiotropium Respimat(®) as add-on to at least inhaled corticosteroids in adult patients with symptomatic asthma

    Dahl, Ronald; Engel, Michael; Dusser, Daniel

    2016-01-01

    BACKGROUND: Tiotropium, a long-acting anticholinergic bronchodilator, has demonstrated efficacy and safety as add-on therapy to inhaled corticosteroids (ICS), with or without other maintenance therapies, in patients with symptomatic asthma. OBJECTIVE: To evaluate safety and tolerability of tiotro...

  8. Switching from NPH insulin to once-daily insulin detemir in basal-bolus-treated patients with diabetes mellitus: data from the European cohort of the PREDICTIVE study.

    Sreenan, S

    2008-12-01

    The PREDICTIVE study is a multinational observational study designed to follow up patients with diabetes who started insulin detemir (IDet) in routine care. Recruitment started in June 2004 and is ongoing in some countries.

  9. Long term effectiveness of once-daily unboosted atazanavir plus abacavir/lamivudine as a switch strategy in subjects with virological suppression

    Llibre, Josep M; Cozzi-Lepri, Alessandro; La Rosa, Jorge Antonio Valencia

    2014-01-01

    routine however are scant. METHODS: We evaluated treatment outcomes of ATV400+ABC/3TC in pre-treated subjects in the EuroSIDA cohort with undetectable HIV-1 RNA, and previous ABC experience or assumed previous HLA B57*01 testing. We performed a time to loss of virologic response (TLOVR below 50 c...

  10. Atomoxetine once daily for 24 weeks in adults with attention-deficit/hyperactivity disorder (ADHD): impact of treatment on family functioning.

    Wietecha, Linda; Young, Joel; Ruff, Dustin; Dunn, David; Findling, Robert L; Saylor, Keith

    2012-01-01

    To assess the efficacy of atomoxetine (ATX) and impact of treatment on family functioning in adults with ADHD. Adults with attention-deficit/hyperactivity disorder (ADHD) having both a spouse/partner and child were randomized to placebo (n = 234) or ATX (n = 268) for 24 weeks. Attention-deficit/hyperactivity disorder measures included the Conners Adult ADHD Rating Scale total ADHD Symptoms score and Clinical Global Impression-ADHD-Severity. Marital measures included the Dyadic Adjustment Scale and the Family Assessment Measure Dyadic Relationship Scale (FAM III). Parenting measures included the Parenting Stress Index, Alabama Parenting Questionnaire, and Parenting Sense of Competence Scale (PSCS). Improvement was greater with ATX over placebo at 24 weeks on the Conners Adult ADHD Rating Scale (-16.43 vs -8.65; P ADHD yielded significant interaction and treatment differences for the FAM III Task Accomplishment and the FAM III and Dyadic Adjustment Scale affective expression items, PSCS total score, Alabama Parenting Questionnaire Corporal Punishment, and Parenting Stress Index attachment items. Atomoxetine demonstrated significant ADHD symptom reduction over 24 weeks. Although both groups demonstrated baseline-to-end point changes on many marital and parenting measure items, there were no treatment differences. Maladaptive behaviors of long-standing ADHD may benefit from both medication and behavioral-psychosocial intervention.

  11. The Salford Lung Study protocol: a pragmatic, randomised phase III real-world effectiveness trial in asthma

    Woodcock, Ashley; Bakerly, Nawar Diar; New, John P.; Gibson, J. Martin; Wu, Wei; Vestbo, J?rgen; Leather, David

    2015-01-01

    Background Novel therapies need to be evaluated in normal clinical practice to allow a true representation of the treatment effectiveness in real-world settings. Methods/design The Salford Lung Study is a pragmatic randomised controlled trial in adult asthma, evaluating the clinical effectiveness and safety of once-daily fluticasone furoate (100??g or 200??g)/vilanterol 25??g in a novel dry-powder inhaler, versus existing asthma maintenance therapy. The study was initiated before this investi...

  12. TREATMENT OF CHILDREN'S ALLERGIC CONJUNCTIVITIS

    L.D. Ksenzova

    2008-01-01

    Full Text Available Allergic conjunctivitis is a widely spread disease, which is often accompanied with an allergic rhinitis. According to the up to date recommendations, the treatment of the allergic rhino conjunctivitis is based on 3 key principles: elimination of the allergen, conducting an allergen targeted immunotherapy and pharmacotherapy. The medication treatment of the allergic rhino conjunctivitis should include antihistamines of the 2nd generation and/or intranasal corticosteroids. Their effectiveness was proven with the findings of numerous place controlled surveys; in most cases they are safe. The usage experience of the intranasal formulation of mometasone furoate (Nasonex shows that with a minimal biological availability of the medication and the absence of its influence upon the «hypothalamus–hypophysis–adrenal glands» system and growth of children, mometasone can be a medication of choice to treat children's rhino conjunctivitis.Key words: children, allergic conjunctivitis, treatment.

  13. Drug repurposing from an academic perspective

    Oprea, Tudor; Bauman, Julie E.; Bologa, Cristian G.

    2011-01-01

    Academia and small business research units are poised to play an increasing role in drug discovery, with drug repurposing as one of the major areas of activity. Here we summarize project status for several drugs or classes of drugs: raltegravir, cyclobenzaprine, benzbromarone, mometasone furoate...... intellectual coverage and issues related to dosing and safety may lead to significant drawbacks. The development of a more streamlined regulatory process worldwide, and the development of precompetitive knowledge transfer systems such as a global healthcare database focused on regulatory and scientific...

  14. Anti-Inflammatory Effect of IL-37b in Children with Allergic Rhinitis

    Wenlong Liu

    2014-01-01

    Full Text Available Background. Interleukin-37 (IL-37, a newly described member of IL-1family, functioned as a fundamental inhibitor of innate inflammatory and immune responses, especially its isoform IL-37b. Objective. This study was undertaken to evaluate the expression and regulation of IL-37b in children with allergic rhinitis (AR. Methods. Forty children with AR and twenty-five normal controls were included. The relationship between IL-37b and Th1/2 cytokines production in serum and nasal lavage was examined by enzyme-linked immunosorbent assay (ELISA. Peripheral blood mononuclear cells (PBMCs were purified for in vitro regulation experiment of IL-37b. Intranasal mometasone furoate was given in AR children and IL-37b change after one-month treatment was detected using ELISA. Results. We observed significantly decreased IL-37b expression levels in both serum and nasal lavage compared to controls. IL-37b was negatively correlated with Th2 cytokines. Our results also showed that IL-37b downregulated Th2 cytokine expressed by PBMCs and this modulation was through mitogen-activated protein kinase (MAPK and phosphatidylinositol 3-kinase (PI3K pathway. We also found that intranasal mometasone furoate therapy can promote nasal IL-37b expression. Conclusion. IL-37b may be involved in Th2 cytokine regulation in AR and its expression was related to the efficacy of intranasal steroid therapy.

  15. ROLE OF INTRANASAL STEROIDAL SPRAY IN SEASONAL ALLERGIC RHINITIS WITH OCULAR SYMPTOMS

    Vineel Muppidi

    2017-06-01

    Full Text Available BACKGROUND The eye is especially susceptible to the symptoms of allergic rhinitis, itching (pruritus, tearing (epiphora and redness (erythema because it lacks a mechanical barrier that could prevent the deposition of allergens, such as pollen on the conjunctival surface. These ocular symptoms have been described as examples of the type 1 immediate hypersensitivity reaction. A number of recently published clinical studies apparently support the positive effect of intranasal steroidal sprays on ocular allergy symptoms. The aim of the study is to evaluate the role of intranasal steroids in relieving ocular symptoms in allergic rhinitis. MATERIALS AND METHODS 60 subjects who had seasonal allergic rhinitis with ocular symptoms came to Outpatient Department of Chalmeda Anand Rao Hospital in the year 2015-2016. Randomly, each intranasal steroid is given to 12 patients to a total of 60 patients for 4 weeks 2 puffs in each nostril twice daily and the clinical response is observed. RESULTS A subjective improvement in ocular symptoms was observed in 11 of the 12 patients treated with fluticasone furoate, 8 of 12 patients with fluticasone propionate, 7 of the 12 patients with mometasone furoate, 6 of the 12 patients with beclomethasone and 6 of the 12 patients with budesonide. CONCLUSION Intranasal corticosteroids, which are used for seasonal allergic rhinitis with ocular symptoms are effective in controlling of ocular symptoms. Among these, intranasal corticosteroids, which are used for allergic rhinitis, fluticasone furoate is more effective in relieving ocular symptoms in our study.

  16. An aqueous gel fixed combination of clindamycin phosphate 1.2% and benzoyl peroxide 3.75% for the once-daily treatment of moderate to severe acne vulgaris.

    Pariser, David M; Rich, Phoebe; Cook-Bolden, Fran E; Korotzer, Andrew

    2014-09-01

    To evaluate efficacy, safety, and tolerability of a fixed combination clindamycin phosphate 1.2% and benzoyl peroxide 3.75% (clindamycin-BP 3.75%) aqueous gel in moderate to severe acne vulgaris. A total of 498 patients, 12-40 years of age, were randomized to receive clindamycin-BP 3.75% or vehicle in a double-blind, controlled 12-week, 2-arm study evaluating safety and efficacy using inflammatory and noninflammatory lesion counts, Evaluator Global Severity Scores (EGSS) and subject self-assessment (SSA). In addition, patients completed a patient satisfaction survey (PSS), acne-specific QoL questionnaire, and assessed their facial skin for shininess/oiliness. Clindamycin-BP 3.75% demonstrated statistical superiority to vehicle in reducing both inflammatory and noninflammatory lesions and acne severity. Clindamycin-BP 3.75% showed greater efficacy relative to vehicle in assessments of skin oiliness, SSA and PSS. No substantive differences were seen in cutaneous tolerability among treatment groups and no patients discontinued treatment with Clindamycin-BP 3.75% because of adverse events. Data from controlled studies may differ from clinical practice. It is not possible to determine the contributions from the individual active ingredients. Clindamycin-BP 3.75% provides statistically significant greater efficacy than vehicle with a favorable safety and tolerability profile.

  17. Rivaroxaban-once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation: rationale and design of the ROCKET AF study

    NN, NN

    2010-01-01

    BACKGROUND: Atrial fibrillation (AF), the most common significant cardiac arrhythmia, increases the risk of stroke, particularly in the elderly. Warfarin is effective in reducing stroke risk but is burdensome to patients and is difficult to control. Rivaroxaban is an oral direct factor Xa inhibit...

  18. Insulin Degludec/Insulin Aspart Administered Once Daily at Any Meal, With Insulin Aspart at Other Meals Versus a Standard Basal-Bolus Regimen in Patients With Type 1 Diabetes

    Hirsch, Irl B.; Bode, Bruce; Courreges, Jean-Pierre; Dykiel, Patrik; Franek, Edward; Hermansen, Kjeld; King, Allen; Mersebach, Henriette; Davies, Melanie

    2012-01-01

    OBJECTIVE To evaluate efficacy and tolerability of a co-formulation of insulin degludec and insulin aspart (IDegAsp) with insulin aspart (IAsp) at other meals compared with basal-bolus therapy using insulin detemir (IDet) and IAsp. RESEARCH DESIGN AND METHODS Adults (n = 548) with type 1 diabetes (A1C 7.0–10.0%; BMI ≤35.0 kg/m2) were randomized 2:1 in a 26-week, multinational, parallel-group, treat-to-target trial to IDegAsp or IDet. IDegAsp was given with a meal, and IDet was given in the evening, with a second (breakfast) dose added if needed. RESULTS Non-inferiority for IDegAsp versus IDet was confirmed; A1C improved by 0.75% with IDegAsp and 0.70% with IDet to 7.6% in both groups (estimated treatment difference IDegAsp − IDet: –0.05% [95% CI –0.18 to 0.08]). There was no statistically significant difference between IDegAsp and IDet in the rates of severe hypoglycemia (0.33 and 0.42 episodes/patient-year, respectively) or overall confirmed (plasma glucose <3.1 mmol/L) hypoglycemia (39.17 and 44.34 episodes/patient-year, respectively). Nocturnal confirmed hypoglycemia rate was 37% lower with IDegAsp than IDet (3.71 vs. 5.72 episodes/patient-year, P < 0.05). Weight gain was 2.3 and 1.3 kg with IDegAsp and IDet, respectively (P < 0.05). Total insulin dose was 13% lower in the IDegAsp group (P < 0.0001). No treatment differences were detected in Health-Related Quality of Life, laboratory measurements, physical examination, vital signs, electrocardiograms, fundoscopy, or adverse events. CONCLUSIONS IDegAsp in basal-bolus therapy with IAsp at additional mealtimes improves overall glycemic control and was non-inferior to IDet, with a reduced risk of nocturnal hypoglycemia and fewer injections in comparison with IDet + IAsp basal-bolus therapy. PMID:22933438

  19. Efficacy and safety of a once-daily single-tablet regimen of tenofovir, lamivudine, and efavirenz assessed at 144 weeks among antiretroviral-naïve and experienced HIV-1-infected Thai adults

    Anchalee Avihingsanon

    2017-08-01

    Conclusions: This generic STR TDF/3TC/EFV is effective and well-tolerated. These findings lend support to the use of this generic STR as first-line antiretroviral therapy in resource-limited settings.

  20. A proof-of-concept study of short-cycle intermittent antiretroviral therapy with a once-daily regimen of didanosine, lamivudine, and efavirenz for the treatment of chronic HIV infection

    Dybul, M; Nies-Kraske, E; Dewar, R; Maldarelli, F; Hallahan, CW; Daucher, M; Piscitelli, SC; Ehler, L; Weigand, A; Palmer, S; Metcalf, JA; Davey, RT; Kress, DMR; Powers, A; Beck, [No Value; Frenkel, L; Baseler, M; Coffin, J; Fauci, AS

    2004-01-01

    Background. We previously demonstrated that short-cycle structured intermittent therapy ( SIT; 7 days without therapy followed by 7 days with antiretroviral therapy [ART]) with a ritonavir-boosted, indinavir-based, twice-daily regimen maintained suppression of plasma HIV viremia while reducing serum

  1. Early interventional treatment with intranasal corticosteroids compared with postonset treatment in pollinosis.

    Higaki, Takaya; Okano, Mitsuhiro; Makihara, Seiichiro; Fujiwara, Tazuko; Haruna, Takenori; Noda, Yohei; Kariya, Shin; Nishizaki, Kazunori

    2012-12-01

    The usefulness of early interventional treatment (EIT) with intranasal corticosteroids (INSs) compared with postonset treatment (POT) has not been clarified. To study the efficacy and safety of EIT with INSs compared with POT and placebo in Japanese cedar/cypress pollinosis. We designed a 3-armed, double-blinded, randomized, placebo-controlled trial. Patients received mometasone furoate nasal spray (EIT group: n = 25), placebo (n = 25), or 4 weeks of placebo followed by 8 weeks of mometasone (POT group: n = 25) for a 12-week period starting on February 1, 2011. The primary end point was the comparison of the total nasal symptom score (TNSS) among the 3 groups. Total ocular symptom score (TOSS), total naso-ocular symptom score (TSS), Allergic Rhinitis and Its Impact (ARIA) on Asthma classification, and safety were the main secondary end points. The placebo and POT groups, but not the EIT group, had a significant exacerbation of TNSS and TOSS soon after the start of pollen counts being high on consecutive days. The 12-week mean TSS in the EIT group (score, 2.3) was significantly lower than in the placebo (5.0; P INSs is superior to POT in controlling pollinosis. Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  2. The Salford Lung Study protocol: a pragmatic, randomised phase III real-world effectiveness trial in chronic obstructive pulmonary disease.

    Bakerly, Nawar Diar; Woodcock, Ashley; New, John P; Gibson, J Martin; Wu, Wei; Leather, David; Vestbo, Jørgen

    2015-09-04

    New treatments need to be evaluated in real-world clinical practice to account for co-morbidities, adherence and polypharmacy. Patients with chronic obstructive pulmonary disease (COPD), ≥ 40 years old, with exacerbation in the previous 3 years are randomised 1:1 to once-daily fluticasone furoate 100 μg/vilanterol 25 μg in a novel dry-powder inhaler versus continuing their existing therapy. The primary endpoint is the mean annual rate of COPD exacerbations; an electronic medical record allows real-time collection and monitoring of endpoint and safety data. The Salford Lung Study is the world's first pragmatic randomised controlled trial of a pre-licensed medication in COPD. Clinicaltrials.gov identifier NCT01551758.

  3. The influence of the preparations with the glucocorticosteroids and ceramides on the morphological state of the rats’ skin with the nonspecific dermatitis

    Ya. O. Butko

    2013-04-01

    Full Text Available Introduction. Local therapy is an important method for treatment of dermatitis used to suppress the skin inflammation and the main related symptoms: hyperemia, edema, pruritus, lichenification etc. However today it is important to pay more attention to elimination of the skin dryness, restoration of the damaged epithelium and improvement of the skin barrier functions in dermatitis therapy. Considering all the requirements mentioned above, cream and ointment that correspond to the modern requirements of the local therapy were developed. They promote the decrease of inflammatory processes in skin (Mometasone furoate and Methylprednisolone atseponat are strong GCS with antipruritic, anti-inflammatory, vasoconstrictive, antiproliferative action and with minimum side effects, eliminate excessive skin dryness, restore the damaged epithelium, improve the skin condition and normalize the barrier functions of the skin (ceramides are the natural ceramides of the human’s skin. The purpose of this work was morphological study of the rats’ skin during treatment with cream “Mometasone with ceramides” and ointment “Methyl­prednisolone with ceramides” in the conditions of contact dermatitis inducted by turpentine. Materials and methods. Skin of animals was an object of the research after its treatment with cream “Mometasone with ceramides” and ointment “Methylprednisolone with ceramides”. The comparator preparations were cream “Elocom” and ointment “Advantan”. In the experiment 36 rats divided into groups were used. All the preparations were applied on the skin in a thin layer once a day. After the 5th day of the treatment animals were taken out of the experiment and all the tissue materials were fixed in 10% solution of formalin for morphological studies carrying out. Sections were stained with hematoxylin and eosine. An examination was carried out under the microscope Micros 400. Results of the research. The results showed that

  4. The Salford Lung Study protocol: a pragmatic, randomised phase III real-world effectiveness trial in asthma.

    Woodcock, Ashley; Bakerly, Nawar Diar; New, John P; Gibson, J Martin; Wu, Wei; Vestbo, Jørgen; Leather, David

    2015-12-10

    Novel therapies need to be evaluated in normal clinical practice to allow a true representation of the treatment effectiveness in real-world settings. The Salford Lung Study is a pragmatic randomised controlled trial in adult asthma, evaluating the clinical effectiveness and safety of once-daily fluticasone furoate (100 μg or 200 μg)/vilanterol 25 μg in a novel dry-powder inhaler, versus existing asthma maintenance therapy. The study was initiated before this investigational treatment was licensed and conducted in real-world clinical practice to consider adherence, co-morbidities, polypharmacy, and real-world factors. Asthma Control Test at week 24; safety endpoints include the incidence of serious pneumonias. The study utilises the Salford electronic medical record, which allows near to real-time collection and monitoring of safety data. The Salford Lung Study is the world's first pragmatic randomised controlled trial of a pre-licensed medication in asthma. Use of patients' linked electronic health records to collect clinical endpoints offers minimal disruption to patients and investigators, and also ensures patient safety. This highly innovative study will complement standard double-blind randomised controlled trials in order to improve our understanding of the risk/benefit profile of fluticasone furoate/vilanterol in patients with asthma in real-world settings. Clinicaltrials.gov, NCT01706198; 04 October 2012.

  5. Safety update regarding intranasal corticosteroids for the treatment of allergic rhinitis.

    Blaiss, Michael S

    2011-01-01

    Intranasal corticosteroids (INSs) are the most efficacious medication for the treatment of allergic rhinitis. In 2006, the Joint Task Force of the American College of Allergy, Asthma, and Immunology, and the American Academy of Allergy, Asthma, and Immunology, published a white paper on the potential over-the-counter switch of INS (Bielory L, Blaiss M, Fineman SM, et al. Concerns about intranasal corticosteroids for over-the-counter use: Position statement of the Joint Task Force for the American Academy of Allergy, Asthma and Immunology and the American College of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol 96:514-525, 2006). The concern of the paper was the safety of the use of these agents without oversight by a health care professional. The objective of this paper was to review published literature on the safety of INS since the publication of the task force white paper. Recent studies, which evaluated topical and systemic adverse events associated with ciclesonide (CIC), fluticasone furoate (FF), mometasone furoate (MF), triamcinolone acetonide, fluticasone propionate, budesonide, and beclomethasone dipropionate were summarized. In general, no significant topical or systemic complications were observed in these studies, although none were >1 year in duration. The newer formulations of topical corticosteroids for allergic rhinitis, such as CIC, FF, and MF, which have less systemic bioavailability, may be safer for long-term use. New studies continue to add to the reassurance of the safety of INSs in the treatment of allergic rhinitis but still do not answer the question if these agents are appropriate for long-term use without oversight by a health care professional.

  6. Drug Repurposing from an Academic Perspective.

    Oprea, Tudor I; Bauman, Julie E; Bologa, Cristian G; Buranda, Tione; Chigaev, Alexandre; Edwards, Bruce S; Jarvik, Jonathan W; Gresham, Hattie D; Haynes, Mark K; Hjelle, Brian; Hromas, Robert; Hudson, Laurie; Mackenzie, Debra A; Muller, Carolyn Y; Reed, John C; Simons, Peter C; Smagley, Yelena; Strouse, Juan; Surviladze, Zurab; Thompson, Todd; Ursu, Oleg; Waller, Anna; Wandinger-Ness, Angela; Winter, Stuart S; Wu, Yang; Young, Susan M; Larson, Richard S; Willman, Cheryl; Sklar, Larry A

    2011-01-01

    Academia and small business research units are poised to play an increasing role in drug discovery, with drug repurposing as one of the major areas of activity. Here we summarize project status for a number of drugs or classes of drugs: raltegravir, cyclobenzaprine, benzbromarone, mometasone furoate, astemizole, R-naproxen, ketorolac, tolfenamic acid, phenothiazines, methylergonovine maleate and beta-adrenergic receptor drugs, respectively. Based on this multi-year, multi-project experience we discuss strengths and weaknesses of academic-based drug repurposing research. Translational, target and disease foci are strategic advantages fostered by close proximity and frequent interactions between basic and clinical scientists, which often result in discovering new modes of action for approved drugs. On the other hand, lack of integration with pharmaceutical sciences and toxicology, lack of appropriate intellectual coverage and issues related to dosing and safety may lead to significant drawbacks. The development of a more streamlined regulatory process world-wide, and the development of pre-competitive knowledge transfer systems such as a global healthcare database focused on regulatory and scientific information for drugs world-wide, are among the ideas proposed to improve the process of academic drug discovery and repurposing, and to overcome the "valley of death" by bridging basic to clinical sciences.

  7. Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Effects of Nasal Spray Suspension Particle Size and Properties.

    Rygg, Alex; Hindle, Michael; Longest, P Worth

    2016-04-01

    The objective of this study was to use a recently developed nasal dissolution, absorption, and clearance (DAC) model to evaluate the extent to which suspended drug particle size influences nasal epithelial drug absorption for a spray product. Computational fluid dynamics (CFD) simulations of mucociliary clearance and drug dissolution were used to calculate total and microscale epithelial absorption of drug delivered with a nasal spray pump. Ranges of suspended particle sizes, drug solubilities, and partition coefficients were evaluated. Considering mometasone furoate as an example, suspended drug particle sizes in the range of 1-5 μm did not affect the total nasal epithelial uptake. However, the microscale absorption of suspended drug particles with low solubilities was affected by particle size and this controlled the extent to which the drug penetrated into the distal nasal regions. The nasal-DAC model was demonstrated to be a useful tool in determining the nasal exposure of spray formulations with different drug particle sizes and solubilities. Furthermore, the model illustrated a new strategy for topical nasal drug delivery in which drug particle size is selected to increase the region of epithelial surface exposure using mucociliary clearance while minimizing the drug dose exiting the nasopharynx.

  8. Recruitment factors which affect the outcome of a seasonal allergic rhinitis trial.

    Sharma, Shilpy; Vasnani, Raj; De Tineo, Marcella; Du, Gaixin; Pinto, Jayant M; Baroody, Fuad M; Naclerio, Robert M

    2011-01-01

    Although intranasal corticosteroids (INSs) are the first-line treatment for seasonal allergic rhinitis (SAR), some patients do not respond adequately, reflecting biological heterogeneity or confounding conditions. The objective of this study was to determine what recruitment factors identify SAR subjects who will be unresponsive to mometasone furoate (MF). We performed a 2-week, double-blind, placebo-controlled, parallel study on 40 subjects with SAR. Each subject underwent a decongestant test using oxymetazoline. Baseline nasal symptoms, nasal peak inspiratory flow (NPIF) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores were recorded. Next, subjects were randomized to either 200 μg of MF or placebo. Symptom diaries and NPIF measurements were completed twice daily. After 2 weeks, subjects repeated the RQLQ and the global assessment of symptoms. There was a significant reduction in symptoms in the MF group compared with placebo (p ≤ 0.05) in patients with baseline total symptom scores of ≥6. Multivariate analysis showed that treatment (MF versus placebo; p = 0.049) and amount of decongestion (percent change in NPIF after oxymetazoline; p = 0.008) predicted the improvement in total nasal symptoms. In clinical trials, SAR subjects must report multiple symptoms to be responsive to treatment with INSs. Our results also support the use of the decongestant test for choice of appropriate study volunteers, both to ensure participation of potentially responsive subjects and to eliminate those with confounding issues.

  9. Computational fluid dynamics: a suitable assessment tool for demonstrating the antiobstructive effect of drugs in the therapy of allergic rhinitis.

    Achilles, N; Pasch, N; Lintermann, A; Schröder, W; Mösges, R

    2013-02-01

    This systematic review aims first to summarize the previous areas of application of computational fluid dynamics (CFD) and then to demonstrate that CFD is also a suitable instrument for generating three-dimensional images that depict drug effects on nasal mucosa. Special emphasis is placed on the three-dimensional visualization of the antiobstructive effect of nasal steroids and antihistamines in the treatment of allergic rhinitis. In the beginning, CFD technology was only used to demonstrate physiological and pathophysiological airflow conditions in the nose and to aid in preoperative planning and postoperative monitoring of surgical outcome in the field of rhinosurgery. The first studies using CFD examined nasal respiratory physiology, important functions of the nose, such as conditioning and warming of inspired air, and the influence of pathophysiological changes on nasal breathing. Also, postoperative outcome of surgical procedures could be "predicted" using the nasal airflow model. Later studies focused on the three-dimensional visualization of the effect of nasal sprays in healthy subjects and postoperative patients. A completely new approach, however, was the use of CFD in the area of allergic rhinitis and the treatment of its cardinal symptom of nasal obstruction. In two clinical trials, a suitable patient with a positive history of allergic rhinitis was enrolled during a symptom-free period after the pollen season. The patient developed typical allergic rhinitis symptoms after provocation with birch pollen. The 3-D visualization showed that the antiallergic treatment successfully counteracted the effects of nasal allergen provocation on nasal airflow. These observations were attributed to the antiobstructive effect of a nasal steroid (mometasone furoate) and a systemic antihistamine (levocetirizine), respectively. CFD therefore constitutes a non-invasive, precise, reliable and objective examination procedure for generating three-dimensional images that

  10. Effect of Direct-to-Consumer Advertising on Asthma Medication Sales and Healthcare Use

    Daubresse, Matthew; Hutfless, Susan; Kim, Yoonsang; Kornfield, Rachel; Qato, Dima M.; Huang, Jidong; Miller, Kay; Emery, Sherry L.

    2015-01-01

    Rationale: The United States is one of only two countries that permit direct-to-consumer advertising (DTCA) of prescription drugs, and many questions remain regarding its effects. Objectives: To quantify the association between asthma-related DTCA, pharmacy sales, and healthcare use. Methods: This was an ecological study from 2005 through 2009 using linked data from Nielsen (DTCA television ratings), the IMS Health National Prescription Audit (pharmacy sales), and the MarketScan Commercial Claims data (healthcare use) for 75 designated market areas in the United States. We used multilevel Poisson regression to model the relationship between DTCA and rates of prescriptions and use within and across designated market areas. Main outcome measures include (1) volume of total, new, and refilled prescriptions for advertised products based on pharmacy sales; (2) prescription claims for asthma medications; and asthma-related (3) emergency department use, (4) hospitalizations, and (5) outpatient encounters among the commercially insured. Measurements and Main Results: Four Food and Drug Administration–approved asthma medicines were advertised during the period examined: (1) fluticasone/salmeterol (Advair), (2) mometasone furoate (Asmanex), (3) montelukast (Singulair), and (4) budesonide/formoterol (Symbicort). After adjustment, each additional televised advertisement was associated with 2% (incident rate ratio, 1.02; 95% confidence interval, 1.01–1.03) higher pharmacy sales rate from 2005 through 2009, although this effect varied across the three consistently advertised therapies examined. Among the commercially insured, DTCA was positively and significantly associated with emergency room visits related to asthma (incident rate ratio, 1.02; 95% confidence interval, 1.01–1.04), but there was no relationship with hospitalizations or outpatient encounters. Conclusions: Among this population, DTCA was associated with higher prescription sales and asthma-related emergency

  11. SEZARY SYNDROME MIMICKING GENERALIZED PSORIASIS VULGARIS

    Eko Rianova Lynoora

    2016-09-01

    Full Text Available Sezary syndrome is the leukemic variant of cutaneous T cell lymphoma. This disease is characterized by some reddish patches or plaques all over the skin which extends to the whole body into erythroderma, lymphadenopathy. It is also indicated by the presence of atypical lymphocytes called Sezary cells. This case report is aimed to know clinical manifestation, examination and management of Sezary syndrome which clinically resembles generalized psoriasis. A 60 years old man came with scaly reddish brown plaques almost all over his body. It was accompanied by lymphadenopathy on the supraclavicular lymph node right and left as well as intense itchy. Other clinical features were alopecia, palmoplantar hyperkeratosis, onychodysthropy, facies leonine without anesthesia on the lesion and enlargement of peripheral nerve. From a laboratory test, an increase in the number of leukocytes and, Sezary cells were found in peripheral blood smear examination; while the histopathology showed focal athrophy and acanthosis of the epidermis and dense infiltration of lymphocytes in the dermo-epidermal junction and superficial dermis. Patient received 3 x 5 mg (1 cycle of methotrexate (MTX with 0,1% cream mometasone furoate and 3x1 tablet of CTM for adjunctive therapy. Methotrexate was discontinued because there was a disturbance in liver function and deterioration of patient’s condition. After 25 days of treatment, the patient got sepsis and then passed away. Early onset of Sezary syndrome in this case is difficult to know because the clinical manifestation is similar with psoriasis vulgaris. Supporting examination such as laboratory test, blood smears and histopathology examination could help the diagnosis. The presence of lymphadenopathy, and atypical lymphocytes in the peripheral blood and the extensive skin involvement reflect the poor prognosis. The most common cause of death was sepsis.

  12. Effect of Direct-to-Consumer Advertising on Asthma Medication Sales and Healthcare Use.

    Daubresse, Matthew; Hutfless, Susan; Kim, Yoonsang; Kornfield, Rachel; Qato, Dima M; Huang, Jidong; Miller, Kay; Emery, Sherry L; Alexander, G Caleb

    2015-07-01

    The United States is one of only two countries that permit direct-to-consumer advertising (DTCA) of prescription drugs, and many questions remain regarding its effects. To quantify the association between asthma-related DTCA, pharmacy sales, and healthcare use. This was an ecological study from 2005 through 2009 using linked data from Nielsen (DTCA television ratings), the IMS Health National Prescription Audit (pharmacy sales), and the MarketScan Commercial Claims data (healthcare use) for 75 designated market areas in the United States. We used multilevel Poisson regression to model the relationship between DTCA and rates of prescriptions and use within and across designated market areas. Main outcome measures include (1) volume of total, new, and refilled prescriptions for advertised products based on pharmacy sales; (2) prescription claims for asthma medications; and asthma-related (3) emergency department use, (4) hospitalizations, and (5) outpatient encounters among the commercially insured. Four Food and Drug Administration-approved asthma medicines were advertised during the period examined: (1) fluticasone/salmeterol (Advair), (2) mometasone furoate (Asmanex), (3) montelukast (Singulair), and (4) budesonide/formoterol (Symbicort). After adjustment, each additional televised advertisement was associated with 2% (incident rate ratio, 1.02; 95% confidence interval, 1.01-1.03) higher pharmacy sales rate from 2005 through 2009, although this effect varied across the three consistently advertised therapies examined. Among the commercially insured, DTCA was positively and significantly associated with emergency room visits related to asthma (incident rate ratio, 1.02; 95% confidence interval, 1.01-1.04), but there was no relationship with hospitalizations or outpatient encounters. Among this population, DTCA was associated with higher prescription sales and asthma-related emergency department use.

  13. Deposition of intranasal glucocorticoids--preliminary study.

    Rapiejko, Piotr; Sosnowski, Tomasz R; Sova, Jarosław; Jurkiewicz, Dariusz

    2015-01-01

    Intranasal glucocorticoids are the treatment of choice in the therapy of rhinitis. The differences in efficiency of particular medications proven by therapeutic index may result from differences in composition of particular formulations as well as from diverse deposition in nasal cavities. Intranasal formulations of glucocorticoids differ in volume of a single dose in addition to variety in density, viscosity and dispenser nozzle structure. The aim of this report was to analyze the deposition of most often used intranasal glucocorticoids in the nasal cavity and assessment of the usefulness of a nose model from a 3D printer reflecting anatomical features of a concrete patient. Three newest and most often used in Poland intranasal glucocorticoids were chosen to analysis; mometasone furoate (MF), fluticasone propionate (FP) and fluticasone furoate (FF). Droplet size distribution obtained from the tested formulations was determined by use of a laser aerosol spectrometer Spraytec (Malvern Instruments, UK). The model of the nasal cavity was obtained using a 3D printer. The printout was based upon a tridimensional reconstruction of nasal cavity created on the basis of digital processing of computed tomography of paranasal sinuses. The deposition of examined medications was established by a method of visualization combined with image analysis using commercial substance which colored itself intensively under the influence of water being the dominant ingredient of all tested preparations. On the basis of obtained results regions of dominating deposition of droplets of intranasal medication on the wall and septum of the nasal cavity were compared. Droplet size of aerosol of tested intranasal medications typically lies within the range of 25-150 µm. All tested medications deposited mainly on the anterior part of inferior turbinate. FP preparation deposited also on the anterior part of the middle nasal turbinate, marginally embracing a fragment of the central part of this

  14. Patient perspectives on fluticasone–vilanterol versus other corticosteroid combination products for the treatment of asthma

    Bollmeier SG

    2016-05-01

    Full Text Available Suzanne G Bollmeier, Theresa R Prosser St Louis College of Pharmacy, St Louis, MO, USA Objective: Fluticasone furoate (FF, an inhaled corticosteroid (ICS, and vilanterol (VI, a long-acting beta2 receptor agonist (LABA, is a new combination used in an Ellipta® device. This article compares FF–VI to other ICS–LABA combinations available, particularly emphasizing product selection from the patient perspective. Data sources: A PubMED and EMBASE search completed in October 2015 identified trials using the MeSH terms “fluticasone”, “vilanterol”, and “asthma”. Additional information was gathered from references cited in the identified publications, the manufacturer, package insert, and ClinicalTrials.gov registry. Study selection/data extraction: Preference was given to randomized controlled clinical trials. Animal trials, trials for COPD, and non-English sources were excluded. Data synthesis: Seven efficacy trials of FF–VI in asthma were identified. Only one (24 weeks trial compared FF–VI to another ICS–LABA combination (fluticasone propionate–salmeterol. Primary outcomes (usually lung function and secondary outcomes (eg, quality of life and symptom scores were comparable. In three FF–VI safety trials, the type and frequency of common adverse reactions (ie, thrush and dysphonia were similar to those in clinical trials. Over 90% of subjects rated the Ellipta® device as “easy to use” and demonstrated correct device technique initially and at 4 weeks. Conclusion: Individuals may have drug- and device-specific preferences that should be incorporated into therapeutic decision making. Limited data indicate that clinical and patient-oriented efficacy/safety outcomes of FF–VI are likely comparable to other available combinations for adults with asthma. Patient-friendly features include once-daily dosing, flexibility of dose timing, and design/ease of the use of the device. Additional larger and long-term comparative

  15. Simultaneous Marine Observations

    National Oceanic and Atmospheric Administration, Department of Commerce — Observations from Naval vessels, primarily American, taken once daily at Greenwich Noon time. Forms are monthly and were captured from records held at the National...

  16. Comparison of the efficacy and safety of budesonide turbuhaler ...

    Comparison of the efficacy and safety of budesonide turbuhaler administered once daily with twice the dose of beclomethasone dipropionate using pressurised metered dose inhaler in patients with mild to moderate asthma.

  17. histomorphometric and histopathological studies on the effectof ...

    Dr Olaleye

    Histomorphometric and histopathological evaluations of the effects of fresh leaf extract of Calotropis procera on the reproductive organs of male wistar rats given 20mg\\gm body weight of the extract once daily, ..... Antifertility Drugs of India.

  18. Evaluation of Orally Delivered ST-246 as Postexposure Prophylactic and Antiviral Therapeutic in an Aerosolized Rabbitpox Rabbit Model

    Nalca, Aysegul; Hatkin, Josh M; Garza, Nicole L; Nichols, Donald K; Norris, Sarah W; Hruby, Dennis E; Jordan, Robert

    2008-01-01

    ...) to treat smallpox or monkeypox infection. In this study, we showed that administration of the antiviral compound ST-246 to rabbits by oral gavage, once daily for 14 days beginning 1h postexposure (p.e.), resulted in 100...

  19. Tetomilast.

    O'Mahony, Seamus

    2012-02-03

    Otsuka is developing a once-daily oral formulation of the phosphodiesterase-4 inhibitor tetomilast for the potential treatment of ulcerative colitis (phase III) and chronic obstructive pulmonary disease (phase II).

  20. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study

    Cheng, Gregory; Saleh, Mansoor N; Marcher, Claus

    2011-01-01

    Eltrombopag is an oral thrombopoietin receptor agonist for the treatment of thrombocytopenia. We aimed to compare the response to once daily eltrombopag versus placebo in patients with chronic immune thrombocytopenia during a 6-month period....

  1. Bicalutamide 150 mg plus standard care vs standard care alone for early prostate cancer

    McLeod, David G; Iversen, Peter; See, William A

    2006-01-01

    To evaluate, in the ongoing Early Prostate Cancer (EPC) trial programme, the efficacy and tolerability of bicalutamide 150 mg once daily in addition to standard care for localized or locally advanced, nonmetastatic prostate cancer....

  2. Efficacy and Tolerability of Tamsulosin 0.4 mg in Patients with Symptomatic Benign Prostatic Hyperplasia

    Chung, Jae-Wook; Choi, Seock Hwan; Kim, Bum Soo; Kim, Tae-Hwan; Yoo, Eun Sang; Kim, Chun Il; Lee, Kyung Seop; Kwon, Tae Gyun

    2011-01-01

    Purpose To evaluate the efficacy and tolerability of tamsulosin 0.4 mg once daily in Korean patients with symptomatic benign prostatic hyperplasia (BPH) and investigate whether tamsulosin 0.4 mg can improve symptoms in patients with refractory lower urinary tract symptoms (LUTS) who were previously receiving tamsulosin 0.2 mg once daily. Materials and Methods A total of 116 patients from 3 urology centers participated. All study subjects entered a nonblind phase consisting of 8 weeks of tamsu...

  3. Weather/temperature-sensitive vasomotor rhinitis may be refractory to intranasal corticosteroid treatment.

    Jacobs, Robert; Lieberman, Philip; Kent, Edward; Silvey, MaryJane; Locantore, Nicholas; Philpot, Edward E

    2009-01-01

    Vasomotor rhinitis (VMR) is a common but poorly understood disorder of which there are two major subgroups: VMR(w/t), triggered by weather/temperature and VMR(ir), triggered by airborne irritants. No specific biological pathways or specific treatments for VMR(w/t) or VMR(ir) have been identified. However, intranasal corticosteroids (INSs) are effective in treating many forms of nonallergic rhinitis that include these conditions. A recently introduced INS with established efficacy in allergic rhinitis and enhanced affinity, fluticasone furoate, may possess the potency and safety profile required to treat chronic VMR(w/t). Two replicate studies (FFR30006 and FFR30007) were conducted in six countries to evaluate the efficacy and safety of fluticasone furoate nasal spray in subjects with VMR(w/t). After a 7- to 14-day screening period, subjects (n = 699) with symptomatic VMR(w/t) received fluticasone furoate, 110 mug q.d. or placebo for 4 weeks in these two randomized, double-blind, parallel-group studies. Subjects rated their nasal symptoms (congestion, rhinorrhea, and postnasal drip) twice daily on a 4-point categorical scale and evaluated their overall response to treatment at study end. Fluticasone furoate did not significantly improve daily reflective total nasal symptom scores, the primary end point, versus placebo (p = 0.259) and there was no improvement in any other measure of efficacy. The active treatment was well tolerated. Fluticasone furoate was not effective in treating subjects with a newly defined condition, weather-sensitive VMR. These unexpected results suggest that VMR(w/t) is a distinct subgroup of VMR that is refractory to treatment with INSs. Additional study of other treatments for VMR(w/t) (including INSs) is warranted.

  4. Once- versus twice-daily aspirin treatment in patients with essential thrombocytosis

    Larsen, Mads Lamm; Pedersen, Oliver Heidmann; Hvas, Anne-Mette

    2018-01-01

    Insufficient platelet inhibition has been reported in up to 40% of aspirin-treated patients, including patients with essential thrombocytosis. To maintain sufficient platelet inhibition, a shorter dosing interval with aspirin has been suggested. We aimed to investigate the antiplatelet effect...... of low-dose aspirin given twice-daily compared to standard once-daily dosing in patients with essential thrombocytosis. We included 22 patients, who were treated for 7 days with standard once-daily aspirin (75 mg once-daily) followed by 7 days treatment of twice-daily aspirin (37.5 mg twice......-daily). The two regimens were separated by 14 days aspirin washout. Blood samples were obtained 1h and 24h/12h after the last pill intake in each regimen. The effect of aspirin was evaluated by: (1) platelet aggregation measured by whole blood impedance aggregometry (Multiplate® Analyser) using arachidonic acid...

  5. Patient considerations in the treatment of COPD: focus on the new combination inhaler umeclidinium/vilanterol

    Albertson TE

    2015-02-01

    Full Text Available Timothy E Albertson,1–3 Richart Harper,1,2 Susan Murin,1,2 Christian Sandrock1 1Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, School of Medicine, University of California, Davis, Sacramento, CA, USA; 2Department of Medicine, Veterans Administration Northern California Health Care System, Mather, CA, USA; 3Department of Emergency Medicine, School of Medicine, University of California, Davis, Sacramento, CA, USA Abstract: Medication adherence among patients with chronic diseases, such as COPD, may be suboptimal, and many factors contribute to this poor adherence. One major factor is the frequency of medication dosing. Once-daily dosing has been shown to be an important variable in medication adherence in chronic diseases, such as COPD. New inhalers that only require once-daily dosing are becoming more widely available. Combination once-daily inhalers that combine any two of the following three agents are now available: 1 a long-acting muscarinic antagonist; 2 a long acting beta2 agonist; and 3 an inhaled corticosteroid. A new once-daily inhaler with both a long-acting muscarinic antagonist, umeclidinium bromide, and a long acting beta2 agonist, vilanterol trifenatate, is now available worldwide for COPD treatment. It provides COPD patients convenience, efficacy, and a very favorable adverse-effects profile. Additional once-daily combination inhalers are available or will soon be available for COPD patients worldwide. The use of once-daily combination inhalers will likely become the standard maintenance management approach in the treatment of COPD because they improve medication adherence. Keywords: medication adherence, long-acting beta2 agonist, long-acting muscarinic antagonist, inhaled corticosteroid, chronic obstructive pulmonary disease

  6. Comparative efficacy of indacaterol in chronic obstructive pulmonary disease

    Ribeiro M

    2012-03-01

    Full Text Available Marcos Ribeiro, Kenneth R ChapmanAsthma and Airway Centre, University Health Network, Toronto Western Hospital, University of Toronto, Toronto, ON, CanadaAbstract: Long-acting bronchodilators have been shown to improve multiple clinical outcomes in chronic obstructive pulmonary disease (COPD including lung function, symptoms, dyspnea, quality of life, and exacerbations. Indacaterol is a novel, inhaled, long-acting β2-agonist providing 24-hour bronchodilation with once-daily dosing. It is currently approved for the maintenance treatment of COPD to be administered as 150 or 300 µg once-daily doses as licensed in many countries and 75 µg as licensed in the US by means of a single-dose dry powder inhaler. The data from clinical development support a favorable safety and tolerability profile within the β2-agonist drug class, with no relevant issues identified. Current evidence indicates that indacaterol is suitable for use as first-line monotherapy in COPD patients with moderate disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage II and beyond that do not require an inhaled corticosteroid (ICS as per GOLD guidelines, or in combination with an ICS in severe or very severe patients with repeated exacerbations. Data from trials with the novel once-daily β2-agonist, indacaterol, indicate superior bronchodilation and clinical efficacy over twice-daily long-acting β2-agonists and at least equipotent bronchodilation as once-daily tiotropium. Bronchodilators are central in the symptomatic management of COPD. It is likely that once-daily dosing of a bronchodilator would be a significant convenience and probably a compliance-enhancing advantage, leading to improved overall clinical outcomes in patients with COPD.Keywords: indacaterol, onset of action, chronic obstructive pulmonary disease, bronchodilators, once-daily, long-acting β2-agonists

  7. Cost-effectiveness of exenatide twice daily vs insulin glargine as add-on therapy to oral antidiabetic agents in patients with type 2 diabetes in China.

    Gu, Shuyan; Wang, Xiaoyong; Qiao, Qing; Gao, Weiguo; Wang, Jian; Dong, Hengjin

    2017-12-01

    To estimate the long-term cost-effectiveness of exenatide twice daily vs insulin glargine once daily as add-on therapy to oral antidiabetic agents (OADs) for Chinese patients with type 2 diabetes (T2DM). The Cardiff Diabetes Model was used to simulate disease progression and estimate the long-term effects of exenatide twice daily vs insulin glargine once daily. Patient profiles and treatment effects required for the model were obtained from literature reviews (English and Chinese databases) and from a meta-analysis of 8 randomized controlled trials comparing exenatide twice daily with insulin glargine once daily add-on to OADs for T2DM in China. Medical expenditure data were collected from 639 patients with T2DM (aged ≥18 years) with and without complications incurred between January 1, 2014 and December 31, 2015 from claims databases in Shandong, China. Costs (2014 Chinese Yuan [¥]) and benefits were estimated, from the payers' perspective, over 40 years at a discount rate of 3%. A series of sensitivity analyses were performed. Patients on exenatide twice daily + OAD had a lower predicted incidence of most cardiovascular and hypoglycaemic events and lower total costs compared with those on insulin glargine once daily + OAD. A greater number of quality-adjusted life years (QALYs; 1.94) at a cost saving of ¥117 706 gained was associated with exenatide twice daily vs insulin glargine once daily. (i.e. cost saving of ¥60 764/QALY) per patient. In Chinese patients with T2DM inadequately controlled by OADs, exenatide twice daily is a cost-effective add-on therapy alternative to insulin glargine once daily, and may address the problem of an excess of medical needs resulting from weight gain and hypoglycaemia in T2DM treatment. © 2017 John Wiley & Sons Ltd.

  8. Efficacy of controlled-release isosorbide-5-mononitrate as adjunctive treatment to beta-blocking agents in patients with stable angina pectoris

    Svendsen, Jesper Hastrup; Aldershvile, J; Abildgaard, U

    1989-01-01

    to a beta blocker. In bicycle ergometer exercise tests performed 4 h after study drug intake, total exercise time and time until 1-mm ST-depression increased significantly during both regimens as compared with placebo (p less than 0.05). However, only the 60-mg once-daily regimen was significantly better...... than placebo with regard to time until angina pectoris. The results indicate that ISMN-CR 60 mg once daily is effective as adjunctive to beta-blocker treatment, and nitrate tolerance appeared to develop during the twice-daily regimen. In 10 of the patients, the effect of additional sublingual...

  9. Olmsted Syndrome

    Sirka C

    1999-01-01

    Full Text Available A 20-year-old Sikh man had palmoplantar keratoderma, flexion deformity of digits, universal alopecia, keratotic plaques at the angles of mouth, gluteal cleft, knees and dorsal aspects of the metacarpophalangeal joints of the hand; features of Olmsted syndrome. He had normal nails, teeth, oral mucosa and normal joint movements. Treatment with acitretin, 25mg/day for three and a half months, followed by 25mg once daily alternating with 50mg once daily for 3 months resulted in significant improvement.

  10. 12500 E heparin and 12500 E of a semisynthetic heparin analogue (SSHA) in preventing thrombosis during radiotherapy of gynaecological carcinomas

    Hilscher, T.M.

    1983-01-01

    The effects of 12500 E calcium heparin given once daily were contrasted with those seen under daily treatment with 12500 E of a semisynthetic heparin analogue (SSHA) and evaluated using iodine-125-labelled fibrinogen. The study included 80 patients, who were randomly assigned to the two treatment groups on a 1:1 basis. The findings revealed here led to the conclusion that both drugs, administered once daily by the subcutaneous route, were effective in preventing the occurrence of thrombosis during radiation treatment of gynaecological tumours. (orig./MG) [de

  11. Author Details

    ... JO, Medical Department, AstraZeneca, P. O. Box 3560, Ikeja, Lagos. Vol 24, No 3 (2005) - Articles Comparison of the efficacy and safety of budesonide turbuhaler administered once daily with twice the dose of beclomethasone dipropionate using pressurised metered dose inhaler in patients with mild to moderate asthma

  12. West African Journal of Medicine - Vol 24, No 3 (2005)

    Comparison of the efficacy and safety of budesonide turbuhaler administered once daily with twice the dose of beclomethasone dipropionate using pressurised metered dose inhaler in patients with mild to moderate asthma · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL ...

  13. Hatchability of chicken eggs as influenced by turning frequency in ...

    An experiment was conducted to determine the influence of turning frequency of chicken eggs on hatchability in hurricane lantern incubator. There were four treatments in which eggs were not turned in treatment one (control), those in treatment two were turned once daily (morning), treatment three turned twice daily ...

  14. Effects of sub acute oral administration of aqueous extract of ...

    The study evaluates the effects of sub acute oral administration (28 days) of aqueous extract of Stereospermum kunthianum stem bark on the body weight and haematological indices of rats. Treatments were administered by oral gavage once daily for a total of 28 days. The first group (control) received distilled water (5 ...

  15. Haemoglobin A(1c) goal attainment in relation to dose in patients with diabetes mellitus taking metformin

    Penning-van Beest, Fernie J. A.; Wolffenbuttel, Bruce H. R.; Herings, Ron M. C.

    2008-01-01

    Background and objective: Conclusions from clinical trials suggest possible therapeutic advantages for once-daily agents over twice-daily agents in the treatment of type 2 diabetes mellitus. This study set out to investigate the relationship between metformin dosing frequency and glycosylated

  16. CheckMate 025 Randomized Phase 3 Study: Outcomes by Key Baseline Factors and Prior Therapy for Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma

    Escudier, Bernard; Sharma, Padmanee; McDermott, David F

    2017-01-01

    /kg every 2 wk or everolimus 10mg once daily. RESULTS AND LIMITATIONS: The minimum follow-up was 14 mo. Baseline subgroup distributions were balanced between nivolumab and everolimus arms. Nivolumab demonstrated an OS improvement versus everolimus across subgroups, including Memorial Sloan Kettering Cancer...... Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium risk groups; age

  17. A randomized clinical trial comparing the effect of basal insulin and inhaled mealtime insulin on glucose variability and oxidative stress

    Siegelaar, S. E.; Kulik, W.; van Lenthe, H.; Mukherjee, R.; Hoekstra, J. B. L.; DeVries, J. H.

    2009-01-01

    To assess the effect of three times daily mealtime inhaled insulin therapy compared with once daily basal insulin glargine therapy on 72-h glucose profiles, glucose variability and oxidative stress in type 2 diabetes patients. In an inpatient crossover study, 40 subjects with type 2 diabetes were

  18. A comparison of the blood pressure changes of lumiracoxib with those of ibuprofen and naproxen.

    Farkouh, M.E.; Verheugt, F.W.A.; Ruland, S.; Kirshner, H.; Jeger, R.; Gitton, X.; Krammer, G.; Stricker, K.; Sallstig, P.; Mellein, B.; Matchaba, P.; Chesebro, J.H.

    2008-01-01

    The 52-week Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) investigated the gastrointestinal and cardiovascular safety profile of lumiracoxib 400 mg once daily compared with 2 traditional nonsteroidal anti-inflammatory drugs (NSAIDs): ibuprofen 800 mg 3 times daily and

  19. The effect of the circadian rhythm on the clearance of aminoglycosides in ICU patients

    Van Maarseveen, E.; Proost, J.; Neef, C.; Touw, D.

    Aims: Critically ill patients, admitted to an intensive care unit, are at high risk of acquiring a nosocomial infection. Aminoglycosides (AMGs) are frequently used as first line therapy in severe hospital-acquired pneumonia or sepsis. It has been shown that once daily dosing (ODD) can reduce toxic

  20. 21 CFR 520.1330 - Meclofenamic acid granules.

    2010-04-01

    ... milligram per pound of body weight (1 gram per 1,000 pounds) once daily for 5 to 7 days by addition to the daily grain ration. (3) Treatment beyond the initial 5- to 7-day period may be indicated. A maintenance dosage level should be individualized for each animal. (4) This drug should not be administered to horses...

  1. An open-label Optional Titration Trial to Evaluate the Efficacy ...

    An eight-week open-label optional titration trial to evaluate the efficacy, tolerability and safety of Valsartan 80 mg/ & 160 mg once daily was carried out in patients with mild to moderate essential hypertension at the Lagos University Teaching Hospital. There was a significant reduction in both systolic and diastolic blood ...

  2. Pharmacokinetically guided sunitinib dosing: a feasibility study in patients with advanced solid tumours

    Lankheet, N.; Kloth, J.S.; Gadellaa-van Hooijdonk, C.G.M.; Cirkel, G.A.; Mathijssen, R.H.; Lolkema, M.P.; Schellens, J.H.; Voest, E.E.; Sleijfer, S.; Jonge, M.J. de; Haanen, J.B.; Beijnen, J.H.; Huitema, A.D.; Steeghs, N.

    2014-01-01

    Background:Plasma exposure of sunitinib shows large inter-individual variation. Therefore, a pharmacokinetic (PK) study was performed to determine safety and feasibility of sunitinib dosing based on PK levels.Methods:Patients were treated with sunitinib 37.5 mg once daily. At days 15 and 29 of

  3. Mahomoodally Afr J Tradit Complement Altern Med. (2014) 11(6):1-32

    cadewumi

    Nonetheless, further research is needed to investigate the possible active constituents that ... phytochemicals resulting from their therapeutic ability towards diseases like cancer, ... of diseases for instance HIV /AIDS, malaria, diabetes, sickle-cell ..... leaves and Piper betle L. leaves. Drink once daily at night. Respiratory tract.

  4. Short-term effects of liraglutide on kidney function and vasoactive hormones in type 2 diabetes

    Skov, J.; Pedersen, M.; Holst, Jens Juul

    2016-01-01

    AIMS: To investigate the effects of a single dose of 1.2 mg liraglutide, a once-daily glucagon-like peptide-1 (GLP-1) receptor agonist, on key renal parameters in patients with type 2 diabetes. METHODS: The study was a placebo-controlled, double-blind, cross-over in 11 male patients with type 2 d...

  5. 21 CFR 520.928 - Firocoxib tablets.

    2010-04-01

    .... Administer once daily for osteoarthritis. Administer approximately 2 hours before soft-tissue or orthopedic...; and for the control of postoperative pain and inflammation associated with soft-tissue and orthopedic surgery. (3) Limitations. Federal law restricts this drug to use by or on the order of a licensed...

  6. Glycaemic index of selected staple carbohydrate-rich foods ...

    2013-01-28

    Jan 28, 2013 ... of chronic diseases, e.g. diabetes and obesity.1-4 It is defined as the incremental blood ... fasting. GI was determined using a standard method with white bread. Outcome .... was given a lunch voucher once daily during the participation period. ..... using the continuous glucose MiniMed monitor. Diabetes ...

  7. Update of monotherapy trials with the new anti-androgen, Casodex (ICI 176,334). International Casodex Investigators

    Iversen, P

    1994-01-01

    Casodex (ICI 176,334) is a non-steroidal anti-androgen, which has a half-life compatible with once-daily oral dosing. In an open, phase II study on 267 patients given Casodex, 50 mg/day, an overall objective response (i.e. partial regression) was seen in 55.5% of patients (146 of 263) with a furt...

  8. Effect of drought stress on early growth of Adansonia digitata (L.) in ...

    Drought and high temperatures are said to have triggered increased tree mortality and could be linked to the menace of climate change. This research therefore investigated the effect of drought stress on early growth of Adansonia digitata where seedlings were exposed to different watering frequencies (Once daily, after 3, ...

  9. Randomised clinical trial

    Reimer, C; Lødrup, A; Smith, G

    2016-01-01

    of an alginate (Gaviscon Advance, Reckitt Benckiser, Slough, UK) on reflux symptoms in patients with persistent symptoms despite once daily PPI. MethodsThis was a multicentre, randomised, placebo-controlled, 7-day double-blind trial preceded by a 7-day run-in period. Reflux symptoms were assessed using...

  10. Tamsulosin: real life clinical experience in 19,365 patients

    Michel, M. C.; Bressel, H. U.; Mehlburger, L.; Goepel, M.

    1998-01-01

    OBJECTIVE: To compare the efficacy, global tolerability and blood pressure effects of tamsulosin (0.4 mg once daily) in subgroups of patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO). METHODS: Data from two open-label, observational studies (Study I:

  11. Comparative evaluation of fluoride release from PRG-composites and compomer on application of topical fluoride: An in-vitro study

    Dhull K

    2009-03-01

    Full Text Available Aims and Objective: To determine the fluoride release from Giomer and Compomer, using different topical fluoride regimes, and to compare the amount of fluoride release from giomer with that of compomer. Materials and Method: Forty-eight specimens of each giomer and compomer were divided into four treatment groups, namely, control group, fluoridated dentifrice (500 ppm once daily group, fluoridated dentifrice (500 ppm twice daily group, fluoridated dentifrice (500 ppm once daily + fluoridated mouthwash (225 ppm group. Each specimen was suspended in demineralizing solution for six hours and remineralizing solution for 18 hours. Fluoride release was measured in both the demineralizing solution and remineralizing solution daily for seven days. Total daily fluoride release for each specimen was calculated by adding the amount released in the demineralizing solution to that released in remineralizing solution. Results and Conclusion: The fluoride release (ppm was found to be more in Giomer when compared to Compomer. The fluoride released from Giomer and Compomer was significantly greater in the acidic demineralizing solution than in the neutral remineralizing solution. It was found that increasing fluoride exposure significantly increased fluoride release from the giomer and compomer. It was found that the fluoride release from the subgroups of giomer and compomer was in the following order: fluoridated dentifrice twice daily > fluoridated dentifrice once daily + fluoridated mouthwash > fluoridated dentifrice once daily > control group. It was found that the giomer showed a greater fluoride uptake than the compomer.

  12. Probiotics to prevent necrotising enterocolitis in very preterm infants

    Lambæk, Irina Dobychina; Fonnest, Gert; Gormsen, Magdalena

    2016-01-01

    (bifidobacillus and lactobacillus) once daily by nasogastric tube from the third day of life. The main outcome: NEC grades 2 and 3 were assessed in a blinded fashion from a clinical abstract and available X-rays. RESULTS: A total of 381 infants treated before the change of policy were compared with 333 infants...

  13. Efficacy and safety of rilpivirine (TMC278) versus efavirenz at 48 weeks in treatment-naive HIV-1-infected patients: pooled results from the phase 3 double-blind randomized ECHO and THRIVE Trials.

    Cohen, Calvin J; Molina, Jean-Michel; Cahn, Pedro; Clotet, Bonaventura; Fourie, Jan; Grinsztejn, Beatriz; Wu, Hao; Johnson, Margaret A; Saag, Michael; Supparatpinyo, Khuanchai; Crauwels, Herta; Lefebvre, Eric; Rimsky, Laurence T; Vanveggel, Simon; Williams, Peter; Boven, Katia

    2012-05-01

    Pooled analysis of phase 3, double-blind, double-dummy ECHO and THRIVE trials comparing rilpivirine (TMC278) and efavirenz. Treatment-naive HIV-1-infected adults were randomized 1:1 to rilpivirine 25 mg once daily or efavirenz 600 mg once daily, with background tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) (ECHO) or TDF/FTC, zidovudine/lamivudine, or abacavir/lamivudine (THRIVE). The primary endpoint was confirmed response [viral load effects on virologic failure were more apparent with rilpivirine. CD4 cell count increased over time in both groups. Rilpivirine compared with efavirenz gave smaller incidences of adverse events leading to discontinuation (3% vs. 8%, respectively), treatment-related grade 2-4 adverse events (16% vs. 31%), rash (3% vs. 14%), dizziness (8% vs. 26%), abnormal dreams/nightmares (8% vs. 13%), and grade 2-4 lipid abnormalities. At week 48, rilpivirine 25 mg once daily and efavirenz 600 mg once daily had comparable response rates. Rilpivirine had more virologic failures and improved tolerability versus efavirenz.

  14. Safety and efficacy of an 8-week regimen of grazoprevir plus ruzasvir plus uprifosbuvir compared with grazoprevir plus elbasvir plus uprifosbuvir in participants without cirrhosis infected with hepatitis C virus genotypes 1, 2, or 3 (C-CREST-1 and C-CREST-2, part A)

    Gane, Edward J; Pianko, Stephen; Roberts, Stuart K

    2017-01-01

    BACKGROUND: New hepatitis C virus (HCV) therapies with pan-genotypic efficacy are needed. The goals of part A of C-CREST-1 and C-CREST-2 were to compare the efficacies of two doses (300 mg or 450 mg once daily) of uprifosbuvir (MK-3682; NS5B inhibitor) in an 8-week regimen combined with grazoprev...

  15. Effects of Zingiber officinale extract on antioxidation and lipid ...

    Yomi

    2012-02-07

    Feb 7, 2012 ... 200, 400, 800 or 1600 mg/kg body weight (B.W.) of ZOE (oral gavage) p.o. once daily for five days. Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities increased, and malondialdehyde (MDA) contents decreased along with an increase in the ZOE dose of up to 800.

  16. Oral fingolimod (FTY720) in multiple sclerosis: two-year results of a phase II extension study

    O'Connor, P; Comi, G; Montalban, X

    2009-01-01

    OBJECTIVE: To report the results of a 24-month extension of a phase II trial assessing the efficacy, safety, and tolerability of the once-daily oral sphingosine-1-phosphate receptor modulator, fingolimod (FTY720), in relapsing multiple sclerosis (MS). METHODS: In the randomized, double-blind, pla...

  17. Combinations of long acting β2 agonists to tiotropium: A randomized, double-blind, placebo-controlled, active-drug controlled, parallel design academic clinical trial in moderate COPD male patients

    Mohammed Imran

    2015-01-01

    Conclusions: Study shows that tiotropium alone once a day is the evidence based and rationale pharmacotherapy in moderate COPD. There is no advantage or statistical significance of adding long acting β2 agonists (LABA such as formoterol to tiotropium either for 12 h (once daily or 24 h (twice daily.

  18. Recommendations for constructing forest stream crossings to control soil losses

    Pamela J. Edwards; Jingxin Wang; Joshua T. Stedman

    2009-01-01

    Stream water samples were collected once daily and throughout storms from a small forested watershed in north central West Virginia for approximately 8 years. The turbidities of the samples were measured to determine how water quality changed in response to the construction of three associated stream crossings. The influence of the...

  19. Ciprofibrate versus gemfibrozil in the treatment of primary hyperlipidaemia

    Knipscheer, H. C.; de Valois, J. C.; van den Ende, B.; ten Cate, J. Wouter; Kastelein, J. J.

    1996-01-01

    The efficacy and short-term safety of ciprofibrate and gemfibrozil were compared in a 12-week, double-blind, randomised study. One-hundred-and-ten primary, type II hyperlipidaemic patients were randomised to receive either ciprofibrate, 100 mg/day once daily, or gemfibrozil, 1200 mg/day twice daily.

  20. Astragaloside IV liposomes ameliorates adriamycin-induced ...

    Methods: The rats were given a single tail intravenous injection of adriamycin (6 mg/kg) within 1 week, and then divided into four groups including normal, model, benazepril and astragaloside IV liposomes group. They were all orally administered dosage of benazepril and astragaloside IV liposomes once daily for 8 weeks.

  1. in vivo antitrypanosomal evaluation of some medicinal plant extracts

    Administrator

    administered once daily for 7 days in an established infection of 5 x 106 parasitaemia before ... control, as development of vaccines against AAT is still in progress. ... Plant preparation and extracts: The plants part were air-dried in the laboratory at room .... in some African countries, frequently used against malaria and fever ...

  2. Dose-remission of pulsating electromagnetic fields as augmentation in therapy-resistant depression

    Straasø, Birgit; Lauritzen, Lise; Lunde, Marianne

    2014-01-01

    OBJECTIVE: To evaluate to what extent a twice daily dose of Transcranial Pulsating ElectroMagnetic Fields (T-PEMF) was superior to once daily in patients with treatment-resistant depression as to obtaining symptom remission after 8 weeks of augmentation therapy. METHODS: A self-treatment set...

  3. Human mass balance study and metabolite profiling of 14C-niraparib, a novel poly(ADP-Ribose) polymerase (PARP)-1 and PARP-2 inhibitor, in patients with advanced cancer

    van Andel, Lotte; Zhang, Z; Lu, S.; Kansra, V; Agarwal, S.; Hughes, L.; Tibben, M.; Gebretensae, A.; Lucas, L.; Hillebrand, Michel J X; Rosing, H.; Schellens, J H M|info:eu-repo/dai/nl/073926272; Beijnen, J H|info:eu-repo/dai/nl/071919570

    2017-01-01

    Niraparib is an investigational oral, once daily, selective poly(ADP-Ribose) polymerase (PARP)-1 and PARP-2 inhibitor. In the pivotal Phase 3 NOVA/ENGOT/OV16 study, niraparib met its primary endpoint of improving progression-free survival (PFS) for adult patients with recurrent, platinum sensitive,

  4. Reducing supplementation frequency for Nellore beef steers grazing tropical pastures

    Roberta Carrilho Canesin

    2014-04-01

    Full Text Available Reduced supplementation frequency is a broadly applied management practice. Ruminants consuming low quality forages/pastures, supplemented less than once daily are able to maintain body weight gain (BWG, efficiency of use of dry matter, nitrogen and other nutrients, as compared with animals supplemented once daily. We evaluated the feeding behavior, dry matter intake (DMI, dry matter and organic matter digestibility (DMD and OMD, BWG, Longissimus muscle area and backfat depth of Nellore steers raised on Brachiaria brizantha cv. Marandu pastures during the dry season, with different supplementation patterns. Thirty six animals (338 ± 40.7 kg were distributed over nine paddocks according to a completely randomized design. Treatments were based on supplementation frequency: once daily (OD, once daily except Saturdays and Sundays (SS, or on alternate days (AD, at 1.0 %, 1.4 % and 2.0 % BW, respectively. Average total DMI accounted for 1.6 % BW day-1, with no effect of supplementation frequency. Supplementation frequency had no effect on BWG or grazing time during the day. There was no difference in Longissimus muscle area animals supplemented daily, SS and AD. The backfat depth was thinner in animals supplemented AD, but even in this case, it was within the standards considered satisfactory for a finishing steer. Reducing supplementation frequency seems a good option to lower labor costs without affecting feed efficiency or carcass quality in beef cattle grazing tropical pastures.

  5. Transdermal administration of radiolabelled [14C]rotigotine by a patch formulation: A mass balance trial

    Cawello, W.; Wolff, H.M.; Meuling, W.J.A.; Horstmann, R.; Braun, M.

    2007-01-01

    Background and objective: The dopamine agonist rotigotine has been formulated in a silicone-based transdermal system for once-daily administration. The objective of the present study was to characterise the mass balance of rotigotine in humans after administration of a single transdermal patch

  6. The translation and validation of Chinese overactive bladder symptom score for assessing overactive bladder syndrome and response to solifenacin treatment

    Eric Chieh-Lung Chou

    2014-08-01

    Conclusion: The Chinese OABSS has been validated as a reliable instrument for assessing OAB. Solifenacin 5 mg once daily improved urgency and other symptoms of OAB including frequency, urge incontinence, OABSS and International Prostatic Symptom Score. The adverse effects were acceptable and became less significant with time in the three months of treatment.

  7. 21 CFR 520.2605 - Trimeprazine tartrate and prednisolone capsules.

    2010-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2605...) Amount. Administer either capsule orally once daily to dogs as follows: Animal weight (pounds) Number of... dermatitis (allergic, parasitic, pustular, and nonspecific). It is also used in dogs as adjunctive therapy in...

  8. Insulin degludec in type 1 diabetes: a randomized controlled trial of a new-generation ultra-long-acting insulin compared with insulin glargine

    Birkeland, Kåre I.; Home, Philip D.; Wendisch, Ulrich; Ratner, Robert E.; Johansen, Thue; Endahl, Lars A.; Lyby, Karsten; Jendle, Johan H.; Roberts, Anthony P.; DeVries, J. Hans; Meneghini, Luigi F.

    2011-01-01

    Insulin degludec (IDeg) is a basal insulin that forms soluble multihexamers after subcutaneous injection, resulting in an ultra-long action profile. We assessed the efficacy and safety of IDeg formulations administered once daily in combination with mealtime insulin aspart in people with type 1

  9. Long-acting methylphenidate-OROS in youths with attention-deficit hyperactivity disorder suboptimally controlled with immediate-release methylphenidate : a study of cost effectiveness in The Netherlands

    Faber, Adrianne; van Agthoven, Michel; Kalverdijk, Luuk J; Tobi, Hiltje; de Jong-van den Berg, Lolkje T W; Annemans, Lieven; Postma, Maarten J

    2008-01-01

    Background: Attention-deficit hyperactivity disorder (ADHD) is the most common mental health disorder in youths. Stimulants are the drugs of first choice in the treatment of ADHD. It has been suggested that full costs associated with the treatment of ADHD may be reduced by once-daily administration

  10. Long-Acting Methylphenidate-OROS in Youths with Attention-Deficit Hyperactivity Disorder Suboptimally Controlled with Immediate-Release Methylphenidate. A study of cost effectiveness in The Netherlands.

    Faber, A.; Agthoven, van M.; Kalverdijk, L.J.; Tobi, H.; Jong-van den Berg, de L.T.W.; Annemans, L.; Postma, M.J.

    2008-01-01

    BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is the most common mental health disorder in youths. Stimulants are the drugs of first choice in the treatment of ADHD. It has been suggested that full costs associated with the treatment of ADHD may be reduced by once-daily administration

  11. Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT-288, in healthy young adults and elderly volunteers.

    Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Zhang, Jun; Dutta, Sandeep

    2013-05-01

    The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H3 receptor antagonist, in healthy young adults and elderly subjects following single and multiple dosing in a phase 1 setting. Single doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open label, randomized, crossover design. ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single doses up to 40 mg and multiple doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse events were hot flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 h across dose groups. Steady state was achieved by day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to phase 2 evaluation in Alzheimer's patients. © 2012 Abbott Laboratories. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  12. The effect of a corticosteroid cream and a barrier-strengthening moisturizer in hand eczema. A double-blind, randomized, prospective, parallel group clinical trial.

    Lodén, M; Wirén, K; Smerud, K T; Meland, N; Hønnås, H; Mørk, G; Lützow-Holm, C; Funk, J; Meding, B

    2012-05-01

    Hand eczema is a common and persistent disease with a relapsing course. Clinical data suggest that once daily treatment with corticosteroids is just as effective as twice daily treatment. The aim of this study was to compare once and twice daily applications of a strong corticosteroid cream in addition to maintenance therapy with a moisturizer in patients with a recent relapse of hand eczema. The study was a parallel, double-blind, randomized, clinical trial on 44 patients. Twice daily application of a strong corticosteroid cream (betamethasone valerate 0.1%) was compared with once daily application, where a urea-containing moisturizer was substituted for the corticosteroid cream in the morning. The investigator scored the presence of eczema and the patients judged the health-related quality of life (HRQoL) using the Dermatology Life Quality Index (DLQI), which measures how much the patient's skin problem has affected his/her life over the past week. The patients also judged the severity of their eczema daily on a visual analogue scale. Both groups improved in terms of eczema and DLQI. However, the clinical scoring demonstrated that once daily application of corticosteroid was superior to twice daily application in diminishing eczema, especially in the group of patients with lower eczema scores at inclusion. Twice daily use of corticosteroids was not superior to once daily use in treating eczema. On the contrary, the clinical assessment showed a larger benefit from once daily treatment compared with twice daily, especially in the group of patients with a moderate eczema at inclusion. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

  13. Lung Deflation and Cardiovascular Structure and Function in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial.

    Stone, Ian S; Barnes, Neil C; James, Wai-Yee; Midwinter, Dawn; Boubertakh, Redha; Follows, Richard; John, Leonette; Petersen, Steffen E

    2016-04-01

    Patients with chronic obstructive pulmonary disease develop increased cardiovascular morbidity with structural alterations. To investigate through a double-blind, placebo-controlled, crossover study the effect of lung deflation on cardiovascular structure and function using cardiac magnetic resonance. Forty-five hyperinflated patients with chronic obstructive pulmonary disease were randomized (1:1) to 7 (maximum 14) days inhaled corticosteroid/long-acting β2-agonist fluticasone furoate/vilanterol 100/25 μg or placebo (7-day minimum washout). Primary outcome was change from baseline in right ventricular end-diastolic volume index versus placebo. There was a 5.8 ml/m(2) (95% confidence interval, 2.74-8.91; P volume index and a 429 ml (P volume with fluticasone furoate/vilanterol versus placebo. Left ventricular end-diastolic and left atrial end-systolic volumes increased by 3.63 ml/m(2) (P = 0.002) and 2.33 ml/m(2) (P = 0.002). In post hoc analysis, right ventricular stroke volume increased by 4.87 ml/m(2) (P = 0.003); right ventricular ejection fraction was unchanged. Left ventricular adaptation was similar; left atrial ejection fraction improved by +3.17% (P Pulmonary artery pulsatility increased in two of three locations (main +2.9%, P = 0.001; left +2.67%, P = 0.030). Fluticasone furoate/vilanterol safety profile was similar to placebo. Pharmacologic treatment of chronic obstructive pulmonary disease has consistent beneficial and plausible effects on cardiac function and pulmonary vasculature that may contribute to favorable effects of inhaled therapies. Future studies should investigate the effect of prolonged lung deflation on intrinsic myocardial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01691885).

  14. Miliarial type pseudolymphoma mimicking as granulomatous rosacea

    Gharaei Nejad Kaveh

    2017-07-01

    Full Text Available Miliarial type lymphocytoma cutis is a rare type of psuedolymphoma which is described by numerous semi-translucent papules on the sun exposed regions. Herein, we present a 25-year-old woman with numerous permanent translucent tiny papules on the face. Microscopic examination revealed dense infiltration of lymphocytes in the reticular dermis with lymphoid follicle formation and significant B-cell lymphocytes in immunohistochemistry study. She was diagnosed as miliarial type pseudolymphoma and treated with topical momethasone furoate ointment and oral hydroxychloroquine with a good response.

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

    Fabbri Leonardo M

    2010-10-01

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

  16. Differences between nisoldipine and lisinopril on glomerular filtration rates and albuminuria in hypertensive IDDM patients with diabetic nephropathy during the first year of treatment

    Rossing, P; Tarnow, L; Boelskifte, S

    1997-01-01

    were required in 10 nisoldipine- and 8 lisinopril-treated patients. Every 3 months, 24-h ambulatory blood pressure (TM2420, A&D, Tokyo, Japan) and albuminuria in three 24-h samples (enzyme immunoassay) were measured; GFR (51Cr-EDTA plasma clearance) was recorded every 6 months. Mean arterial blood......-blind, double-dummy, randomized, controlled study comparing nisoldipine (20-40 mg once daily) with lisinopril (10-20 mg once daily) in 52 hypertensive IDDM subjects with diabetic nephropathy. Three patients dropped out, and results for the remaining 49 (25 nisoldipine, 24 lisinopril) are presented. Diuretics...... pressure (24 h) was reduced from (mean +/- SE) 108 +/- 3 mmHg at baseline to 101 +/- 2 in average during treatment in the lisinopril group and from 105 +/- 2 to 103 +/- 2 in the nisoldipine group (P = 0.06 comparing changes in the two groups). Albuminuria was reduced 47% (95% CI 21-65) in the lisinopril...

  17. Feeding motivation and plasma metabolites in pregnant sows fed diets rich in dietary fiber either once or twice daily

    Jensen, Margit Bak; Pedersen, Lene Juul; Theil, Peter Kappel

    2012-01-01

    in an operant conditioning test, and samples of peripheral blood were taken in a balanced design, at 0900, 1200, 1900, and 0700 h, corresponding to 1, 4, 11, and 23 h after feeding for restricted sows fed once daily. No differences in the feeding motivation were found between the 4 restricted diets at any......, indicating that feeding twice daily reduced feeding motivation during the night compared with feeding once daily. Among restricted-fed sows, plasma concentrations of short-chain fatty acids (SCFA) were greater in sows fed high-fiber diets compared with the control (P = 0.02). Nonesterified fatty acid...... level of fiber in the diet of restrictedly fed sows did not reduce their feeding motivation irrespective of fiber source....

  18. The role of rasagiline in the treatment of Parkinson's disease.

    Leegwater-Kim, Julie; Bortan, Elena

    2010-05-25

    Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting 1% to 2% of people older than 60 years. Treatment of PD consists of symptomatic therapies while neuroprotective strategies have remained elusive. Rasagiline is a novel, potent, and irreversible monoamine oxidase type B (MAO-B) inhibitor which has been approved for treatment of PD. Rasagiline inhibits MAO-B more potently than selegiline and has the advantage of once-daily dosing. In several large, randomized, placebo-controlled trials, rasagiline has demonstrated efficacy as monotherapy in early PD and as adjunctive therapy in advanced PD. In addition, rasagiline has been shown to have neuroprotective effects in in vitro and in vivo studies. The recently completed delayed-start ADAGIO (Attenuation of Disease Progression with Azilect Given Once-daily) trial suggests a potential disease-modifying effect for rasagiline 1 mg/day, though the clinical import of this finding has yet to be established.

  19. The role of rasagiline in the treatment of Parkinson’s disease

    Leegwater-Kim, Julie; Bortan, Elena

    2010-01-01

    Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting 1% to 2% of people older than 60 years. Treatment of PD consists of symptomatic therapies while neuroprotective strategies have remained elusive. Rasagiline is a novel, potent, and irreversible monoamine oxidase type B (MAO-B) inhibitor which has been approved for treatment of PD. Rasagiline inhibits MAO-B more potently than selegiline and has the advantage of once-daily dosing. In several large, randomized, placebo-controlled trials, rasagiline has demonstrated efficacy as monotherapy in early PD and as adjunctive therapy in advanced PD. In addition, rasagiline has been shown to have neuroprotective effects in in vitro and in vivo studies. The recently completed delayed-start ADAGIO (Attenuation of Disease Progression with Azilect Given Once-daily) trial suggests a potential disease-modifying effect for rasagiline 1 mg/day, though the clinical import of this finding has yet to be established. PMID:20517484

  20. Rationale and design of MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF)

    Pitt, Bertram; Anker, Stefan D; Böhm, Michael

    2015-01-01

    dysfunction. METHODS AND RESULTS: The MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF; NCT01807221) is a multicentre, randomized, double-blind, active-comparator-controlled, six-parallel-group, phase 2b dose-finding study. In total, 1060 patients with HFrEF and concomitant type...... 2 diabetes mellitus and/or chronic kidney disease (CKD) will be randomized within 7 days of emergency presentation to hospital for worsening chronic HF to receive finerenone (one of five doses in the range 2.5-20.0 mg once daily) or eplerenone (25 mg every second day to 50 mg once daily for 90 days...

  1. Renal effects of aliskiren compared with and in combination with irbesartan in patients with type 2 diabetes, hypertension, and albuminuria

    Persson, Frederik; Rossing, Peter; Reinhard, Henrik

    2009-01-01

    throughout the study. The primary end point was a change in albuminuria. Secondary measures included change in 24-h blood pressure and glomerular filtration rate (GFR). RESULTS: Placebo geometric mean albuminuria was 258 mg/day (range 84-2,361), mean +/- SD 24-h blood pressure was 140/73 +/- 15/8 mm...... with type 2 diabetes, hypertension, and albuminuria (>100 mg/day) were randomly assigned to four 2-month treatment periods in random order with placebo, 300 mg aliskiren once daily, 300 mg irbesartan once daily, or the combination using identical doses. Patients received furosemide in a stable dose......-79), more than either monotherapy (P blood pressure was reduced 3/4 mmHg by aliskiren (NS/P = 0.009), 12/5 mmHg by irbesartan (P

  2. Rivaroxaban with or without aspirin in stable cardiovascular disease

    Eikelboom, John W; Connolly, Stuart J; Bosch, Jackie

    2017-01-01

    BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive...... rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after...... a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P

  3. Antianginal efficacy of the combination of felodipine-metoprolol 10/100 mg compared with each drug alone in patients with stable effort-induced angina pectoris

    Emanuelsson, H; Egstrup, K; Nikus, K

    1999-01-01

    OBJECTIVE: The primary objective of this randomized, double-blind, parallel group trial was to compare the antianginal and antiischemic efficacy of a combination tablet of felodipine-metoprolol 10/100 mg once daily with both drugs given separately once daily in patients with stable effort......-daily treatment with either felodipine-metoprolol 10/100 mg, felodipine 10 mg, or metoprolol 100 mg. The duration of active double-blind treatment was 4 weeks. There were 3 primary efficacy variables in the study; time until end of exercise, time until onset of chest discomfort, and time until 1-mm ST depression...... during a standardized exercise test. RESULTS: The number of patients randomized was 397. There was a statistically significant improvement in time until end of exercise with felodipine-metoprolol 10/100 mg compared with metoprolol 100 mg (P =.04) and felodipine 10 mg compared with metoprolol 100 mg ( P...

  4. Circulating ghrelin concentrations fluctuate relative to nutritional status and influence feeding behavior in cattle.

    Wertz-Lutz, A E; Knight, T J; Pritchard, R H; Daniel, J A; Clapper, J A; Smart, A J; Trenkle, A; Beitz, D C

    2006-12-01

    The objective of these experiments was to establish the relationship of plasma ghrelin concentrations with feed intake and hormones indicative of nutritional state of cattle. In Exp.1, 4 steers (BW 450 +/- 14.3 kg) were used in a crossover design to compare plasma ghrelin concentrations of feed-deprived steers with those of steers allowed to consume feed and to establish the relationship of plasma ghrelin concentrations with those of GH, insulin (INS), glucose (GLU), and NEFA. After adaptation to a once-daily feed offering (0800), 2 steers continued the once-daily feeding schedule (FED), whereas feed was withheld from the other 2 steers (FAST). Serial blood samples were collected via indwelling jugular catheter from times equivalent to 22 h through 48 h of feed deprivation. Average plasma ghrelin concentrations were greater (P ruminants.

  5. Atorvastatin induced thrombocytopenia: A case report and review of literature

    Saibal Moitra

    2016-01-01

    Full Text Available A 65-year-old hypertensive male, with co-existing benign prostatic hyperplasia for last 5 years was on tab telmisartan 40 mg and tab tamsulosin 0.4 mg, both once daily. He was found dyslipidemic on a routine investigation and was put on tab atorvastatin 10 mg once daily. The patient developed a petechial rash and bleeding from gums within a week of starting atorvastatin, and his platelet count dropped to 15,000/cmm. Atorvastatin was suspected to be the offender as no other causes of thrombocytopenia could be implicated. Atorvastatin was discontinued and intravenous steroid and platelet transfusion given. Platelet count improved gradually and became normal after 10 days. Causality assessment as per the Naranjo algorithm revealed a "probable association" with atorvastatin therapy.

  6. The design and discovery of lixisenatide for the treatment of type 2 diabetes mellitus

    Christensen, Mikkel; Miossec, Patrick; Larsen, Bjarne Due

    2014-01-01

    INTRODUCTION: Lixisenatide is a once-daily short-acting glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) used in the treatment of type 2 diabetes mellitus (T2DM). It is used in combination with oral antidiabetics and/or basal insulin in patients inadequately controlled on these medicati......INTRODUCTION: Lixisenatide is a once-daily short-acting glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) used in the treatment of type 2 diabetes mellitus (T2DM). It is used in combination with oral antidiabetics and/or basal insulin in patients inadequately controlled...... with the other GLP-1RAs. The combination of two injectables, such as basal insulin to lower fasting plasma glucose and a GLP-1RA that curtails PPG excursions, is clinically valuable and could differentiate lixisenatide from other GLP-1RAs, especially from those continuously acting GLP-1RAs with little effect...

  7. Local control and functional results after twice-daily radiotherapy for Ewing's sarcoma of the extremities

    Bolek, Timothy W.; Marcus, Robert B.; Mendenhall, Nancy Price; Scarborough, Mark T.; Graham-Pole, John

    1996-01-01

    Purpose: Radiotherapy (RT) has been the predominant local treatment for Ewing's sarcoma of bone at the University of Florida. Twice-daily hyperfractionated RT was initiated in 1982 to improve local control and functional outcome. This retrospective review compares the results of once-daily vs. twice-daily RT in patients with primary Ewing's sarcoma of an extremity, with emphasis on functional outcome. Methods and Materials: Between June 1971 and January 1990, 37 patients were treated at the University of Florida for nonmetastatic Ewing's sarcoma of bone with a primary lesion in an extremity. Three patients underwent amputation. Of 34 patients treated with RT, 31 had RT alone and 3 had a combination of RT and local excision. Before 1982, 14 patients received once-daily RT; since 1982, 17 patients have received twice-daily RT. Doses of once-daily RT varied from 47 to 61 Gy at 1.8-2 Gy per fraction. Doses of twice-daily RT varied, depending on the response of the soft-tissue component of the tumor to chemotherapy, and ranged from 50.4 to 60 Gy at 1.2 Gy per fraction. Some patients in the twice-daily RT group also received total body irradiation 1-3 months after local RT as part of a conditioning regimen before marrow-ablative therapy with stem cell rescue. They received either 8 Gy in two once-daily fractions or 12 Gy in six twice-daily fractions. The six patients who received surgery were excluded from local control analysis. Local control rates were calculated using the Kaplan-Meier (actuarial) method. Fifteen patients had a formal functional evaluation. Results: In the 31 patients treated with RT alone, the actuarial local control rate at 5 years was 81% for patients treated twice daily and 77% for those treated once daily (p = NS). No posttreatment pathologic fractures occurred in patients treated twice daily, whereas five fractures occurred in those treated once daily (p = 0.01). On functional evaluation, less loss in range of motion (15 deg. vs. 28 deg. of loss

  8. Control of hypertension with single daily doses of sotalol hydrochloride.

    Gabriel, R

    A study was carried out in 12 previously untreated hypertensive patients to assess the efficacy of sotalol given in a once-daily dosage regimen. After an initial dosage titration period (mean 3 weeks) during which diastolic pressure was stabilized at less than 100 mmHg, all patients were satisfactorily maintained on a constant once-daily dose of sotalol for 3 months. Eight of the 12 patients required 320 mg or less daily (mean dose 190 mg). Whilst blood pressure remained controlled for at least 26 hours after daily doses the pulse rate, counted at the same time, showed escape from beta-blockade. Side-effects (vivid dreams) were reported in only 1 patient.

  9. [Efficacy of low-dose tadalafil on ED assessed by Self-Esteem and Relationship Questionnaire].

    Li, Jing-Ping; Li, Fei; Guo, Wen-Bin; Zhou, Qi-Zhao; Liu, Cun-Dong; Mao, Xiang-Ming; Tan, Wan-Long; Zheng, Shao-Bin

    2010-12-01

    To explore the effects of low-dose oral tadalafil on self-esteem, confidence and sexual relationship in ED patients. We treated 17 ED patients with oral tadalafil at the low dose of 5 mg once daily for 12 weeks, and used the paired t test to compare their scores on The Self-Esteem and Relationship Questionnaire (SEAR) and IIEF-5 and the results of nocturnal penile tumescence (NPT) obtained by nocturnal electrobioimpedance volumetric assessment (NEVA) before and after the medication. The scores on SEAR and IIEF-5 were significantly increased (P P Low-dose oral tadalafil once daily can significantly improve the self-esteem, confidence, sexual relationship satisfaction and NPT of ED patients.

  10. Promotion of myelopoiesis in myelosuppressed mice by Ganoderma lucidum polysaccharides

    Xiao Ling Zhu

    2012-02-01

    Full Text Available Ganoderma lucidum polysaccharides (Gl-PS exhibit potent immunomodulating effects. Immunomodulation plays an important role in hematopoiesis. To investigate the mechanism by which Gl-PS promote myelopoiesis during myelosuppression induced by cyclophosphamide, mice were injected intraperitoneally (i.p. once daily with 2.5 mg/kg of Gl-PS or with vehicle (i.e. sterile physiological saline as negative controls for 10 days and were treated i.p. once daily with cyclophosphamide (100 mg/kg on days 2 through 4. In the present study, we demonstrated that Gl-PS selectively bind to bone marrow stromal cells, stimulate the secretion of hematopoietic growth factors and enhance the clonogenic activities of hematopoietic and stromal cells to promote hematopoiesis.

  11. The efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep vein thrombosis in elective cancer surgery. A double blind randomized multicentre trail with venographic assesment

    Bergkvist, A; Eldor, A; Thorlacius-Ussing, O.

    1997-01-01

    BACKGROUND: Surgery for malignant disease carries a high risk of deep vein thrombosis. The aim of this study was to evaluate the prophylactic effect of a low molecular weight heparin, enoxaparin, 40 mg once daily, beginning 2 h before surgery, compared with that of unfractionated low-dose heparin...... three times daily. METHODS: Patients included were over 40 years of age and undergoing planned elective curative abdominal or pelvic surgery for cancer. The study was designed as a prospective double-blind randomized multicentre trial with participating departments from ten countries. Primary outcome...... severe thrombocytopenia. There were no differences in mortality at either 30 days or 3 months. CONCLUSION: Enoxaparin, 40 mg once daily, is as safe and effective as unfractionated heparin three times daily in preventing venous thromboembolism in patients undergoing major elective surgery for abdominal...

  12. A randomized, controlled trial of 3.0 mg of Liraglutide in weight management

    Pi-Sunyer, Xavier; Astrup, Arne; Fujioka, Ken

    2015-01-01

    Background Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagon-like peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg...... or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were...... with liraglutide were mild or moderate nausea and diarrhea. Serious events occurred in 6.2% of the patients in the liraglutide group and in 5.0% of the patients in the placebo group. Conclusions In this study, 3.0 mg of liraglutide, as an adjunct to diet and exercise, was associated with reduced body weight...

  13. [LIRAGUTIDE AT A DOSE OF 3.0 MG (SAXENDA): NEW INDICATION FOR THE TREATMENT OF OBESITY].

    Scheen, A J

    2016-05-01

    Liraglutide is an analogue of Glucagon-Like Peptide-1 (GLP-1) already indicated under the trade name of Victoza for the treatment of type 2 diabetes, at usual doses of 1.2 or 1.8 mg as once daily subcutaneous injection. It is henceforth indicated at a dose of 3.0 mg, also as once daily subcutaneous injection, for the treatment of obesity or overweight with comorbidities under the trade name of Saxenda, in combination with diet and exercise. Besides a specific action on the endocrine pancreas, mainly responsible for the antihyperglycaemic effect, liraglutide helps controlling appetite at the hypothamalic level. A specific programme of controlled trials (especially SCALE studies) demonstrated both efficacy and safety of the 3.0 mg dose of liraglutide in obese or overweight patients with various comorbidities.

  14. Lixisenatide for type 2 diabetes mellitus

    Christensen, Mikkel; Knop, Filip K; Vilsbøll, Tina

    2011-01-01

    Introduction: Type 2 diabetes mellitus (T2DM) is an increasing health problem worldwide. Glucagon-like peptide-1 (GLP-1) receptor agonists are an expanding drug class that target several of the pathophysiological traits of T2DM. Lixisenatide is a GLP-1 receptor agonist in development for once......-daily treatment of T2DM. Areas covered: Pharmacological, preclinical and clinical evidence demonstrating the applicability of lixisenatide for the treatment of T2DM are reviewed. Available data and pending clinical development are summarized, critically appraised and compared to competitor drugs. The most...... relevant papers and meeting abstracts published up to November 2010 are used as sources for this review. Expert opinion: Efficacy and safety in T2DM are demonstrated with lixisenatide in monotherapy and in combination with metformin. However, limited data with the intended once-daily 20 µg subcutaneous...

  15. Tiotropium HandiHaler(®) and Respimat(®) in COPD

    Halpin, David Mg; Dahl, Ronald; Hallmann, Christoph

    2015-01-01

    INTRODUCTION: Tiotropium is prescribed for the treatment of chronic obstructive pulmonary disease (COPD) and delivered via HandiHaler(®) (18 μg once daily) or Respimat(®) Soft Mist™ inhaler (5 μg once daily). The recent TIOtropium Safety and Performance In Respimat(®) (TIOSPIR™) study demonstrated...... randomized, double-blind, parallel-group, placebo-controlled, clinical trials in patients with COPD (treatment duration ≥4 weeks). Incidence rates, rate ratios (RRs), and 95% confidence intervals (CIs) were determined for HandiHaler(®) and Respimat(®) trials, both together and separately. RESULTS: In the 28...... groups remained lower than in placebo and similarly for FAEs. CONCLUSION: This analysis indicates that tiotropium is associated with lower rates of AEs, SAEs, and similar rates of FAEs than placebo when delivered via HandiHaler(®) or Respimat(®) (overall and separately) in patients with COPD....

  16. Differential effects of acute and repeated electrically and chemically induced seizures on ( sup 3 H)Nimodipine and ( sup 125 I)omega-conotoxin GVIA binding in rat brain

    Gleiter, C.H.; Cain, C.J.; Weiss, S.R.; Post, R.M.; Marangos, P.J. (National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (USA))

    1989-07-01

    ({sup 3}H)Nimodipine and high-affinity ({sup 125}I)omega-conotoxin GVIA (CgTX) binding were investigated in membranes from rat cerebral cortex, cerebellum, and hippocampus after electrically and chemically induced seizures. Animals were decapitated 30 min after a single electroconvulsive shock (ECS) or lidocaine-induced seizure and 24 h after the last of 10 once-daily ECS or six once-daily lidocaine-induced seizures. After a single ECS, ({sup 3}H)nimodipine and ({sup 125}I)CgTX binding sites decreased in cerebral cortex (by 10% and 17%, respectively). A downregulation of ({sup 3}H)nimodipine binding sites in hippocampus occurred after single and repeated lidocaine-induced seizures (by 24% and 11%, respectively), whereas ({sup 125}I)CgTX binding remained unaltered. An earlier report on changes in ({sup 3}H)nitrendipine binding after chronic ECS in cortex and hippocampus was not confirmed.

  17. Development of Modified-Release Tablets of Zolpidem Tartrate by Biphasic Quick/Slow Delivery System

    Mahapatra, Anjan Kumar; Sameeraja, N. H.; Murthy, P. N.

    2014-01-01

    Zolpidem tartrate is a non-benzodiazepine analogue of imidazopyridine of sedative and hypnotic category. It has a short half-life with usual dosage regimen being 5 mg, two times a day, or 10 mg, once daily. The duration of action is considered too short in certain circumstances. Thus, it is desirable to lengthen the duration of action. The formulation design was implemented by preparing extended-release tablets of zolpidem tartrate using the biphasic delivery system technology, where sodium s...

  18. Toxicokinetiek van benzo(a)pyreen bij de Riv:TOX rat na herhaalde orale toediening

    Olling M; Lusthof KJ; Kroese ED; Beenen J; Klaassen R; BFT

    1995-01-01

    Benzo(a)pyrene was administered once daily (30 mg/kg) by gavage to 12 male and 12 female Riv:TOX rats, for 15 days on five successive days per week, in the form of a solution in soy oil. Blood samples were taken over a period of 12 hours on the first day of administration (day 1) and on day 12 from

  19. Safety of polyethylene glycol 3350 solution in chronic constipation: randomized, placebo-controlled trial

    McGraw, Thomas

    2016-01-01

    Thomas McGraw Global Medical Affairs, Merck & Co., Inc., Kenilworth, NJ, USA Purpose: To evaluate the safety and tolerability of aqueous solution concentrate (ASC) of polyethylene glycol (PEG) 3350 in patients with functional constipation.Patients and methods: The patients who met Rome III diagnostic criteria for functional constipation were randomized in this multicenter, randomized, placebo-controlled, single-blind study to receive once daily dose of PEG 3350 (17 g) ASC or ...

  20. Development of Carcinogenesis Bioassay Models: Response of Small Fish Species to Various Classes of Carcinogens

    1991-12-20

    series by precision liquid dispensing syringe pumps (PLD-II, Hamilton Company, Reno, NV) and delivered through microbore tubing to a maximum of six...In a parallel study, inIwhich acrylonitrile was administered by stomach tube (olive oil carrier, 5 mg/kg, once daily, 3 times weekly, 52 weeks) no...actually are combinations of solute and microfine particulate test compound. These particulates can vary in both size distribution and quantity so

  1. Safety and convenience of once-weekly somapacitan in adult GH deficiency: a 26-week randomized, controlled trial.

    Johannsson, Gudmundur; Feldt-Rasmussen, Ulla; Håkonsson, Ida Holme; Biering, Henrik; Rodien, Patrice; Tahara, Shigeyuki; Toogood, Andrew; Rasmussen, Michael Højby

    2018-05-01

    Somapacitan is a reversible albumin-binding growth hormone (GH) derivative, developed for once-weekly administration. This study aimed to evaluate the safety of once-weekly somapacitan vs once-daily Norditropin ® . Local tolerability and treatment satisfaction were also assessed. 26-week randomized, controlled phase 3 safety and tolerability trial in six countries (Nbib2382939). Male or female patients aged 18-79 years with adult GH deficiency (AGHD), treated with once-daily GH for ≥6 months, were randomized to once-weekly somapacitan ( n  = 61) or once-daily Norditropin ( n  = 31) administered subcutaneously by pen. Both treatments were dose titrated for 8 weeks to achieve insulin-like growth factor I (IGF-I) standard deviation score (SDS) levels within the normal range, and then administered at a fixed dose. Outcome measures were adverse events (AEs), including injection site reactions; occurrence of anti-somapacitan/anti-GH antibodies and change in treatment satisfaction, assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). Mean IGF-I SDS remained between 0 and 2 SDS throughout the trial in both groups. AEs were mostly mild or moderate and transient in nature. The most common AEs were nasopharyngitis, headache and fatigue in both groups. More than 1500 somapacitan injections were administered and no clinically significant injection site reactions were reported. No anti-somapacitan or anti-GH antibodies were detected. The TSQM-9 score for convenience increased significantly more with somapacitan vs Norditropin ( P  = 0.0171). In this 26-week trial in patients with AGHD, somapacitan was well tolerated and no safety issues were identified. Once-weekly somapacitan was reported to be more convenient than once-daily Norditropin. © 2018 The authors.

  2. The role of rasagiline in the treatment of Parkinson?s disease

    Leegwater-Kim, Julie; Bortan, Elena

    2010-01-01

    Parkinson?s disease (PD) is the second most common neurodegenerative disorder, affecting 1% to 2% of people older than 60 years. Treatment of PD consists of symptomatic therapies while neuroprotective strategies have remained elusive. Rasagiline is a novel, potent, and irreversible monoamine oxidase type B (MAO-B) inhibitor which has been approved for treatment of PD. Rasagiline inhibits MAO-B more potently than selegiline and has the advantage of once-daily dosing. In several large, randomiz...

  3. Saxagliptin for type 2 diabetes

    Chacra,

    2010-01-01

    Antonio R Chacra, MDDiabetes Center, Federal University of São Paulo, BrazilAbstract: Saxagliptin (Onglyza™) is a potent, selective, once-daily dipeptidyl peptidase-4 (DPP-4) inhibitor indicated for improving glycemic control in patients with type 2 diabetes (T2D). By blocking DPP-4, saxagliptin increases and prolongs the effects of incretins, a group of peptide hormones released by intestinal cells after meals, which stimulate glucose-dependent insulin secretion to lower...

  4. Efficacy of Cefquinome against Escherichia coli Environmental Mastitis Assessed by Pharmacokinetic and Pharmacodynamic Integration in Lactating Mouse Model

    Yang Yu

    2017-08-01

    Full Text Available This work investigates the pharmacodynamic effectiveness of cefquinome against environmental Escherichia coli mastitis infection, following an intramammary administration. We established the pharmacokinetic and pharmacodynamic (PK/PD model in lactating mice. The PK/PD parameters were identified to achieve an antibacterial efficacy as indicated by PD activity, cytokine expression and PK/PD simulation. From our findings, given an 200 μg/gland dose once daily can achieve a considerable therapeutic effectiveness in experimental circumstance.

  5. Oxcarbazepine Induced Maculopapular Rash - A Case Report

    Biswas, Arunava; Mitra, Ritabrata; Sen, Sukanta; Pal, Agnik; Tripathi, Santanu Kumar

    2015-01-01

    Unlike carbamazepine, newer anti epileptic drug like oxcarbazepine, reports fewer side effects. In this report we describe a case of oxcarbazepine induced maculopapular rash probably happened because of a drug interaction with isoniazid, and a brief review of the existing literature is presented herewith. A 40-year-old male patient received oxcarbazepine 300mg twice daily along with other anti-tubercular drugs including isoniazid (300mg) once daily since two days. Extensive cutaneous rash wit...

  6. Characteristics of refractory gastroesophageal reflux disease (GERD) symptoms -is switching proton pump inhibitors based on the patient's CYP2C19 genotype an effective management strategy?

    Takeuchi, Toshihisa; Oota, Kazuhiro; Harada, Satoshi; Edogawa, Shoko; Kojima, Yuichi; Sanomura, Makoto; Sakaguchi, Masahiro; Hayashi, Katsuyoshi; Hongoh, Yasushi; Itabashi, Tsukasa; Kitae, Hidehiro; Hoshimoto, Masahiro; Takeuchi, Nozomi; Higuchi, Kazuhide

    2015-01-01

    We investigated factors related to proton pump inhibitor (PPI) -refractory gastroesophageal reflux disease (GERD) symptoms, particularly with respect to acid, the CYP2C19 genotype and psychological aspects. Patients with an Frequency Scale for the Symptoms of GERD (FSSG) score of ≥8 after the initial treatment were switched to therapy with rabeprazole at a dose of 20 mg once daily for eight weeks. We investigated the rate of improvement in PPI-refractory GERD symptoms, background factors, the Hospital Anxiety and Depression Scale (HADS) score and the CYP2C19 genotype. Patients Sixty patients endoscopically diagnosed with reflux esophagitis within the past six months who had received omeprazole at a dose of 20 mg once daily for eight weeks or longer were enrolled. In 71.6% of the patients, the FSSG score decreased to GERD symptoms. Significant factors related to omeprazole-refractory GERD symptoms included a longer disease duration (p=0.0004) and higher HADS score (p=0.01). Among the omeprazole-refractory cases, only 23.5% of the patients showed symptom improvement after switching to rabeprazole. There were no significant differences in the average scores for FSSG (p=0.089) or HADS (p=0.182), before or after the drug change. A total of 92% of the rabeprazole poor responders were homo/hetero extensive metabolizers for the CYP2C19 genotype. Our findings suggest that switching the PPI from omeprazole (20 mg once daily) to rabeprazole (20 mg once daily) is not a significant effective therapeutic strategy for improving PPI-refractory GERD symptoms, taking into consideration possible psychometric factors and patients who require stronger acid suppression than that achieved with a double dose of PPIs for PPI-refractory GERD symptoms.

  7. Antitumor effects of regorafenib and sorafenib in preclinical models of hepatocellular carcinoma

    Kissel, Maria; Berndt, Sandra; Fiebig, Lukas; Kling, Simon; Ji, Qunsheng; Gu, Qingyang; Lang, Tina; Hafner, Frank-Thorsten; Teufel, Michael; Zopf, Dieter

    2017-01-01

    The purpose of this study was to investigate the antitumor activity of regorafenib and sorafenib in preclinical models of HCC and to assess their mechanism of action by associated changes in protein expression in a HCC-PDX mouse model. Both drugs were administered orally once daily at 10 mg/kg (regorafenib) or 30 mg/kg (sorafenib), which recapitulate the human exposure at the maximally tolerated dose in mice. In a H129 hepatoma model, survival times differed significantly between regorafenib ...

  8. STRike - characteristics of HIV-1-infected patients treated with a single-tablet regimen in daily clinical practice

    S Esser; H Heiken; L Gallo; S Schellberg; M Schlag; A Moll; R Pauli; A Stoehr; O Degen; H Jaeger; C Stephan; G Fätkenheuer

    2012-01-01

    The life-long antiretroviral treatment of HIV-1 infection requires effective and well tolerated medications complemented by high rates of adherence in order to achieve viral suppression, immunologic reconstitution and to prevent the development of resistance. Single-tablet regimens (STRs), combining a full antiretroviral regimen in one tablet taken once daily, have been designed to achieve high adherence and better long-term outcomes. “STRike” is the first cohort study, describi...

  9. One and three doses of propranolol a day in hypertension.

    van den Brink, G; Boer, P; van Asten, P; Dorhout Mees, E J; Geyskes, G G

    1980-01-01

    In 26 patients with essential hypertension who were on continuous chlorthalidone therapy, 1 and 3 daily doses of propranolol were compared in a crossover study. Plasma propranolol levels and heart rates had larger daily fluctuations on single-dose therapy than on 3 times daily; plasma renin activity was more constant. There was no significant difference in blood pressures. Once-daily propranolol dosage was well tolerated and possibly gave less rise to the troublesome side effect of vivid dreaming.

  10. The effect of N-2-cyano-ethylamphetamine. HCl on total lipid contents of placenta and some material and fetal tissues of the rat.

    Kulay, L; Oliveira-Filho, R M; Siciliano, S F; Kulay, M N

    1978-12-01

    Female rats received 1.25 mg/kg body weight of N-2-cyano-ethylamphetamine. HCl (Fenproporex chlorhydrate) by oral route, once daily from the 5th to the 21st day of pregnancy, and compared to untreated pregnant rats, showed an increased total lipid content in maternal blood and fetal hearts; liver and heart have had total lipids decrease, while in placenta and fetal livers they were not observed significant differences.

  11. A Randomized Male Tolerance Study of Dapivirine Gel Following Multiple Topical Penile Exposures (MTN 012/IPM 010)

    Cranston, Ross D.; Hoesley, Craig; Carballo-Diéguez, Alex; Hendrix, Craig W.; Husnik, Marla; Levy, Lisa; Hall, Wayne; Soto-Torres, Lydia; Nel, Annalene M.

    2014-01-01

    Dapivirine (DPV) is a nonnucleoside reverse transcriptase inhibitor with a favorable safety profile following vaginal application. A penile tolerance study was conducted prior to further development of DPV as a candidate vaginal microbicide. Twenty-four circumcised and 24 uncircumcised (N=48) healthy HIV-negative male participants aged 18 years or older were randomized 2:1:1 to apply DPV 0.05% gel, matched placebo gel, or universal placebo gel, respectively, to their penis once daily for 7 se...

  12. The impact of treatment with indacaterol in patients with COPD

    Kerstjens, Huib A M; Deslée, Gaëtan; Dahl, Ronald

    2015-01-01

    BACKGROUND: Indacaterol is an inhaled, once-daily, ultra-long-acting β2-agonist for the treatment of chronic obstructive pulmonary disease (COPD). We report on the effectiveness of indacaterol and other bronchodilators compared with placebo in patients across the Global Initiative for Chronic...... treatment of COPD. Indacaterol 150 and 300 μg effectively improved lung function and symptoms in patients across all GOLD 2011 categories....

  13. USE OF EXTENDED-RELEASE PRAMIPEXOLE IN EARLY-STAGE PARKINSON’S DISEASE: DESCRIPTION OF A CLINICAL CASE

    N. V. Fedorova

    2014-11-01

    Full Text Available The paper considers a clinical case of early-stage mixed Parkinson’s disease (PD with significant affective disorders and restless legs syndrome. Once-daily extended-release pramipexole 3 mg significantly improved a patient’s status and led to regression of movement and affective disorders. The paper gives data on the efficacy of dopamine receptor agonists in treating PD and the benefits of their extended-release formulations.

  14. Efficacy and safety of tofacitinib in patients with active rheumatoid arthritis: review of key Phase 2 studies

    Fleischmann, Roy; Kremer, Joel; Tanaka, Yoshiya; Gruben, David; Kanik, Keith; Koncz, Tamas; Krishnaswami, Sriram; Wallenstein, Gene; Wilkinson, Bethanie; Zwillich, Samuel H.; Keystone, Edward

    2016-01-01

    Abstract Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here, the safety and efficacy data from five Phase 2 studies of tofacitinib in patients with RA are summarized. Tofacitinib 1?30 mg twice daily was investigated, as monotherapy and in combination with methotrexate, in patients with RA. Tofacitinib 20 mg once daily was investigated in one study. Tofacitinib 5 and 10 mg twice daily were selected for investigation in Phase 3 studies; therefore,...

  15. Angiotensin AT2-receptor stimulation improves survival and neurological outcome after experimental stroke in mice

    Schwengel, Katja; Namsolleck, Pawel; Lucht, Kristin

    2016-01-01

    /BL6J or AT2R-knockout mice (AT2-KO) underwent MCAO for 30 min followed by reperfusion. Starting 45 min after MCAO, mice were treated once daily for 4 days with either vehicle or C21 (0.03 mg/kg ip). Neurological deficits were scored daily. Infarct volumes were measured 96 h post-stroke by MRI. C21...

  16. Phase I evaluation of the effects of ketoconazole and rifampicin on cediranib pharmacokinetics in patients with solid tumours

    Lassen, U; Miller, W H; Hotte, S

    2013-01-01

    PURPOSE: To investigate any effect of a CYP3A4 inhibitor (ketoconazole) or inducer (rifampicin) on cediranib steady-state pharmacokinetics in patients with advanced solid tumours. METHODS: In two Phase I, open-label trials, patients received once-daily oral doses of cediranib alone [20 mg...... (ketoconazole study); 45 mg (rifampicin study)] for 7 days followed by cediranib at the same dose with ketoconazole 400 mg/day for 3 days or once-daily rifampicin 600 mg/day for 7 days, respectively. Patients then continued to receive once-daily cediranib. RESULTS: In the ketoconazole study, 46 patients were...... dosed; 38 were evaluable for C (ss,max), 36 for AUC(ss). gMean AUC(ss) and C (ss,max) for cediranib 20 mg increased by 21 % (94 % CI 9-35 %) and 26 % (94 % CI 10-43 %), respectively, in the presence of ketoconazole. In the rifampicin study, 64 patients were dosed; 44 were evaluable for C (ss,max) and 41...

  17. Rasagiline.

    Siddiqui, M Asif A; Plosker, Greg L

    2005-01-01

    Rasagiline is a second-generation potent, irreversible and selective inhibitor of monoamine-oxidase type B (MAO-B), which has been evaluated for the treatment of Parkinson's disease. Rasagiline also possesses neuroprotective properties that are independent of its MAO inhibitory activity. Unlike selegiline, rasagiline has no amphetamine-like metabolites and its major metabolite, 1-(R)-aminoindan, has demonstrated favourable pharmacological activity in experimental studies. Rasagiline has shown significant beneficial effects as monotherapy in the treatment of early Parkinson's disease. Monotherapy with rasagiline 1 or 2 mg once daily significantly attenuated the worsening of symptoms, compared with placebo, in patients with early Parkinson's disease in a randomised, double-blind trial (n = 404). Furthermore, patients treated with rasagiline for 12 months had less functional decline than patients whose treatment was delayed for 6 months (n = 371). In patients with moderate-to-advanced disease receiving background therapy with levodopa and additional anti-parkinsonian medications (n = 1159), rasagiline 0.5 or 1 mg once daily reduced the daily 'off' time by 0.49-0.94 hours relative to that in placebo recipients in two randomised, double-blind trials. The efficacy of rasagiline 1 mg once daily was similar to entacapone 200 mg administered with each levodopa dose. Rasagiline was generally well tolerated in clinical trials as both monotherapy and when administered with other antiparkinsonian drugs. Adverse events with rasagiline were generally similar in frequency to those seen in placebo or entacapone recipients.

  18. Severe Hypernatremic Dehydration and Lower Limb Gangrene in an Infant Exposed to Lamotrigine, Aripiprazole, and Sertraline in Breast Milk.

    Morin, Caroline; Chevalier, Isabelle

    Hypernatremic dehydration is well described in exclusively breastfed neonates, although life-threatening complications are rarely reported. The present article describes a case of severe hypernatremic dehydration in a previously healthy term neonate. Other published cases of severe complications of hypernatremic dehydration are discussed. The exclusively breastfed neonate described had severe hypernatremic dehydration because of inadequate milk intake, with disseminated intravascular coagulation and right lower limb gangrene that required amputation of all five toes and surgical debridement of the metatarsals. The usual etiology of hypernatremic dehydration in this age group is insufficient breast milk intake. Here, the infant's mother was treated for bipolar disorder with lamotrigine 250 mg orally once daily, aripiprazole 15 mg orally once daily, and sertraline 100 mg orally once daily. Awareness of these complications should prompt close follow-up of the infant with poor weight gain. The role of maternal medication as a risk factor for hypernatremic dehydration among exclusively breastfed infants needs to be further explored.

  19. Does altered fractionation influence the risk of radiation-induced optic neuropathy?

    Bhandare, Niranjan; Monroe, Alan T.; Morris, Christopher G.; Bhatti, M. Tariq; Mendenhall, William M.

    2005-01-01

    Purpose: To analyze the parameters that influence the risk of radiation-induced optic neuropathy (RION) after radiotherapy for head-and-neck tumors. Methods and Materials: Between 1964 and 2000, 273 patients with tumors of the nasopharynx, paranasal sinuses, nasal cavity, and hard palate adenoid cystic carcinomas were treated with curative intent and had radiation fields that included the optic nerves and/or chiasm. Patients were followed for at least 1 year after radiotherapy. Results: Radiation-induced optic neuropathy developed in 32 eyes of 24 patients (9%). The 5-year rates of freedom from RION according to the total dose and once- vs. twice-daily fractionation were as follows: ≤63 Gy once daily, 95%; ≤63 Gy twice daily, 98%; >63 Gy once daily, 78%; and >63 Gy twice daily, 91%. Multivariate analysis revealed that the total dose affected the risk of RION (p = 0.0047), with patient age (p = 0.0909), once-daily vs. twice-daily fractionation (p = 0.0684), and overall treatment time (p = 0.0972) were marginally significant. The use of adjuvant chemotherapy did not significantly influence the likelihood of developing RION. Conclusion: The likelihood of developing RION is primarily influenced by the total dose. Hyperfractionation may reduce the risk of experiencing this complication

  20. The new trends in theophylline therapy

    Aida Mehmedagić

    2002-02-01

    Full Text Available Sustained-release theophylline pellets formulation for once-daily evening administration significantly improved patients compliance and adjusted serum levels profile of the drug. The patients conversion from i.v. to p.o. therapy is one of the most critical steps in the treatment of asthma according to its chronopathophysiological character. In our study we have examined safety and efficiency of this conversion in twelve hospitalised asthmatic patients who were given the new sustained-release theophylline pellets formulation for once-daily evening administration. The lung function parameters (FEV1, VC, RV, and Rt and serum theophylline concentrations were monitored. So, the values obtained for the last day of i.v. therapy and the fifth day of p.o. therapy were compared. We found that 75% of the patients had no change or improved lung function on the conversion. Our results indicate that this conversion from i.v. to p.o. theophylline therapy is safe and could be efficacious. Also, the maximum theophylline serum levels could safely be predicted by measuring only one serum concentration in p.o. therapy with sustained-release theophylline pellets formulation for once-daily evening administration.

  1. Pharmacokinetics of total and unbound darunavir in HIV-1-infected pregnant women.

    Colbers, Angela; Moltó, José; Ivanovic, Jelena; Kabeya, Kabamba; Hawkins, David; Gingelmaier, Andrea; Taylor, Graham; Weizsäcker, Katharina; Sadiq, S Tariq; Van der Ende, Marchina; Giaquinto, Carlo; Burger, David

    2015-02-01

    To describe the pharmacokinetics of darunavir in pregnant HIV-infected women in the third trimester and post-partum. This was a non-randomized, open-label, multicentre, Phase IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe. HIV-infected pregnant women treated with darunavir (800/100 mg once daily or 600/100 mg twice daily) as part of their combination ART were included. Pharmacokinetic curves were recorded in the third trimester and post-partum. A cord blood sample and maternal sample were collected. The study is registered at ClinicalTrials.gov under number NCT00825929. Twenty-four women were included in the analysis [darunavir/ritonavir: 600/100 mg twice daily (n=6); 800/100 mg once daily (n=17); and 600/100 mg once daily (n=1)]. Geometric mean ratios of third trimester versus post-partum (90% CI) were 0.78 (0.60-1.00) for total darunavir AUC0-tau after 600/100 mg twice-daily dosing and 0.67 (0.56-0.82) for total darunavir AUC0-tau after 800/100 mg once-daily dosing. The unbound fraction of darunavir was not different during pregnancy (12%) compared with post-partum (10%). The median (range) ratio of darunavir cord blood/maternal blood was 0.13 (0.08-0.35). Viral load close to delivery was HIV-negative and no congenital abnormalities were reported. Darunavir AUC and Cmax were substantially decreased in pregnancy for both darunavir/ritonavir regimens. This decrease in exposure did not result in mother-to-child transmission. For antiretroviral-naive patients, who are adherent, take darunavir with food and are not using concomitant medication reducing darunavir concentrations, 800/100 mg of darunavir/ritonavir once daily is adequate in pregnancy. For all other patients 600/100 mg of darunavir/ritonavir twice daily is recommended during pregnancy. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Coordination compounds of titanium, zirconium, tin, thorium and uranium

    Deshpande, S.G.; Jain, S.C.

    1990-01-01

    Reactions of isatin, furoic acid and picolinic acid have been carried out with titanium tetrachloride, tin tetrachloride, thorium tetrachloride, zirconyl chloride and uranyl nitrate. While 2:3(metal:ligand) type compounds of isatin have been obtained with Ti(IV) and Sn(IV), zirconium(IV), thorium(IV), and uranium(VI) do not react with the ligand under similar experimental conditions. Furoic acid (FAH) and picolinic acid(PicH) form various chloro furoates and picolinates when reacted with TiCl 4 , ZrOCl 2 and ThCl 4 , but do not react with SnCl 4 . The various compounds synthesised have been characterised on the basis of elemental analysis, infrared studies, conductivity and thermogravimetric measurements. (author). 1 tab., 10 refs

  3. From iron coordination compounds to metal oxide nanoparticles

    Mihail Iacob

    2016-12-01

    Full Text Available Various types, shapes and sizes of iron oxide nanoparticles were obtained depending on the nature of the precursor, preparation method and reaction conditions. The mixed valence trinuclear iron acetate, [Fe2IIIFeIIO(CH3COO6(H2O3]·2H2O (FeAc1, μ3-oxo trinuclear iron(III acetate, [Fe3O(CH3COO6(H2O3]NO3∙4H2O (FeAc2, iron furoate, [Fe3O(C4H3OCOO6(CH3OH3]NO3∙2CH3OH (FeF, iron chromium furoate, FeCr2O(C4H3OCOO6(CH3OH3]NO3∙2CH3OH (FeCrF, and an iron complex with an original macromolecular ligand (FePAZ were used as precursors for the corresponding oxide nanoparticles. Five series of nanoparticle samples were prepared employing either a classical thermal pathway (i.e., thermal decomposition in solution, solvothermal method, dry thermal decomposition/calcination or using a nonconventional energy source (i.e., microwave or ultrasonic treatment to convert precursors into iron oxides. The resulting materials were structurally characterized by wide-angle X-ray diffraction and Fourier transform infrared, Raman, energy-dispersive X-ray, and X-ray fluorescence spectroscopies, as well as thermogravimetric analysis. The morphology was characterized by transmission electron microscopy, atomic force microscopy and dynamic light scattering. The parameters were varied within each route to fine tune the size and shape of the formed nanoparticles.

  4. From iron coordination compounds to metal oxide nanoparticles.

    Iacob, Mihail; Racles, Carmen; Tugui, Codrin; Stiubianu, George; Bele, Adrian; Sacarescu, Liviu; Timpu, Daniel; Cazacu, Maria

    2016-01-01

    Various types, shapes and sizes of iron oxide nanoparticles were obtained depending on the nature of the precursor, preparation method and reaction conditions. The mixed valence trinuclear iron acetate, [Fe 2 III Fe II O(CH 3 COO) 6 (H 2 O) 3 ]·2H 2 O (FeAc1), μ 3 -oxo trinuclear iron(III) acetate, [Fe 3 O(CH 3 COO) 6 (H 2 O) 3 ]NO 3 ∙4H 2 O (FeAc2), iron furoate, [Fe 3 O(C 4 H 3 OCOO) 6 (CH 3 OH) 3 ]NO 3 ∙2CH 3 OH (FeF), iron chromium furoate, FeCr 2 O(C 4 H 3 OCOO) 6 (CH 3 OH) 3 ]NO 3 ∙2CH 3 OH (FeCrF), and an iron complex with an original macromolecular ligand (FePAZ) were used as precursors for the corresponding oxide nanoparticles. Five series of nanoparticle samples were prepared employing either a classical thermal pathway (i.e., thermal decomposition in solution, solvothermal method, dry thermal decomposition/calcination) or using a nonconventional energy source (i.e., microwave or ultrasonic treatment) to convert precursors into iron oxides. The resulting materials were structurally characterized by wide-angle X-ray diffraction and Fourier transform infrared, Raman, energy-dispersive X-ray, and X-ray fluorescence spectroscopies, as well as thermogravimetric analysis. The morphology was characterized by transmission electron microscopy, atomic force microscopy and dynamic light scattering. The parameters were varied within each route to fine tune the size and shape of the formed nanoparticles.

  5. Clinical efficacy and safety of a new 1000-mg suspension versus twice-daily 500-mg tablets of MPFF in patients with symptomatic chronic venous disorders: a randomized controlled trial.

    Carpentier, Patrick; van Bellen, Bonno; Karetova, Debora; Hanafiah, Harunarashid; Enriquez-Vega, Elizabeth; Kirienko, Alexander; Dzupina, Andrej; Sabovic, Miso; Reina Gutierrez, Lourdes; Subwongcharoen, Somboom; Tüzün, Hasan; Maggioli, Arnaud

    2017-10-01

    Chronic venous disorders (CVD) is estimated to affect 30% to 50% of women and 10% to 30% of men. The most widely prescribed treatment for CVD worldwide is micronized purified flavonoid fraction 500 mg (MPFF). The aim of this clinical trial was to develop a new once daily 1000-mg oral suspension of MPFF. In an international, randomized, double-blind, parallel-group study, symptomatic individuals classified CEAP C0s to C4s were randomized in either treatment arm and treated for 8 weeks. Lower limb symptoms (discomfort, pain and heaviness) were assessed using Visual Analog Scales (VAS), and quality of life (QoL) was measured with the CIVIQ-20 Questionnaire. A total of 1139 patients were included in the study. Both MPFF treatment regimens were well tolerated and associated with a significant reduction in lower limb symptoms. A non-inferiority of MPFF 1000-mg oral suspension once daily compared to MPFF 500-mg tablet twice daily (P1000 mg and -3.37 cm for MPFF 500 mg), leg pain (-3.27 cm for MPFF 1000 mg and -3.31 cm for MPFF 500 mg) and leg heaviness (-3.41 cm for MPFF 1000 mg and -3.46 cm for MPFF 500 mg). The patients' QoL was improved by about 20 points on the CIVIQ scale in both groups (19.33 points for MPFF 1000 mg and 20.28 points for MPFF 500 mg). MPFF 1000-mg oral suspension and MPFF 500-mg tablets treatments were associated with similar reductions in lower limb symptoms and QoL improvement. The new once daily MPFF1000-mg oral suspension has a similar safety profile to two tablets of MPFF 500 mg, with the advantage of one daily intake, potentially associated with improved patient adherence and easier CVD management.

  6. Efficacy of vildagliptin in combination with insulin in patients with type 2 diabetes and severe renal impairment

    Lukashevich, Valentina; Schweizer, Anja; Foley, James E; Dickinson, Sheila; Groop, Per-Henrik; Kothny, Wolfgang

    2013-01-01

    Background The purpose of this study was to evaluate the efficacy of vildagliptin 50 mg once daily in patients with severe renal impairment (estimated glomerular filtration rate vildagliptin 50 mg once daily versus placebo in patients with type 2 diabetes and moderate or severe renal impairment. The present data derive from 178 patients with severe renal impairment (baseline estimated glomerular filtration rate approximately 21 mL/min/1.73 m2, 100 randomized to vildagliptin, 78 randomized to placebo), all of whom were receiving insulin therapy (alone or in combination with an oral antidiabetic agent) for longstanding type 2 diabetes (mean approximately 19 years). Results With vildagliptin in combination with insulin, the adjusted mean change (AMΔ) in HbA1c from baseline (7.7% ± 0.1%) was −0.9% ± 0.4% and the between-treatment difference (vildagliptin – placebo) was −0.6% ± 0.2% (P vildagliptin than placebo (45.2% versus 22.8%, P = 0.008). When added to insulin, vildagliptin and placebo had comparable hypoglycemic profiles and did not cause weight gain. Both treatments were similarly well tolerated, with comparable incidences of adverse events, serious adverse events, and deaths. Conclusion When added to insulin therapy in patients with severe renal impairment and longstanding type 2 diabetes, vildagliptin 50 mg once daily was efficacious, eliciting HbA1c reductions consistent with those previously reported for a patient population with much more recent onset of type 2 diabetes and normal renal function, and had a hypoglycemic profile comparable with placebo. Accordingly, vildagliptin is a suitable treatment option for patients with advanced type 2 diabetes and impaired renal function who require insulin therapy and present a serious therapeutic challenge in clinical practice. PMID:23378769

  7. A Randomized Controlled Trial of Vildagliptin Versus Alogliptin: Effective Switch From Sitagliptin in Patients With Type 2 Diabetes.

    Shigematsu, Erina; Yamakawa, Tadashi; Oba, Mari S; Suzuki, Jun; Nagakura, Jo; Kadonosono, Kazuaki; Terauchi, Yasuo

    2017-07-01

    We investigated the effects of vildagliptin or alogliptin on blood glucose and hemoglobin A1c (HbA1c) in patients with type 2 diabetes inadequately controlled by sitagliptin. In a single-center open-label trial, 35 patients with inadequate glycemic control on sitagliptin therapy (50 mg once daily) were randomly switched to treatment with vildagliptin (50 mg twice daily) or alogliptin (25 mg once daily). After 12 weeks, patients who failed to achieve the target HbA1c level of vildagliptin or alogliptin treatment were switched to high-dose sitagliptin (100 mg once daily) and the effect on glycemic control was assessed. Vildagliptin did not significantly alter the mean plasma glucose level (175.5 ± 54.4 mg/dL vs. 179.1 ± 73.4 mg/dL) or HbA1c (8.01% vs. 8.02%) after 12 weeks. With alogliptin, mean plasma glucose increased from 175.4 ± 50.9 mg/dL to 195.3 ± 55.0 mg/dL after 12 weeks and HbA1c increased significantly from 8.0% to 8.3% (P vildagliptin to high-dose sitagliptin (100 mg daily), HbA1c was increased to 8.3%, but it was significantly (P vildagliptin group than the alogliptin group (P = 0.008), but the response rate (achieving the target HbA1c vildagliptin, alogliptin, and sitagliptin) were different, and the effects of vildagliptin and sitagliptin were stronger than that of alogliptin.

  8. Evaluation of a potential transporter-mediated drug interaction between rosuvastatin and pradigastat, a novel DGAT-1 inhibitor.

    Kulmatycki, Kenneth; Hanna, Imad; Meyers, Dan; Salunke, Atish; Movva, Aishwarya; Majumdar, Tapan; Natrillo, Adrienne; Vapurcuyan, Arpine; Rebello, Sam; Sunkara, Gangadhar; Chen, Jin

    2015-05-01

    An in vitro drugdrug interaction (DDI) study was performed to assess the potential for pradigastat to inhibit breast cancer resistance protein (BCRP), organic anion-transporting polypeptide (OATP), and organic anion transporter 3 (OAT3) transport activities. To understand the relevance of these in vitro findings, a clinical pharmacokinetic DDI study using rosuvastatin as a BCRP, OATP, and OAT3 probe substrate was conducted. The study used cell lines that stably expressed or over-expressed the respective transporters. The clinical study was an open-label, single sequence study where subjects (n = 36) received pradigastat (100 mg once daily x 3 days thereafter 40 mg once daily) and rosuvastatin (10 mg once daily), alone and in combination. Pradigastat inhibited BCRP-mediated efflux activity in a dose-dependent fashion in a BCRP over-expressing human ovarian cancer cell line with an IC(50) value of 5 μM. Similarly, pradigastat inhibited OATP1B1, OATP1B3 (estradiol 17β glucuronide transport), and OAT3 (estrone 3 sulfate transport) activity in a concentrationdependent manner with estimated IC(50) values of 1.66 ± 0.95 μM, 3.34 ± 0.64 μM, and 0.973 ± 0.11 μM, respectively. In the presence of steady state pradigastat concentrations, AUC(τ, ss) of rosuvastatin was unchanged and its Cmax,ss decreased by 14% (5.30 and 4.61 ng/mL when administered alone and coadministered with pradigastat, respectively). Pradigastat AUC(τ, ss) and C(max, ss) were unchanged when coadministered with rosuvastatin at steady state. Both rosuvastatin and pradigastat were well tolerated. These data indicate no clinically relevant pharmacokinetic interaction between pradigastat and rosuvastatin.

  9. Safety and efficacy of fimasartan in Mexican patients with grade 1-2 essential hypertension.

    Cardona-Muñoz, Ernesto G; López-Alvarado, Agustín; Conde-Carmona, Ignacio; Sánchez-Mejorada, Gerardo; Pascoe-González, Sara; Banda-Elizondo, Ramiro G; García-Castillo, Armando; González-Gálvez, Guillermo; Velasco-Sánchez, Raúl G; Vidrio-Velázquez, Maricela; Leiva-Pons, José L; Villeda-Espinosa, Efraín; Guerra-López, Arturo; Esturau-Santalo, Ramón M

    To evaluate efficacy and safety of 60mg and 120mg Fimasartan (FMS) alone or combined with 12.5mg hydrochlorothiazide (HCTZ) in a Mexican population. A six month, treat-to-target, open study was conducted on subjects with grade 1-2 hypertension. The subjects were initially treated with 60mg FMS once daily. In week 8, those with Diastolic Blood Pressure (DBP) <90mmHg continued on the same FMS dose during the rest of the study, while those with DBP ≥90mmHg were randomised to either 120mg FMS or 60mg FMS + 12.5mg HCTZ once daily. In week 12, randomised subjects with DBP ≥90mmHg received 120mg FMS+12.5mg HCTZ, while those achieving target continued with their assigned treatment until the end of the study. FMS 60mg (n=272) decreased both DBP and Systolic Blood Pressure (SBP) by 11.3±8.9 (p<.0001) and 16.0±14.1 (p<.0001)mmHg, respectively, with 75.4% of subjects reaching the treatment target. Subjects assigned to FMS 120mg, FMS 60mg+HCTZ 12.5mg, or FMS 120mg+HCTZ 12.5mg once daily, showed significant reductions in DBP and SBP with their assigned treatment. At the end of the study, 237/272 subjects (87.1%) achieved a DBP<90mmHg and an SBP<140mmHg. The most frequently reported adverse reactions included headache (3.7%), dry mouth (1.1%), transient liver enzyme increase (1.1%), and dizziness (0.7%). Fimasartan is safe and effective in Mexican subjects with grade 1-2 essential hypertension. Copyright © 2017 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  10. Whole-abdomen radiotherapy for non-Hodgkin's lymphoma using twice-daily fractionation

    Liauw, Stanley L.; Yeh, Alexander M.; Morris, Christopher G.; Olivier, Kenneth R.; Mendenhall, Nancy Price

    2006-01-01

    Purpose: To report the tolerability and efficacy of twice-daily whole-abdomen irradiation (WAI) for non-Hodgkin's lymphoma (NHL). Methods and Materials: Of 123 patients treated for NHL with WAI, 37% received previous chemotherapy, 28% received WAI as part of comprehensive lymphatic irradiation (CLI), and 32% received WAI for palliation. The median dose to the whole abdomen was 25.0 Gy, followed by a median tumor boost of 9.8 Gy in 58 patients. Fractionation was 1.0 Gy once daily (54%) or 0.8 Gy twice daily (46%). Blood counts were measured weekly. Results: At a median follow-up of 4.3 years, local control was 72% and overall survival was 55% at 5 years. Median time of WAI was 42 days for once-daily treatment and 32 days for twice-daily treatment. Patients receiving twice-daily WAI did not have a significantly higher rate of acute side effects (e.g., nausea, diarrhea, platelet or red blood cell toxicity). Overall, acute thrombocytopenia was the most frequent side effect of treatment; 24 of 96 patients (25%) with available hematologic data had Grade 3+ toxicity. There was no acute Grade 3 gastrointestinal toxicity and no late small bowel obstruction. Multiple regression indicated that patients with four or less involved sites and disease size ≤6 cm had improved local control and overall survival. Conclusions: Twice-daily WAI using 0.8 Gy/fraction does not appear to have any greater toxicity compared with once-daily treatment using 1 Gy/fraction. Small doses per fraction (0.8-1 Gy/fx) are effective, tolerated well in the acute setting, and associated with a low rate of late toxicity

  11. Post-marketing experience with nevirapine extended release (XR) tablets: effectiveness and tolerability in a population-based cohort in British Columbia, Canada.

    Lepik, Katherine J; Yip, Benita; McGovern, Rachel A; Ding, Erin; Nohpal, Adriana; Watson, Birgit E; Toy, Junine; Akagi, Linda; Harrigan, P Richard; Moore, David M; Hogg, Robert S; Montaner, Julio S G; Barrios, Rolando

    2015-01-01

    Nevirapine 400 mg extended release tablets (nevirapine-XR) are a once-daily alternative to nevirapine 200 mg immediate release tablets (nevirapine-IR). Study objectives were to describe the effectiveness and tolerability of nevirapine-XR in clinical practice and, for patients who switched from once daily 2×200 mg nevirapine-IR to nevirapine-XR, compare virological suppression and plasma nevirapine concentrations during each treatment period. HIV-1-infected adults entered the study cohort if they initiated nevirapine-XR in British Columbia (BC) Canada between 1 April 2012 and 30 September 2012 and were followed until 30 September 2013. Demographic and clinical variables were abstracted from the BC Centre for Excellence in HIV/AIDS databases. Patients who switched from once daily nevirapine-IR to nevirapine-XR were monitored for 6 months pre- and post-switch with comparison of virological suppression (McNeamer's test) and median random plasma nevirapine concentrations (Wilcoxon-Mann-Whitney test) in each period. The 536 nevirapine-XR-treated patients were 96% male, median (IQR) age 49.9 (44.0-56.9) years. Median follow-up was 15.6 (14.7-16.5) months, with 474/536 (88%) maintaining virological suppression. Emergent drug resistance developed in 5/536 (1%), adverse drug reactions in 17/536 (3%) and, although 31/536 (6%) reported 'whole' tablets in their stools, this was not associated with adverse outcomes. Among the 305 patients who switched from nevirapine-IR to nevirapine-XR, median (IQR) random plasma nevirapine concentration was higher during nevirapine-IR 5,000 (3,690-6,090) ng/ml than nevirapine-XR 3,930 (3,050-5,150) ng/ml (Pmarketing study affirms the effectiveness and tolerability of nevirapine-XR as an alternative to nevirapine-IR in adults.

  12. Psychometric validation of the Dutch translation of the quality of life in reflux and dyspepsia (QOLRAD questionnaire in patients with gastroesophageal reflux disease

    Engels Leopold GJB

    2010-08-01

    Full Text Available Abstract Background The Quality of Life in Reflux and Dyspepsia (QOLRAD questionnaire is one of the best-characterized disease-specific instruments that captures health-related problems and symptom-patterns in patients with gastroesophageal reflux disease (GERD. This paper reports the psychometric validation of a Dutch translation of the QOLRAD questionnaire in gastroenterology outpatients with GERD. Methods Patients completed the QOLRAD questionnaire at visit 1 (baseline, visit 2 (after 2, 4 or 8 weeks of acute treatment with esomeprazole 40 mg once daily, and visit 4 (after 6 months with on-demand esomeprazole 40 mg once daily or continuous esomeprazole 20 mg once daily. Symptoms were assessed at each visit, and patient satisfaction was assessed at visits 2 and 4. Results Of the 1166 patients entered in the study, 97.3% had moderate or severe heartburn and 55.5% had moderate or severe regurgitation at baseline. At visit 2, symptoms of heartburn and regurgitation were mild or absent in 96.7% and 97.7%, respectively, and 95.3% of patients reported being satisfied with the treatment. The internal consistency and reliability of the QOLRAD questionnaire (range: 0.83-0.92 supported construct validity. Convergent validity was moderate to low. Known-groups validity was confirmed by a negative correlation between the QOLRAD score and clinician-assessed severity of GERD symptoms. Effect sizes (1.15-1.93 and standardized response means (1.17-1.86 showed good responsiveness to change. GERD symptoms had a negative impact on patients' lives. Conclusions The psychometric characteristics of the Dutch translation of the QOLRAD questionnaire were found to be satisfactory, with good reliability and responsiveness to change, although convergent validity was at best moderate.

  13. Erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) combined responders to tadalafil after 12 weeks of treatment.

    Roehrborn, Claus G; Egan, Kathryn B; Miner, Martin M; Ni, Xiao; Wong, David G; Rosen, Raymond C

    2016-07-01

    To analyse the proportion of men taking tadalafil 5 mg once daily who experience a combined improvement in symptoms of both erectile dysfunction (ED) and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). The data from men aged ≥45 years randomized to tadalafil 5 mg once daily or placebo enrolled in one of four randomized, placebo-controlled LUTS/BPH clinical trials were analysed (N = 927). A novel classification of 'combined responders' to ED and LUTS/BPH treatment was defined, based on published criteria for men who showed improvement in both International Index of Erectile Function - Erectile Function domain (IIEF-EF) score and total International Prostate Symptom Score (IPSS). Descriptive analyses assessed the covariate distribution by responder status. Unadjusted and adjusted logistic regressions provided odds ratios with 95% confidence intervals comparing combined responders with all others (partial and non-responders). Among men randomized to tadalafil 5 mg, 40.5% were combined responders (n = 189). Among placebo randomized men, 18.3% were combined responders (n = 84). Combined responders, in the total population, had the highest baseline IPSS and lowest baseline IIEF-EF scores, corresponding to the highest level of dysfunction. The majority of men were aged ≤65 years, white, non-obese, non-smokers, and regular alcohol consumers. Only treatment, baseline IPSS, baseline IIEF-EF, obesity and psychoactive medication use were significantly associated with responder status (P ≤ 0.05). Tadalafil-treated men had 2.8 times significantly increased adjusted odds of being combined responders vs non-responders (P BPH after treatment with tadalafil 5 mg once daily vs placebo. This combined responder measure may be useful in future assessment of treatment benefits across patient groups after various types of treatment intervention (e.g. surgical vs pharmacotherapy vs non-pharmacological intervention). © 2016 The Authors BJU

  14. Comparative steady-state pharmacokinetic study of an extended-release formulation of itopride and its immediate-release reference formulation in healthy volunteers.

    Yoon, Seonghae; Lee, Howard; Kim, Tae-Eun; Lee, SeungHwan; Chee, Dong-Hyun; Cho, Joo-Youn; Yu, Kyung-Sang; Jang, In-Jin

    2014-01-01

    This study was conducted to compare the oral bioavailability of an itopride extended-release (ER) formulation with that of the reference immediate-release (IR) formulation in the fasting state. The effect of food on the bioavailability of itopride ER was also assessed. A single-center, open-label, randomized, multiple-dose, three-treatment, three-sequence, crossover study was performed in 24 healthy male subjects, aged 22-48 years, who randomly received one of the following treatments for 4 days in each period: itopride 150 mg ER once daily under fasting or fed conditions, or itopride 50 mg IR three times daily in the fasting state. Steady-state pharmacokinetic parameters of itopride, including peak plasma concentration (Cmax) and area under the plasma concentration versus time curve over 24 hours after dosing (AUC(0-24h)), were determined by noncompartmental analysis. The geometric mean ratio of the pharmacokinetic parameters was derived using an analysis of variance model. A total of 24 healthy Korean subjects participated, 23 of whom completed the study. The geometric mean ratio and its 90% confidence interval of once-daily ER itopride versus IR itopride three times a day for AUC(0-24h) were contained within the conventional bioequivalence range of 0.80-1.25 (0.94 [0.88-1.01]), although Cmax was reached more slowly and was lower for itopride ER than for the IR formulation. Food delayed the time taken to reach Cmax for itopride ER, but AUC(0-24h) was not affected. There were no serious adverse events and both formulations were generally well tolerated. At steady state, once-daily itopride ER at 150 mg has a bioavailability comparable with that of itopride IR at 50 mg given three times a day under fasting conditions. Food delayed the absorption of itopride ER, with no marked change in its oral bioavailability.

  15. Efficacy and tolerability of topical sertaconazole versus topical terbinafine in localized dermatophytosis: A randomized, observer-blind, parallel group study.

    Chatterjee, Dattatreyo; Ghosh, Sudip Kumar; Sen, Sukanta; Sarkar, Saswati; Hazra, Avijit; De, Radharaman

    2016-01-01

    Epidermal dermatophyte infections most commonly manifest as tinea corporis or tinea cruris. Topical azole antifungals are commonly used in their treatment but literature suggests that most require twice-daily application and provide lower cure rates than the allylamine antifungal terbinafine. We conducted a head-to-head comparison of the effectiveness of the once-daily topical azole, sertaconazole, with terbinafine in these infections. We conducted a randomized, observer-blind, parallel group study (Clinical Trial Registry India [CTRI]/2014/09/005029) with adult patients of either sex presenting with localized lesions. The clinical diagnosis was confirmed by potassium hydroxide smear microscopy of skin scrapings. After baseline assessment of erythema, scaling, and pruritus, patients applied either of the two study drugs once daily for 2 weeks. If clinical cure was not seen at 2 weeks, but improvement was noted, application was continued for further 2 weeks. Patients deemed to be clinical failure at 2 weeks were switched to oral antifungals. Overall 88 patients on sertaconazole and 91 on terbinafine were analyzed. At 2 weeks, the clinical cure rates were comparable at 77.27% (95% confidence interval [CI]: 68.52%-86.03%) for sertaconazole and 73.63% (95% CI 64.57%-82.68%) for terbinafine ( P = 0.606). Fourteen patients in either group improved and on further treatment showed complete healing by another 2 weeks. The final cure rate at 4 weeks was also comparable at 93.18% (95% CI 88.75%-97.62%) and 89.01% (95% CI 82.59%-95.44%), respectively ( P = 0.914). At 2 weeks, 6 (6.82%) sertaconazole and 10 (10.99%) terbinafine recipients were considered as "clinical failure." Tolerability of both preparations was excellent. Despite the limitations of an observer-blind study without microbiological support, the results suggest that once-daily topical sertaconazole is as effective as terbinafine in localized tinea infections.

  16. The H3 antagonist ABT-288 is tolerated at significantly higher exposures in subjects with schizophrenia than in healthy volunteers.

    Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Gertsik, Lev; Dutta, Sandeep

    2014-06-01

    ABT-288 is a potent and selective H3 receptor antagonist with procognitive effects in several preclinical models. In previous studies, 3 mg once daily was the maximal tolerated dose in healthy volunteers. This study characterized the safety, tolerability and pharmacokinetics of ABT-288 in stable subjects with schizophrenia. This was a randomized, double-blind, placebo-controlled, dose-escalating study of ABT-288 (10 dose levels, from 1 to 60 mg once daily for 14 days) in stable subjects with schizophrenia treated with an atypical antipsychotic. In each dose group, five to seven and two to three participants were assigned to ABT-288 and placebo, respectively. Of the 67 participants enrolled, nine participants (on ABT-288) were prematurely discontinued, in seven of these due to adverse events. ABT-288 was generally safe and tolerated at doses up to 45 mg once daily. The most common adverse events, in decreasing frequency (from 31 to 5%), were abnormal dreams, headache, insomnia, dizziness, somnolence, dysgeusia, dry mouth, psychotic disorder, parosmia and tachycardia. Adverse events causing early termination were psychotic events (four) and increased creatine phosphokinase, pyrexia and insomnia (one each). The half-life of ABT-288 ranged from 28 to 51 h, and steady state was achieved by day 12 of dosing. At comparable multiple doses, ABT-288 exposure in subjects with schizophrenia was 45% lower than that previously observed in healthy subjects. At trough, ABT-288 cerebrospinal fluid concentrations were 40% of the total plasma concentrations. ABT-288 was tolerated at a 15-fold higher dose and 12-fold higher exposures in subjects with schizophrenia than previously observed in healthy volunteers. The greater ABT-288 tolerability was not due to limited brain uptake. © 2013 The British Pharmacological Society.

  17. A randomized double-blinded placebo-controlled study to evaluate an effective ciclosporin dose for the treatment of feline hypersensitivity dermatitis.

    King, Stephen; Favrot, Claude; Messinger, Linda; Nuttall, Tim; Steffan, Jean; Forster, Sophie; Seewald, Wolfgang

    2012-10-01

    Hypersensitivity dermatitides (HD) are frequently suspected in cats, but there are few clinical studies on safe and effective treatments in the published literature. To establish a safe and effective dose of ciclosporin in the treatment of feline HD. One hundred client-owned cats with feline HD. Double-blind study, with cats randomly assigned to receive ciclosporin at either 7.0 mg/kg once daily (n = 33) or 2.5 mg/kg once daily (n = 32) or a placebo (n = 35) for 6 weeks. Mean Total Lesion Scores with 7.0 mg/kg ciclosporin were significantly lower than with 2.5 mg/kg ciclosporin (P = 0.0047) or placebo (P = 0.0003) at study end. Individual Total Lesion Scores improved by >50% in 70% of the 7.0 mg/kg group, compared with 47% in the 2.5 mg/kg group and 23% in the placebo group (P = 0.0006). The investigators' Global Assessment of Improvement was 'excellent' or 'good' in 61% of cats treated with 7.0 mg/kg ciclosporin, compared with 47% of cats given 2.5 mg/kg and 23% given placebo. The improvement in Investigator Pruritus Scores was significantly greater in cats treated with 7.0 mg/kg ciclosporin (54%) compared with both 2.5 mg/kg ciclosporin (32%; P = 0.0232) and placebo (21%; P = 0.0063). Mild gastrointestinal disorders were the most common adverse events, but these did not require cessation of therapy. Results suggest that 7.0 mg/kg ciclosporin once daily in food or per os for 6 weeks is effective and well tolerated in feline HD. © 2012 The Authors. Veterinary Dermatology © 2012 ESVD and ACVD.

  18. Vulvovaginitis and balanitis in patients with diabetes treated with dapagliflozin.

    Johnsson, Kristina M; Ptaszynska, Agata; Schmitz, Bridget; Sugg, Jennifer; Parikh, Shamik J; List, James F

    2013-01-01

    Vulvovaginitis, balanitis, and related genital infections are common in patients with type 2 diabetes. Glucosuria, which is an outcome of treatment with sodium glucose cotransporter 2 (SGLT2) inhibitors, is among the possible causes. Dapagliflozin, an SGLT2 inhibitor with demonstrated glycemic benefits in patients with diabetes, has been studied across a broad spectrum of patients. Analysis of multi-trial safety data may better define the relationship between glucosuria and genital infection. Safety data were pooled from 12 randomized, placebo-controlled Phase 2b/3 trials to analyze the association of glucosuria with genital infection in patients with suboptimally controlled diabetes (HbA1c >6.5%-12%). Patients were randomized to receive dapagliflozin (2.5mg, 5mg, or 10mg) or placebo once daily, either as monotherapy or add-on to metformin, insulin, sulfonylurea, or thiazolidinedione for 12-24weeks. The incidence of clinical diagnoses and of events suggestive of genital infection was evaluated. The pooled safety data included 4545 patients: 3152 who received once-daily dapagliflozin (2.5mg [n=814], 5mg [n=1145], or 10mg [n=1193]) as monotherapy or add-on treatment, and 1393 placebo-treated patients. For dapagliflozin 2.5mg, 5mg, 10mg, and placebo, diagnosed infections were reported in 4.1%, 5.7%, 4.8%, and 0.9%, respectively. Most infections were mild or moderate and responded to standard antimicrobial treatment. Discontinuation due to these events was rare. No clear dose-response relationship between dapagliflozin and genital infection was demonstrated. Treatment with dapagliflozin 2.5mg, 5mg, or 10mg once daily is accompanied by an increased risk of vulvovaginitis or balanitis, related to the induction of glucosuria. Events were generally mild to moderate, clinically manageable, and rarely led to discontinuation of treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Evaluation of the safety and efficacy of an edoxaban-based antithrombotic regimen in patients with atrial fibrillation following successful percutaneous coronary intervention (PCI) with stent placement: Rationale and design of the ENTRUST-AF PCI trial.

    Vranckx, Pascal; Lewalter, Thorsten; Valgimigli, Marco; Tijssen, Jan G; Reimitz, Paul-Egbert; Eckardt, Lars; Lanz, Hans-Joachim; Zierhut, Wolfgang; Smolnik, Rüdiger; Goette, Andreas

    2018-02-01

    The optimal antithrombotic treatment after percutaneous coronary intervention (PCI) with stenting in patients with atrial fibrillation (AF) is unknown. In the ENGAGE AF-TIMI 48 trial, edoxaban was noninferior to a vitamin K antagonist (VKA) with respect to the prevention of stroke or systemic embolism and was associated with significantly lower rates of bleeding and cardiovascular death in patients with nonvalvular AF. The effects of edoxaban in combination with single- or dual-antiplatelet therapy in the setting of PCI are unexplored. The ENTRUST-AF PCI trial is a multinational, multicenter, randomized, open-label phase 3b trial with blinded end point evaluation involving 1,500 patients on oral anticoagulation for AF. Patients are randomized between 4 hours and 5 days after successful PCI to either an edoxaban-based strategy (experimental arm; 60 mg [or 30 mg according to dose reduction criteria] once daily plus a P2Y 12 antagonist [default clopidogrel, 75 mg once daily] for 12 months) or a VKA-based strategy (control arm; VKA plus a P2Y 12 antagonist [as above] plus acetylsalicylic acid [100 mg once daily] for 30 days to 12 months). The primary safety end point is the incidence of International Society on Thrombosis and Haemostasis-defined major or clinically relevant nonmajor bleeding. The main efficacy end point is the composite of cardiovascular death, stroke, systemic embolic events, spontaneous myocardial infarction, and definite stent thrombosis. The ENTRUST-AF PCI trial tests the hypothesis that an edoxaban-based antithrombotic strategy reduces the risk of bleeding complications after PCI compared with VKA plus conventional dual-antiplatelet therapy in patients with AF in need of oral anticoagulation. The relative risk of ischemic events between groups will be compared. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Effect of darapladib on major coronary events after an acute coronary syndrome

    O'Donoghue, Michelle L; Braunwald, Eugene; White, Harvey D

    2014-01-01

    ]) at 868 sites in 36 countries. INTERVENTIONS: Patients were randomized to either once-daily darapladib (160 mg) or placebo on a background of guideline-recommended therapy. Patients were followed up for a median of 2.5 years between December 7, 2009, and December 6, 2013. MAIN OUTCOMES AND MEASURES......: The primary end point (major coronary events) was the composite of coronary heart disease (CHD) death, MI, or urgent coronary revascularization for myocardial ischemia. Kaplan-Meier event rates are reported at 3 years. RESULTS: During a median duration of 2.5 years, the primary end point occurred in 903...

  1. Fusarium solani breast abscess

    Anandi V

    2005-01-01

    Full Text Available An unusual manifestation of breast fusariosis was encountered in a 55-year-old female diabetic patient. Two fine needle aspirates (FNA from the abscess were done at three days interval and they showed hyaline, septate, branched, fungal hypahe in 10% potassium hydroxide mount. Fungal infection was confirmed by demonstrating the fungal hyphae in the midst of lymphocytes, macrophages and neutrophils in Leishman stained smears. Culture of both FNAs yielded a heavy and pure growth of Fusarium solani . The patient responded to oral ketoconazole 200 mg once daily for 3 weeks. The breast fusariosis reported here is presumably the first case in India.

  2. SPONTANEOUS SPLENIC RUPTURE SECONDARY TO RIVAROXABAN: RARE BUT RAISING

    Zainab Naseem

    2016-08-01

    Full Text Available A 68-year old male presented to our hospital with sudden onset of left sided chest and abdominal pain. The patient was previously treated for left lower lobe pneumonia and reported no history of chest or abdominal trauma. His medical history included atrial fibrillation which was managed by rivaroxaban 20 mg once daily. Computed tomography of the abdomen demonstrated a splenic haematoma. The patient rapidly deteriorated and developed hypovolaemic shock. Emergency laparotomy revealed haemoperitoneum of 3500 mL and the ruptured spleen. The postoperative course was complicated by pancreatic fistula formation which eventually resolved.

  3. New Horizons in Allergen Immunotherapy

    Backer, Vibeke

    2016-01-01

    . The authors concluded that among adultswithHDMallergy–related asthma not well controlled by ICS, the addition of HDM SLIT deliveredas a once-daily tablet significantly prolongedthetime to the first asthma exacerbation during ICS reduction. Aswith any clinical trial, the critical question is howmeaningful...... the active therapycomparedwith placebowhendifferent criteriawere used todefine asthma exacerbations, aswell as in immunologic changes consistentwith desensitization.However, therewerenosignificantdifferences inpatients’ responses toquestionnairesregardingeitherasthmacontrolorqualityoflife. The authors...... treatmentwith ICS. The authors’ choice of a primary end point based on exacerbations during ICS reduction is also unique to immunotherapy trials,with previous trials ofHDMimmunotherapy focusing onmedication requirements, symptomsscores, or lung function as primary end points. Furthermore, the inclusion...

  4. The use of rasagiline in Parkinson's disease.

    Schapira, A H V

    2006-01-01

    Rasagiline is a novel, potent, irreversible inhibitor of monoamine oxidative B developed for the symptomatic treatment of Parkinson's disease. The drug has shown efficacy in improving motor features in both early and advanced Parkinson's disease patients. The drug appears to be well tolerated and its once daily fixed dose formulation should make for excellent compliance. Rasagiline has also demonstrated important neuroprotective properties in both in vitro and in vivo laboratory studies. A provisional study of neuroprotection in a delayed start clinical trial of early PD patients has also suggested that this benefit may be translated to the clinic. Additional clinical trials are underway to confirm this.

  5. Successful management of refractory cases of canine demodicosis with homeopathy medicine Graphitis.

    Ranjan, Rakesh; Dua, Kirti; Turkar, Sujata; Singh, Harkirat; Singla, L D

    2014-12-01

    Canine demodicosis is a refractory skin disease caused by excessive proliferation of mite Demodex canis. Despite availability of several treatment options, the disease poses a great challenge to clinicians for its long term management as some drugs may be ineffective or toxic. Present report describes successful treatment of two refractory cases of canine demodicosis using homeopathy medicine. After oral administration of Graphitis 200 C two drops once daily for 2 months, complete cure from the disease was observed. No adverse health effects of the medication were recorded during the treatment. Thus, it may be concluded that homeopathy medicine may be used safely for long-term management of canine demodicosis.

  6. Immunoglobulin G for patients with necrotising soft tissue infection (INSTINCT)

    Madsen, Martin B.; Hjortrup, Peter B.; Hansen, Marco B.

    2017-01-01

    Purpose: The aim of the INSTINCT trial was to assess the effect of intravenous polyspecific immunoglobulin G (IVIG) compared with placebo on self-reported physical function in intensive care unit (ICU) patients with necrotising soft tissue infection (NSTI). Methods: We randomised 100 patients...... with NSTI 1:1 to masked infusion of 25 g of IVIG (Privigen, CSL Behring) or an equal volume of 0.9% saline once daily for the first 3 days of ICU admission. The primary outcome was the physical component summary (PCS) score of the 36-item short form health survey (SF-36) 6 months after randomisation...

  7. Saxagliptin: a new dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes

    Deacon, Carolyn F; Holst, Jens J

    2009-01-01

    Saxagliptin is a potent and selective reversible inhibitor of dipeptidyl peptidase-4, which is being developed for the treatment of type 2 diabetes. It is absorbed rapidly after oral administration and has a pharmacokinetic profile compatible with once daily dosing. Saxagliptin is metabolized...... a neutral effect on body weight and dose adjustment because of age, gender, or hepatic impairment is not necessary. Saxagliptin is being co-developed by Bristol-Myers-Squibb (New York, NY, USA) and AstraZeneca (Cheshire, UK), and is currently undergoing regulatory review....

  8. Successful management of stuttering priapism using home self-injections of the alpha-agonist metaraminol

    Mcdonald Michael

    2004-01-01

    Full Text Available Low-flow priapism can result in impotence if treatment is delayed, yet patients with recurrent priapism often suffer delay before therapy. We describe management of recurrent priapism using self-administered injections of intracavernosal metaraminol (Aramine™, Merck, a long-acting vasoconstricting amine that is considered safer than epinephrine. The patient injects as often as once daily using 5-10 mg of drug. Our patient reports rapid detumescence and has not required emergency room visits since starting injections. He denies complications. Treatment of priapism using metaraminol has been suggested in the hospital setting; however, this is the first report of successful home self-administration of the drug.

  9. Escitalopram in painful polyneuropathy: A randomized, placebo-controlled, cross-over trial

    Otto, Marit; Bach, Flemming W; Jensen, Troels S

    2008-01-01

    Serotonin (5-HT) is involved in pain modulation via descending pathways in the central nervous system. The aim of this study was to test if escitalopram, a selective serotonin reuptake inhibitor (SSRI), would relieve pain in polyneuropathy. The study design was a randomized, double-blind, placebo......-controlled cross-over trial. The daily dose of escitalopram was 20mg once daily. During the two treatment periods of 5 weeks duration, patients rated pain relief (primary outcome variable) on a 6-point ordered nominal scale. Secondary outcome measures comprised total pain and different pain symptoms (touch...

  10. Treatment of type 2 diabetes mellitus with agonists of the GLP-1 receptor or DPP-IV inhibitors

    Holst, Jens Juul

    2004-01-01

    in the treatment of Type 2 diabetes, causing marked improvements in glycaemic profile, insulin sensitivity and beta-cell performance, as well as weight reduction. The hormone is metabolised rapidly by the enzyme dipeptidyl peptidase IV (DPP-IV) and, therefore, cannot be easily used clinically. Instead, resistant...... with exendin have been carried out for > 6 months and have indicated efficacy in patients inadequately treated with oral antidiabetic agents. Orally active DPP-IV inhibitors, suitable for once-daily administration, have demonstrated similar efficacy. Diabetes therapy, based on GLP-1 receptor activation...

  11. Comparison of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment: a randomised clinical trial.

    Kothny, Wolfgang; Lukashevich, Valentina; Foley, James E; Rendell, Marc S; Schweizer, Anja

    2015-09-01

    There are limited data comparing dipeptidyl peptidase-4 (DPP-4) inhibitors directly. We compared the safety and efficacy of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment (RI). This study was a parallel-arm, randomised, multicentre, double-blind, 24 week study conducted in 87 centres across Brazil and the USA. Patients with type 2 diabetes, either drug naive or treated with any glucose-lowering agents, who had inadequate glycaemic control (HbA1c 6.5-10.0% [48-86 mmol/mol]) and an estimated GFR vildagliptin 50 mg once daily or sitagliptin 25 mg once daily. These doses are recommended in this patient population and considered maximally effective. Participants, investigators and the sponsor were blinded to group assignment. Efficacy endpoints included change in HbA1c and fasting plasma glucose (FPG) at all visits and the primary safety endpoint was assessment of treatment-emergent adverse events. In total, 148 patients were randomised, 83 to vildagliptin and 65 to sitagliptin. All patients were analysed. After 24 weeks, the adjusted mean change in HbA1c was -0.54% (5.9 mmol/mol) from a baseline of 7.52% (59 mmol/mol) with vildagliptin and -0.56% (6.1 mmol/mol) from a baseline of 7.80% (62 mmol/mol) with sitagliptin (p = 0.874). FPG decreased by 0.47 ± 0.37 mmol/l with vildagliptin and increased by 0.16 ± 0.43 mmol/l with sitagliptin (p = 0.185). Both treatments were well tolerated with overall similar safety profiles. At their recommended doses for severe RI, vildagliptin (50 mg once daily) compared with sitagliptin (25 mg once daily) demonstrated similar efficacy and both drugs were well tolerated. This study provides further support for the use of DPP-4 inhibitors in patients with severe RI. ClinicalTrials.gov NCT00616811 (completed) This study was planned and conducted by Novartis.

  12. Effect of repeated oral administration of bifenthrin on lipid peroxidation and anti-oxidant parameters in Wistar rats.

    Dar, Muneer Ahmad; Khan, Adil Mehraj; Raina, Rajinder; Verma, Pawan Kumar; Sultana, Mudasir

    2013-07-01

    The oxidative stress-inducing potential of the pyrethroid insecticide, bifenthrin, was evaluated in rats at 5.8 mg/kg body weight once daily for 20 or 30 days. Bifenthrin treated animals showed significantly increased lipid peroxidation, evidenced by increased blood malondialdehyde levels. Blood glutathione levels and activities of catalase and glutathione peroxidase decreased significantly in the bifenthrin treated animals after both 20 and 30 days of treatment, whereas, the activities of superoxide dismutase and glutathione S-transferase decreased significantly only on the 30th day. In conclusion, bifenthrin has a potential to induce severe oxidative stress in rats exposed to sublethal concentrations.

  13. IDegLira Versus Alternative Intensification Strategies in Patients with Type 2 Diabetes Inadequately Controlled on Basal Insulin Therapy

    Freemantle, Nick; Mamdani, Muhammad; Vilsbøll, Tina

    2015-01-01

    INTRODUCTION: IDegLira is a once-daily combination of insulin degludec (IDeg) and liraglutide. Trials directly comparing IDegLira with alternative strategies for intensifying basal insulin are ongoing. While awaiting results, this analysis compared indirectly how different strategies affected......Lira versus up-titrated IGlar. The supplementary analysis yielded similar results to the main analysis. Results with IDegLira were similar to those for the 'GLP-1RA add-on' arm. CONCLUSION: These results suggest that IDegLira may be more effective, with lower hypoglycemia rates and less weight gain, than up...

  14. Randomised study of Casodex 50 MG monotherapy vs orchidectomy in the treatment of metastatic prostate cancer. The Scandinavian Casodex Cooperative Group

    Iversen, P; Tveter, K; Varenhorst, E

    1996-01-01

    The effect of Casodex (ICI 176,334), a new, once-daily, selective antiandrogen, given as 50 mg monotherapy, was compared with orchidectomy in a randomised, multicentre, open study in 376 patients with metastatic prostate cancer. At 3 months, PSA was reduced by 86% in the Casodex group and by 96......% in the orchidectomy group. Treatment failed in 51 patients in the orchidectomy group and 66 showed a subjective response. Treatment failed in 86 patients treated with Casodex and 40 patients showed a subjective response. Patients treated with Casodex maintained their sexual interest better than those...

  15. A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease

    Filippatos, Gerasimos; Anker, Stefan D; Böhm, Michael

    2016-01-01

    Aims To evaluate oral doses of the non-steroidal mineralocorticoid receptor antagonist finerenone given for 90 days in patients with worsening heart failure and reduced ejection fraction and chronic kidney disease and/or diabetes mellitus. Methods and results Miner Alocorticoid Receptor antagonist...... Tolerability Study-Heart Failure (ARTS-HF) was a randomized, double-blind, phase 2b multicentre study (ClinicalTrials.gov: NCT01807221). Of 1286 screened patients, 1066 were randomized. Patients received oral, once-daily finerenone (2.5, 5, 7.5, 10, or 15 mg, uptitrated to 5, 10, 15, 20, or 20 mg, respectively...

  16. Efficacy and safety of extended-release oxcarbazepine (Oxtellar XR™) as adjunctive therapy in patients with refractory partial-onset seizures: a randomized controlled trial

    French, JA; Baroldi, P; Brittain, ST; Johnson, JK

    2014-01-01

    Objective To evaluate the efficacy, tolerability, and safety of once-daily 1200 mg and 2400 mg SPN-804 (Oxtellar XR™, Supernus Pharmaceuticals), an extended-release tablet formulation of oxcarbazepine (OXC), added to 1-3 concomitant antiepileptic drugs (AEDs) in adults with refractory partial-onset seizures, with or without secondary generalization. Methods The Prospective, Randomized Study of OXC XR in Subjects with Partial Epilepsy Refractory (PROSPER) study was a multinational, randomized, double-blind, parallel-group Phase 3 study. The primary efficacy endpoint was median percent reduction from baseline in monthly (28-day) seizure frequency for the 16-week double-blind treatment period in the intent-to-treat (ITT) population with analyzable seizure data. Other efficacy analyses included proportion of patients with ≥ 50% seizure reduction, proportion of patients seizure free, and the relationship between clinical response and plasma concentration. Results Median percent reduction was -28.7% for placebo, −38.2% (P = 0.08 vs placebo) for once-daily SPN-804 1200 mg, and −42.9% (P = 0.003) for SPN-804 2400 mg. Responder rates were 28.1%, 36.1% (P = 0.08), and 40.7% (P = 0.02); 16-week seizure-free rates in a pragmatic ITT analysis were 3.3%, 4.9% (P = 0.59), and 11.4% (P = 0.008), respectively. When data were analyzed separately for study site clusters, a post hoc analysis demonstrated that both SPN-804 dosages were significantly superior to placebo in median percent seizure reduction (placebo: −13.3%; 1200 mg: −34.5%, P = 0.02; 2400 mg: −52.7%, P = 0.006) in the North American study site cluster. A concentration–response analysis also supported a clinically meaningful effect for 1200 mg. Adverse event types reflected the drug's established profile. Adverse event frequency was consistent with a pharmacokinetic profile in which SPN-804 produces lower peak plasma concentrations vs immediate-release OXC. Once-daily dosing was not

  17. Lack of interaction between a new antihistamine, mizolastine, and lorazepam on psychomotor performance and memory in healthy volunteers.

    Patat, A; Perault, M C; Vandel, B; Ulliac, N; Zieleniuk, I; Rosenzweig, P

    1995-01-01

    1. The possible interaction between a new H1 antihistamine, mizolastine, and lorazepam was assessed in a randomised, double-blind, cross-over, placebo-controlled study involving 16 healthy young male volunteers who received mizolastine 10 mg or placebo once daily for 8 days with a 1 week wash-out interval. The interaction of mizolastine, at steady-state, with a single oral dose of lorazepam or placebo was assessed on days 6 or 8 of each treatment period. 2. Psychomotor performance and cogniti...

  18. Powerful vascular protection by combining cilnidipine with valsartan in stroke-prone, spontaneously hypertensive rats

    Takai, Shinji; Jin, Denan; Aritomi, Shizuka; Niinuma, Kazumi; Miyazaki, Mizuo

    2012-01-01

    Cilnidipine is an L- and N-type calcium channel blocker (CCB), and amlodipine is an L-type CCB. Valsartan (10?mg?kg?1), valsartan (10?mg?kg?1) and amlodipine (1?mg kg?1), and valsartan (10?mg?kg?1) and cilnidipine (1?mg?kg?1) were administered once daily for 2 weeks to stroke-prone, spontaneously hypertensive rats (SHR-SPs). Blood pressure was significantly reduced by valsartan, and it was further reduced by the combination therapies. Vascular endothelial dysfunction was significantly attenua...

  19. [Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy].

    Pesić, Milica; Zivić, Sasa; Radenković, Sasa; Velojić, Milena; Dimić, Dragan; Antić, Slobodan

    2007-04-01

    Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin) for basal insulin supply in patients with type 1 diabetes. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IT) were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15); 2. NPH insulin twice daily (n = 15); 3. insulin glargine once daily (n = 18). Meal time insulin aspart was continued in all groups. Fasting blood glucose (FBG) was lower in the glargine group (7.30+/-0.98 mmol/1) than in the twice daily NPH group (7.47+/-1.06 mmol/1), but without significant difference. FBG was significantly higher in the once daily NPH group (8.44+/-0.85 mmol/l; p < 0.05). HbAlc after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72+/-0.86% to 6.87+/-0.50%), as well as in the twice daily NPH group (from 7.80+/-0.83% to 7.01+/-0.63%). Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56+/-2.09) than in both NPH groups (9.0+/-1.65 in twice daily NPH group and 8.13+/-1.30 in other NPH group) (episodes/patients-month, p < 0.05). Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbAlc and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

  20. Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy

    Pešić Milica

    2007-01-01

    Full Text Available Background/Aim. Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin for basal insulin supply in patients with type 1 diabetes. Methods. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IIT were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15; 2. NPH insulin twice daily (n = 15; 3. insulin glargine once daily (n = 18. Meal time insulin aspart was continued in all groups. Results. Fasting blood glucose (FBG was lower in the glargine group (7.30±0.98 mmol/l than in the twice daily NPH group (7.47±1.06 mmol/l, but without significant difference. FBG was significantly higher in the once daily NPH group (8.44±0.85 mmol/l; p < 0.05. HbA1c after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72±0.86% to 6.87±0.50%, as well as in the twice daily NPH group (from 7.80±0.83% to 7.01±0.63%. Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56±2.09 than in both NPH groups (9.0±1.65 in twice daily NPH group and 8.13±1.30 in other NPH group (episodes/patients-month, p < 0.05. Conclusion. Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbA1c and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

  1. Kidney graft rejection studies with labeled platelets and lymphocytes

    Martin-Comin, J.

    1986-01-01

    The usefulness of In-111-labelled platelets and lymphocyte scintigraphy in acute kidney graft rejection is evaluated in 155 patients. Blood cells were labelled with 100-150 uCi of In-111-oxine and reinjected. Subsequently patients were scanned once daily from 2 hours post-reinjection up to a week. The graft/contralateral area activity ratio was calculated in all scans. It is concluded that In-111-labelled platelets scintigraphy is nowadays the method of choice for acute kidney graft rejection diagnosis, especially in patients under cyclosporine immunosuppression. (author)

  2. The Possible Protective Role of Green Tea against Radiation induced Certain Biochemical and Trace Element Changes in Rats

    Hanna, M.M.A.

    2012-01-01

    The process of ionization occurring after radiation energy absorption in atoms and molecules of biological matter results in biochemical alterations, which cause damage to cellular elements. This damage is mediated through generation of reactive oxygen species (ROS) that in turn damage proteins, lipids, nucleic-acids and trace elements. They also can attack poly unsaturated fatty acids and initiate lipid peroxidation within the cell. So the present study was constructed in order to assess the role of green tea extract (GTE) (300 mg/kg) to overcome the hazards of ionizing radiation. The parameters studied in the current work were serum AST, ALT and ALP activities as well as serum levels of cholesterol, triglyceride, urea and creatinine. Liver and kidney glutathione (GSH), lipid peroxidation (TBARS) and metallothioneins (MTs) contents were also investigated. In addition, contents of some trace elements (Fe, Cu, Zn, Ca, Mg, Se and Mn) in liver, kidney, spleen and testis tissues as well as the content of these trace elements in green tea plant and green tea extract were also estimated. Vitamin E was selected and used at dose of 40 mg/kg as reference standard. Male Wistar albino rats (48) were used, weighing 120-150 g, divided into 6 groups, each consists of 8 rats: Group (1) → received saline for 28 days and served as normal group, Group (2) → received GTE once daily for 28 days, Group (3) → received vitamin E once daily for 28 days, Group 4 → received saline for 21 days then were exposed to 6.5 Gy single dose whole body gamma irradiation followed by receiving saline for 7 days later and served as irradiated control, Group (5) → received GTE once daily for 21 days, and then were exposed to single dose whole body gamma irradiation (6.5 Gy), followed by treatment with GTE 7 days later to be 28 days as group 2 and Group (6) → received vitamin E once daily for 21 days, and then were exposed to single dose whole body gamma irradiation (6.5 Gy), followed by

  3. Vitamin D and Risk for Vitamin A Intoxication in an 18-Month-Old Boy

    Talarico, Valentina; Barreca, Massimo; Galiano, Rossella; Galati, Maria Concetta; Raiola, Giuseppe

    2016-01-01

    An 18-month-old boy presented with abdominal pain, vomiting, diarrhea, and poor appetite for 6 days. He had been given a multivitamin preparation once daily, containing 50.000 IU of vitamin D and 10.000 IU of vitamin A for a wide anterior fontanelle for about three months. He presented with hypercalcemia, low levels of parathyroid hormone (PTH), and very high serum 25-hydroxyvitamin D (25-OHD) levels. Renal ultrasound showed nephrocalcinosis. He did not have sign or symptom of vitamin A intox...

  4. Liraglutide Treatment Is Associated with a Low Frequency and Magnitude of Antibody Formation with No Apparent Impact on Glycemic Response or Increased Frequency of Adverse Events

    Buse, John B; Garber, Alan; Rosenstock, Julio

    2011-01-01

    the impact on glycemic control and safety, and to compare it with exenatide, an agent in the same class. Design: Antibody data were collected during six Liraglutide Effect and Action in Diabetes (LEAD) trials (26–104 wk duration). Setting: Samples for determination of antibody formation were collected...... at LEAD trial sites and analyzed at central laboratories. Participants: Antibodies were measured in LEAD trial participants with type 2 diabetes. Interventions: Interventions included once-daily liraglutide (1.2 or 1.8 mg) or twice-daily exenatide (10 µg). Main Outcome Measures: The main outcome measures...... not impact glycemic efficacy or safety....

  5. The GLP-1 analogue liraglutide improves first-phase insulin secretion and maximal beta-cell secretory capacity over 14 weeks of therapy in subjects with Type 2 diabetes

    Madsbad, Sten; Vilsbøll, Tina; Brock, Birgitte

    Aims: We investigated the clinical effect of liraglutide, a long- acting GLP-1 analogue, on insulin secretion in Type 2 diabetes. Methods: Thirty-nine subjects (28 completed) from a randomised trial received a hyperglycaemic clamp (20 mM) with intravenous arginine stimulation, and an insulin...... group. Conclusion: In subjects with Type 2 diabetes, 14 weeks’ once-daily liraglutide (1.25 and 1.9 mg/day) markedly improves beta-cell function, significantly increases first-phase insulin secretion and maximal beta-cell secretory capacity....

  6. Effects of a hot-water extract of porcini (Boletus aestivalis) mushrooms on the blood pressure and heart rate of spontaneously hypertensive rats.

    Midoh, Naoki; Miyazawa, Noriko; Eguchi, Fumio

    2013-01-01

    The repeated once-daily oral administration of a hot-water extract of porcini, Boletus aestivalis, mushrooms (WEP) to spontaneously hypertensive rats (SHR) for 18 weeks decreased the systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate. The WEP administration also decreased blood urea nitrogen (BUN), creatinine (Cre), and triglyceride (TG), and increased high-density lipoprotein-cholesterol (HDL-C) in the blood, suggesting that WEP improved the status of hypertension, as well as the high heart rate and metabolic abnormalities involved in hypertension.

  7. Delayed Treatment of Ebola Virus Infection with Plant-Derived Monoclonal Antibodies Provides Protection in Rhesus Macaques

    2012-10-15

    filtration (Mustang Q membrane ; Pall). The final polishing column for c13C6 and c6D8 was a CHT, Type I 40-μm (Bio-Rad) column. The columnwas...monkey chow, primate treats, fruits, and vegetables throughout the course of the study. Animals were observed at least once daily to monitor overall...Coulter Act 10 (Beckman Coulter) on samples collected in EDTA plasma vacuette tubes (Greiner Bio-One). Blood was collected in 2-mL serum vacuette tubes

  8. Pharmacokinetic Effects of Isavuconazole Coadministration With the Cytochrome P450 Enzyme Substrates Bupropion, Repaglinide, Caffeine, Dextromethorphan, and Methadone in Healthy Subjects

    Yamazaki, Takao; Desai, Amit; Goldwater, Ronald; Han, David; Howieson, Corrie; Akhtar, Shahzad; Kowalski, Donna; Lademacher, Christopher; Pearlman, Helene; Rammelsberg, Diane; Townsend, Robert

    2016-01-01

    Abstract This report describes phase 1 clinical trials performed to assess interactions of oral isavuconazole at the clinically targeted dose (200 mg, administered as isavuconazonium sulfate 372 mg, 3 times a day for 2 days; 200 mg once daily [QD] thereafter) with single oral doses of the cytochrome P450 (CYP) substrates: bupropion hydrochloride (CYP2B6; 100?mg; n = 24), repaglinide (CYP2C8/CYP3A4; 0.5 mg; n = 24), caffeine (CYP1A2; 200 mg; n = 24), dextromethorphan hydrobromide (CYP2D6/CYP3A...

  9. FDA approves efavirenz. Food and Drug Administration.

    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.

  10. Withdrawal of inhaled glucocorticoids and exacerbations of COPD

    Magnussen, Helgo; Disse, Bernd; Rodriguez-Roisin, Roberto

    2014-01-01

    fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric......-acting bronchodilators has not been fully explored. METHODS: In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid...

  11. Nefopam hydrochloride loaded microspheres for post-operative pain management: synthesis, physicochemical characterization and in-vivo evaluation.

    Sharma, Neelam; Arora, Sandeep; Madan, Jitender

    2018-02-01

    Once-daily oral dosage of nefopam hydrochloride loaded sustained release microspheres (NPH-MS) was investigated as novel therapeutic strategy for post-operative pain management. Microspheres were synthesized using poly-3-hydroxybutyrate and poly-(ɛ-caprolactone) by double emulsion solvent evaporation technique. NPH-MS were characterized through FTIR, PXRD and SEM. In-vitro drug release study revealed sustained behavior till 24 h. Haemolysis was pain model, reversal of mechanical allodynia and thermal hyperalgesia by NPH-MS was statistically significant (p < .001) as compared with NPH till 24 h post-dose.

  12. Polaprezinc reduces paclitaxel-induced peripheral neuropathy in rats without affecting anti-tumor activity

    Kuniaki Tsutsumi; Takanori Kaname; Haruka Shiraishi; Takehiro Kawashiri; Nobuaki Egashira

    2016-01-01

    Paclitaxel, an anticancer drug, frequently causes painful peripheral neuropathy. In this study, we investigated the preventive effect of polaprezinc on paclitaxel-induced peripheral neuropathy in rats. Polaprezinc (3 mg/kg, p.o., once daily) inhibited the development of mechanical allodynia induced by paclitaxel (4 mg/kg, i.p., on days 1, 3, 5 and 7) and suppressed the paclitaxel-induced increase in macrophage migration in dorsal root ganglion cells. In addition, polaprezinc did not affect th...

  13. Safety, tolerability and pharmacokinetics of doravirine, a novel HIV non-nucleoside reverse transcriptase inhibitor, after single and multiple doses in healthy subjects.

    Anderson, Matt S; Gilmartin, Jocelyn; Cilissen, Caroline; De Lepeleire, Inge; Van Bortel, Luc; Dockendorf, Marissa F; Tetteh, Ernestina; Ancona, June K; Liu, Rachael; Guo, Ying; Wagner, John A; Butterton, Joan R

    2015-01-01

    Doravirine is a novel non-nucleoside inhibitor of HIV-1 reverse transcriptase with potent activity against wild-type virus (95% inhibitory concentration 19 nM, 50% human serum). Doravirine has low potential to cause drug-drug interactions since it is primarily eliminated by oxidative metabolism and does not inhibit or significantly induce drug-metabolizing enzymes. The pharmacokinetics and safety of doravirine were investigated in two double-blind, dose-escalation studies in healthy males. Thirty-two subjects received single doses of doravirine (6-1,200 mg) or matching placebo tablets; 40 subjects received doravirine (30-750 mg) or matching placebo tablets once daily for 10 days. In addition, the effect of doravirine (120 mg for 14 days) on single-dose pharmacokinetics of the CYP3A substrate midazolam was evaluated (10 subjects). The maximum plasma concentration (Cmax) of doravirine was achieved within 1-5 h with an apparent terminal half-life of 12-21 h. Consistent with single-dose pharmacokinetics, steady state was achieved after approximately 7 days of once daily administration, with accumulation ratios (day 10/day 1) of 1.1-1.5 in the area under the plasma concentration-time curve during the dosing interval (AUC0-24 h), Cmax and trough plasma concentration (C24 h). All dose levels produced C24 h>19 nM. Administration of 50 mg doravirine with a high-fat meal was associated with slight elevations in AUC time zero to infinity (AUC0-∞) and C24 h with no change in Cmax. Midazolam AUC0-∞ was slightly reduced by coadministration of doravirine (geometric mean ratio 0.82, 90% CI 0.70, 0.97). There was no apparent relationship between adverse event frequency or intensity and doravirine dose. No rash or significant central nervous system events other than headache were reported. Doravirine is generally well tolerated in single doses up to 1,200 mg and multiple doses up to 750 mg once daily for up to 10 days, with a pharmacokinetic profile supportive of once-daily

  14. Randomised clinical trial

    Coyle, C; Crawford, G; Wilkinson, J

    2017-01-01

    BACKGROUND: Symptomatic breakthrough in proton pump inhibitor (PPI)-treated gastro-oesophageal reflux disease (GERD) patients is a common problem with a range of underlying causes. The nonsystemic, raft-forming action of alginates may help resolve symptoms. AIM: To assess alginate-antacid (Gaviscon...... Double Action, RB, Slough, UK) as add-on therapy to once-daily PPI for suppression of breakthrough reflux symptoms. METHODS: In two randomised, double-blind studies (exploratory, n=52; confirmatory, n=262), patients taking standard-dose PPI who had breakthrough symptoms, assessed by Heartburn Reflux...

  15. Angiotensin receptor blockade in acute stroke. The Scandinavian Candesartan Acute Stroke Trial: rationale, methods and design of a multicentre, randomised- and placebo-controlled clinical trial (NCT00120003)

    Sandset, Else Charlotte; Murray, Gordon; Boysen, Gudrun Margrethe

    2010-01-01

    AND DESIGN: The Scandinavian Candesartan Acute Stroke Trial is an international randomised, placebo-controlled, double-blind trial of candesartan in acute stroke. We plan to recruit 2500 patients presenting within 30 h of stroke (ischaemic or haemorrhagic) and with systolic blood pressure =140 mm......Hg. The recruited patients are randomly assigned to candesartan or placebo for 7-days (doses increasing from 4 to 16 mg once daily). Randomisation is performed centrally via a secure web interface. The follow-up period is 6-months. Patients are included from the following nine North-European countries: Norway...

  16. Purine derivatives excretion function in relation to the fiber/protein ratio in the diet of alpacas (Vicugna pacos)

    Rúa M., Viviana; Olazábal L., Juan; San Martín H., Felipe

    2017-01-01

    The aim of this study was to evaluate the relationship of the neutral detergent fibre/ crude protein on urinary excretion of purine derivatives (PD) in alpacas. The experimental design was a 3x3 Latin Square. Three male Huacaya alpacas, 2.5 years old, confined in individual pens were used. Feed was provided once daily and water ad libitum. Three treatments based on oat hay were used where the ratios of fibre/protein was obtained according to the proportions of stems and leaves. The treatments...

  17. Atenolol Is Associated with Lower Day of Surgery Heart Rate as compared to Long and Short-acting Metoprolol

    Schonberger, Robert B.; Brandt, Cynthia; Feinleib, Jessica; Dai, Feng; Burg, Matthew M.

    2012-01-01

    Objectives We analyzed the association between outpatient beta-blocker type and day-of-surgery heart rate in ambulatory surgical patients. We further investigated whether differences in day of surgery heart rate between atenolol and metoprolol could be explained by once-daily versus twice-daily dosing regimens. Design Retrospective observational study. Setting VA Hospital Participants Ambulatory surgical patients on chronic atenolol or metoprolol. Interventions None. Measurements and Main Results Using a propensity-score matched cohort, we compared day of surgery heart rates of patients prescribed atenolol versus metoprolol. We then differentiated between once-daily and twice-daily metoprolol formulations and compared day of surgery heart rates within a general linear model. Day of surgery heart rates in patients prescribed atenolol vs. any metoprolol formulation were slower by a mean of 5.1 beats/min (66.6 vs. 71.7; 95% CI of difference 1.9 to 8.3, p=0.002), a difference that was not observed in preoperative primary care visits. The general linear model demonstrated that patients prescribed atenolol (typically QD dosing) had a mean day of surgery heart rate 5.6 beats/min lower compared to patients prescribed once-daily metoprolol succinate (68.9 vs. 74.5; 95% CI of difference: −8.6 to −2.6, p<0.001) and 3.8 beats/minute lower compared to patients prescribed twice-daily metoprolol tartrate (68.9 vs. 72.7; 95% CI of difference: −6.1 to −1.6, p<0.001). Day of surgery heart rates were similar between different formulations of metoprolol (95% CI of difference: −1.0 to +4.6, p=0.22). Conclusions Atenolol is associated with lower day of surgery heart rate vs. metoprolol. The heart rate difference is specific to the day of surgery and is not explained by once-daily versus twice-daily dosing regimens. PMID:22889605

  18. Recent advances in prophylaxis against deep vein thrombosis.

    Wheatley, T; Veitch, P S

    1997-02-01

    The major development in DVT prophylaxis in recent years has been the introduction of low molecular weight heparins. Their main improvement compared with unfractionated heparin is in the convenience of a once daily dosage, but they have not yet convincingly been shown to be more effective or safer. A-V impulse boots may have an impact on knee and hip surgery but still face problems with patient acceptability. Probably the best way to ensure that more DVT are prevented is by clinicians maintaining a high level of awareness of the risk, and developing, and adhering to, local guidelines.

  19. Safety, Tolerability and Pharmacokinetics of the Serotonin 5-HT6 Receptor Antagonist, SUVN-502, in Healthy Young Adults and Elderly Subjects.

    Nirogi, Ramakrishna; Mudigonda, Koteshwara; Bhyrapuneni, Gopinadh; Muddana, Nageswara Rao; Goyal, Vinod Kumar; Pandey, Santosh Kumar; Palacharla, Raghava Choudary

    2018-05-01

    SUVN-502, a selective 5-HT6 receptor antagonist, was found to be active in preclinical models of cognitive deterioration suggesting a potential role in the treatment of dementia related to Alzheimer's disease. The objective of this study was to characterize the safety, tolerability and pharmacokinetics of SUVN-502 in healthy young adults and elderly subjects following single and multiple oral doses. Single doses (5, 15, 50, 100 and 200 mg SUVN-502) and multiple doses (50, 100 and 130 mg SUVN-502 once daily for 7 days) were evaluated in healthy young adults and multiple doses (50 and 100 mg SUVN-502 once daily for 14 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food, gender and age on SUVN-502 pharmacokinetics (100 mg single dose) was evaluated using an open-label, two-period, randomized, fed and fasted in a crossover design. SUVN-502 and M1 (major metabolite of SUVN-502) were monitored using validated analytical methods. SUVN-502 is safe and well tolerated up to the highest tested single dose of 200 mg in healthy young adults and multiple doses up to 130 mg for 7 days and 100 mg for 14 days in healthy young adults and elderly subjects, respectively. Exposures of SUVN-502 and M1 were more than dose-proportional over the evaluated dose range. Food and gender did not have a clinically meaningful effect on SUVN-502 exposure. The mean SUVN-502 total (AUC 0-∞ , and AUC 0-last ) and peak exposures (C max ) were 2.9- and 2.2-fold higher, respectively, in elderly subjects compared to young subjects. Steady-state was achieved for SUVN-502 and M1 within 7 days after once-daily dosing of SUVN-502. SUVN-502 exhibited an acceptable safety, tolerability and pharmacokinetic profile in healthy young adults and elderly subjects. Based on the above results, 50 and 100 mg once-daily doses of SUVN-502 were advanced to Phase 2 evaluation in patients with moderate AD.

  20. Darapladib, a lipoprotein-associated phospholipase A2 inhibitor, in diabetic macular edema

    Staurenghi, Giovanni; Ye, Li; Magee, Mindy H

    2015-01-01

    PURPOSE: To investigate the potential of lipoprotein-associated phospholipase A2 inhibition as a novel mechanism to reduce edema and improve vision in center-involved diabetic macular edema (DME). DESIGN: Prospective, multicenter, randomized, double-masked, placebo-controlled phase IIa study...... (AEs) and nonocular AEs were similar between treatment groups. CONCLUSIONS: Once-daily oral darapladib administered for 3 months demonstrated modest improvements in vision and macular edema that warrant additional investigation of this novel lipoprotein-associated phospholipase A2 inhibitory mechanism...

  1. A comparison of spirapril and isradipine in patients with diabetic nephropathy and hypertension

    Nørgaard, K; Jensen, T; Christensen, P

    1993-01-01

    The effects of spirapril and isradipine on blood pressure, urinary albumin excretion and sodium-volume homeostasis in hypertensive insulin-dependent diabetic patients with nephropathy were assessed. Fifteen Type 1 diabetic patients aged 28-53 years with a diabetes duration of 19-37 years were...... spirapril 6 mg once daily for 6 months in a double-blind design. Isradipine lowered ambulatory systolic blood pressure from 152 +/- 12 to 141 +/- 11 mmHg (p ... +/- 13 vs 143 +/- 11 mmHg (p

  2. Acute caries following radiation therapy in the nose/throat region. Prophylactic measures

    Roella, G; Johansen, E [Oslo Univ. (Norway); Pedersen, K N [Rochester Univ., NY (USA)

    1978-05-10

    Recent research indicates that xerostomia caused by irradiation of the salivary glands causes rampant caries by inducing a soft sucrose rich diet in this group of patients and by reduction of the buffer capacity and volume of the secretion. Whereas total extraction of the teeth before the irradiation started was previously the normal procedure in these patients, the teeth now can be maintained by very simple and inexpensive prophylactic measures, involving use of a gel containing 1% of soldium fluoride for 5 minutes once daily.

  3. Acute caries following radiation therapy in the nose/throat region

    Roella, G.; Johansen, E.; Pedersen, K.N.

    1978-01-01

    Recent research indicates that xerostomia caused by irradiation of the salivary glands causes rampant caries by inducing a soft sucrose rich diet in this group of patients and by reduction of the buffer capacity and volume of the secretion. Whereas total extraction of the teeth before the irradiation started was previously the normal procedure in these patients, the teeth now can be maintained by very simple and inexpensive prophylactic measures, involving use of a gel containing 1% of soldium fluoride for 5 minutes once daily. (Auth.)

  4. The INCA trial (Impact of NOD2 genotype-guided antibiotic prevention on survival in patients with liver Cirrhosis and Ascites): study protocol for a randomized controlled trial.

    Casper, Markus; Mengel, Martin; Fuhrmann, Christine; Herrmann, Eva; Appenrodt, Beate; Schiedermaier, Peter; Reichert, Matthias; Bruns, Tony; Engelmann, Cornelius; Grünhage, Frank; Lammert, Frank

    2015-03-08

    Patients with liver cirrhosis have a highly elevated risk of developing bacterial infections that significantly decrease survival rates. One of the most relevant infections is spontaneous bacterial peritonitis (SBP). Recently, NOD2 germline variants were found to be potential predictors of the development of infectious complications and mortality in patients with cirrhosis. The aim of the INCA (Impact of NOD2 genotype-guided antibiotic prevention on survival in patients with liver Cirrhosis and Ascites) trial is to investigate whether survival of this genetically defined high-risk group of patients with cirrhosis defined by the presence of NOD2 variants is improved by primary antibiotic prophylaxis of SBP. The INCA trial is a double-blind, placebo-controlled clinical trial with two parallel treatment arms (arm 1: norfloxacin 400 mg once daily; arm 2: placebo once daily; 12-month treatment and observational period). Balanced randomization of 186 eligible patients with stratification for the protein content of the ascites (INCA trial is first in the field of hepatology aimed at rapidly transferring and validating information on individual genetic risk into clinical decision algorithms. German Clinical Trials Register DRKS00005616 . Registered 22 January 2014. EU Clinical Trials Register EudraCT 2013-001626-26 . Registered 26 January 2015.

  5. OTC polyethylene glycol 3350 and pharmacists' role in managing constipation.

    Horn, John R; Mantione, Maria Marzella; Johanson, John F

    2012-01-01

    To define constipation, assess the pharmacist's role in identifying and treating constipation, and review clinical evidence for the efficacy, safety, and tolerability of polyethylene glycol (PEG) 3350 (MiraLAX-Merck Consumer Care), an osmotic laxative now available over the counter (OTC), across a variety of patient populations routinely encountered in pharmacy settings. Systematic PubMed search of the primary literature for constipation treatment guidelines and clinical trial results for PEG 3350. Pharmacists have a unique role in assisting patients with identifying and managing constipation. Multiple controlled clinical trials have established the efficacy, safety, and tolerability of PEG 3350 at its recommended dose of 17 g once daily. On the basis of this evidence, various professional groups have recommended PEG 3350 for use in improving stool frequency and consistency in patients with constipation. PEG 3350 is approved for short-term use, including treatment of constipation caused by medications. Pharmacists can play an important role in managing constipation with OTC agents. Compared with other available OTC agents, PEG 3350 can be recommended to patients suffering from constipation on the basis of a large body of clinical evidence supporting its efficacy and safety, as well as the high patient acceptance shown for its palatability and once-daily dosing.

  6. A novel dual GLP-1 and GIP incretin receptor agonist is neuroprotective in a mouse model of Parkinson's disease by reducing chronic inflammation in the brain.

    Cao, Lijun; Li, Dongfang; Feng, Peng; Li, Lin; Xue, Guo-Fang; Li, Guanglai; Hölscher, Christian

    2016-04-13

    The incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are growth factors. GLP-1 mimetics are on the market as treatments for type 2 diabetes. Both GLP-1 and GIP mimetics have shown neuroprotective properties in previous studies. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. Novel GLP-1/GIP dual-agonist peptides have been developed to treat diabetes. Here, we report the neuroprotective effects of a novel dual agonist (DA-JC1) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected once daily (20 mg/kg intraperitoneally) for 7 days and the dual agonist was coinjected once daily (50 nmol/kg intraperitoneally). We found that the drug reduced most of the MPTP-induced motor impairments in the rotarod, open-field locomotion, and muscle strength test. The number of tyrosine hydroxylase-positive neurons in the substantia nigra and striatum was reduced by MPTP and increased by DA-JC1. Synapse numbers (synaptophysin expression) were reduced in the substantia nigra and the striatum by MPTP and DA-JC1 reversed this effect. The activation of a chronic inflammation response by MPTP was considerably reduced by the dual agonist (DA) (astroglia and microglia activation). Therefore, dual agonists show promise as a novel treatment of PD.

  7. Thyroid aplasia in male sibling of heterozygotic twins born to the hyperthyroid mother treated with propylthiouracil during pregnancy (case report).

    Almarzouki, A A

    2012-01-01

    A 30-year-old pregnant female was diagnosed to have thyrotoxicosis (TSH= 0.005 µU/ml) at 13th week of gestation. Propylthiouracil (PTU; 200 mg daily) was prescribed to her and four weekly follow ups by the endocrinologist and obstetrician were ensured. At each examination TSH, FT4 and FT3 levels were normal and she became symptom free. Repeated ultrasound examination throughout the pregnancy did not reveal any fetal abnormality. The lady normally delivered heterozygotic twins. Umbilical cord blood of the baby boy twin showed a high TSH (541 µU/ml; reference range 0.270 - 4.20 μU/ml). He was started on thyroxine therapy (50 µg once daily). Ultrasound reported the absence of the thyroid gland. One month later TSH was within normal range and thyroxine dose was adjusted to 25 µg once daily. Repeated ultrasound confirmed the absence of thyroid gland. TSH was repeatedly normal. The boy is currently doing well on thyroxine replacement therapy. The other non-identical twin was a healthy girl with normal thyroid function tests and always thereafter. This case report suggested that PTU could be a hazardous drug to the fetus, since the mother gave birth to a baby with thyroid aplasia. PTU, Thyroid aplasia, Thyrotoxicosis, TSH.

  8. Silodosin: treatment of the signs and symptoms of benign prostatic hyperplasia.

    Curran, Monique P

    2011-05-07

    Silodosin is an α-adrenoceptor antagonist with high selectivity for α(1A)- relative to α(1B)- adrenoceptors. In men aged >50 years with benign prostatic hyperplasia (BPH), silodosin 8 mg once daily, compared with placebo, was associated with a significantly more rapid and effective improvement in the total International Prostate Symptom Score (IPSS) and the storage and voiding IPSS subscores in three 12-week, phase III trials conducted in Europe and the US. In the European trial, silodosin was at least as effective as tamsulosin 0.4 mg once daily in improving the total IPSS. Silodosin was significantly more effective than placebo (all three phase III trials) and tamsulosin (European phase III trial) in simultaneously improving nocturia, frequency and incomplete emptying, according to a post hoc analysis. Long-term, open-label extension trials demonstrated that silodosin provided sustained relief of the signs and symptoms of BPH for up to 1 year. Silodosin was generally well tolerated, and was associated with minimal cardiovascular adverse effects. Abnormal ejaculation, a class effect of α(1A)-adrenoceptor antagonists, was the most common silodosin-associated adverse reaction, but resulted in treatment withdrawal of only a limited number of patients. © 2011 Adis Data Information BV. All rights reserved.

  9. The efficacy and safety of lixivaptan in outpatients with heart failure and volume overload: results of a multicentre, randomized, double-blind, placebo-controlled, parallel-group study.

    Ghali, Jalal K; Orlandi, Cesare; Abraham, William T

    2012-06-01

    Volume overload is the dominant feature of decompensated heart failure (HF) and it often results in adverse clinical outcomes. Vasopressin receptor antagonists such as lixivaptan may provide effective volume unloading. This study assessed weight loss after 1 day and 8 weeks of treatment with lixivaptan in outpatients with HF and volume overload. This phase II, 8-week, multicentre, double-blind, parallel-group study randomized participants (2:1) to receive lixivaptan 100 mg or placebo once daily (in addition to standard HF therapy). Body weight and cardiovascular assessments were made at baseline, Day 1 (not cardiovascular), Weeks 1, 2, 4, and 8, and 7 days post-treatment. The Trail-making Test, part B (TMT-B) and the Medical Outcomes Survey 6-item cognitive function scale (MOS-6) were assessed at baseline and Week 4. The study randomized 170 participants (lixivaptan, n = 111; placebo, n = 59). Most (97.1%) were receiving pharmacological therapy for HF at baseline. Demographic characteristics were generally similar between the two groups. Body weight decreased significantly from baseline to Day 1 with lixivaptan vs. placebo (least-square mean change ± standard error: - 0.38 ± 0.08 kg vs. +0.13 ± 0.11 kg; P overload, lixivaptan 100 mg once daily, when added to standard therapy, reduced body weight, improved dyspnoea and orthopnoea, and was well tolerated. NCT01055912.

  10. Comparison of oral robenacoxib and carprofen for the treatment of osteoarthritis in dogs: a randomized clinical trial.

    Edamura, Kazuya; King, Jonathan N; Seewald, Wolfgang; Sakakibara, Nobuhiro; Okumura, Masahiro

    2012-09-01

    The efficacy and tolerability of robenacoxib for the treatment of osteoarthritis in dogs were evaluated in a prospective, multicenter, randomized, noninferiority design clinical trial. A total of 32 dogs presenting with osteoarthritis were allocated randomly to receive, orally once daily for 28 days, either 1-2 mg/kg robenacoxib (n=21) or 3.5-5 mg/kg carprofen (n=11). Dogs were assessed by clinicians and owners using numerical rating scale scores at baseline and days 14 and 28. The primary efficacy endpoint was the global functional disability score, which was the sum of clinician scores for standing posture, lameness at walk, lameness at trot, willingness to raise the contralateral limb and pain at palpation. There was a good to excellent level of efficacy in both treatment groups. Differences between days 14 and 28 compared to day 0 were significant for all 11 clinician and owner scores for robenacoxib, and for 6 of 11 scores for carprofen. The efficacy of robenacoxib was numerically superior to carprofen for all 13 endpoints, but differences were not statistically significant. For the global functional disability score, the estimated efficacy of robenacoxib was 1.244 (95% confidence interval 0.555-2.493) relative to carprofen. The tolerability of both treatments was good as assessed from adverse events, clinical signs, and hematology and serum biochemistry variables. In conclusion, once daily administration of robenacoxib tablets had noninferior efficacy and tolerability compared to carprofen for the treatment of the clinical signs of osteoarthritis in dogs.

  11. Role of rasagiline in treating Parkinson’s disease: effect on disease progression

    Irene A Malaty

    2009-05-01

    Full Text Available Irene A Malaty, Hubert H FernandezUniversity of Florida Movement Disorders Center, Gainesville, FL, USAAbstract: Rasagiline is a second generation, selective, irreversible monoamine oxidase type B (MAO-B inhibitor. It has demonstrated efficacy in monotherapy for early Parkinson’s disease (PD patients in one large randomized, placebo-controlled trial (TVP-1012 in Early Monotherapy for Parkinson’s Disease Outpatients, and has shown ability to reduce off time in more advanced PD patients with motor fluctuations in two large placebo-controlled trials (Parkinson’s Rasagiline: Efficacy and Safety in the Treatment of “Off”, and Lasting Effect in Adjunct Therapy With Rasagiline Given Once Daily. Preclinical data abound to suggest potential for neuroprotection by this compound against a variety of neurotoxic insults in cell cultures and in animals. The lack of amphetamine metabolites provides an advantage over the first generation MAO-B inhibitor selegiline. One large trial has investigated the potential for disease modification in PD patients (Attenuation of Disease progression with Azilect Given Once-daily and preliminary results maintain some possible advantage to earlier initiation of the 1 mg/day dose. The clinical significance of the difference detected remains a consideration.Keywords: rasagiline, Parkinson’s disease, neuroprotection, selegiline

  12. The role of rasagiline in the treatment of Parkinson’s disease

    Julie Leegwater-Kim

    2010-05-01

    Full Text Available Julie Leegwater-Kim1, Elena Bortan21Tufts University School of Medicine and Department of Neurology, Lahey Clinic, Burlington, MA, USA; 2Department of Neurology, Lahey Clinic, Burlington, MA, USAAbstract: Parkinson’s disease (PD is the second most common neurodegenerative disorder, affecting 1% to 2% of people older than 60 years. Treatment of PD consists of symptomatic therapies while neuroprotective strategies have remained elusive. Rasagiline is a novel, potent, and irreversible monoamine oxidase type B (MAO-B inhibitor which has been approved for treatment of PD. Rasagiline inhibits MAO-B more potently than selegiline and has the advantage of once-daily dosing. In several large, randomized, placebo-controlled trials, rasagiline has demonstrated efficacy as monotherapy in early PD and as adjunctive therapy in advanced PD. In addition, rasagiline has been shown to have neuroprotective effects in in vitro and in vivo studies. The recently completed delayed-start ADAGIO (Attenuation of Disease Progression with Azilect Given Once-daily trial suggests a potential disease-modifying effect for rasagiline 1 mg/day, though the clinical import of this finding has yet to be established.Keywords: rasagiline, monoamine oxidase inhibitor, Parkinson’s disease

  13. Role of rasagiline in treating Parkinson's disease: Effect on disease progression.

    Malaty, Irene A; Fernandez, Hubert H

    2009-08-01

    Rasagiline is a second generation, selective, irreversible monoamine oxidase type B (MAO-B) inhibitor. It has demonstrated efficacy in monotherapy for early Parkinson's disease (PD) patients in one large randomized, placebo-controlled trial (TVP-1012 in Early Monotherapy for Parkinson's Disease Outpatients), and has shown ability to reduce off time in more advanced PD patients with motor fluctuations in two large placebo-controlled trials (Parkinson's Rasagiline: Efficacy and Safety in the Treatment of "Off", and Lasting Effect in Adjunct Therapy With Rasagiline Given Once Daily). Preclinical data abound to suggest potential for neuroprotection by this compound against a variety of neurotoxic insults in cell cultures and in animals. The lack of amphetamine metabolites provides an advantage over the first generation MAO-B inhibitor selegiline. One large trial has investigated the potential for disease modification in PD patients (Attenuation of Disease progression with Azilect Given Once-daily) and preliminary results maintain some possible advantage to earlier initiation of the 1 mg/day dose. The clinical significance of the difference detected remains a consideration.

  14. Role of rasagiline in treating Parkinson’s disease: Effect on disease progression

    Malaty, Irene A; Fernandez, Hubert H

    2009-01-01

    Rasagiline is a second generation, selective, irreversible monoamine oxidase type B (MAO-B) inhibitor. It has demonstrated efficacy in monotherapy for early Parkinson’s disease (PD) patients in one large randomized, placebo-controlled trial (TVP-1012 in Early Monotherapy for Parkinson’s Disease Outpatients), and has shown ability to reduce off time in more advanced PD patients with motor fluctuations in two large placebo-controlled trials (Parkinson’s Rasagiline: Efficacy and Safety in the Treatment of “Off”, and Lasting Effect in Adjunct Therapy With Rasagiline Given Once Daily). Preclinical data abound to suggest potential for neuroprotection by this compound against a variety of neurotoxic insults in cell cultures and in animals. The lack of amphetamine metabolites provides an advantage over the first generation MAO-B inhibitor selegiline. One large trial has investigated the potential for disease modification in PD patients (Attenuation of Disease progression with Azilect Given Once-daily) and preliminary results maintain some possible advantage to earlier initiation of the 1 mg/day dose. The clinical significance of the difference detected remains a consideration. PMID:19753135

  15. Rasagiline: A second-generation monoamine oxidase type-B inhibitor for the treatment of Parkinson's disease.

    Chen, Jack J; Ly, Anh-Vuong

    2006-05-15

    The pharmacology, pharmacokinetics, clinical efficacy, and safety of rasagiline are reviewed. Rasagiline is a novel, investigational propargylamine that irreversibly and selectively inhibits monoamine oxidase type B (MAO-B). Rasagiline demonstrates complete and selective inhibition of MAO-B and is at least five times more potent than selegiline. Unlike selegiline, which is metabolized to amphetamine derivatives, rasagiline is biotransformed to the nonamphetamine compound aminoindan. Clinical studies have revealed that rasagiline is associated with improved outcomes in patients with early Parkinson's disease (PD) and also reduces "off" time in patients with moderate to advanced PD with motor fluctuations. Rasagiline is rapidly absorbed by the gastrointestinal tract and readily crosses the blood-brain barrier. The optimal therapeutic dosage is 0.5-1 mg administered orally once daily. Rasagiline appears to be well tolerated, although elderly patients may be more prone to treatment-emergent adverse cardiovascular and psychiatric effects. At the recommended therapeutic dosage of up to 1 mg once daily, tyramine restriction is unnecessary. In addition to MAO-B inhibition, rasagiline has demonstrated neuroprotective properties in experimental laboratory models. The mechanisms whereby rasagiline exerts neuroprotective effects are multifactorial and include upregulation of cellular antioxidant activity and antiapoptotic factors. Rasagiline is an investigational selective and irreversible inhibitor of MAO-B that has demonstrated efficacy and safety for the treatment of PD. Whether rasagiline is associated with clinically significant neuroprotection is the subject of ongoing clinical trials.

  16. Twelve-Week Treatment With Liraglutide as Add-on to Insulin in Normal-Weight Patients With Poorly Controlled Type 1 Diabetes

    Frandsen, Christian S; Dejgaard, Thomas F; Holst, Jens J

    2015-01-01

    OBJECTIVE: This study investigated the efficacy and safety of once-daily liraglutide 1.2 mg versus placebo as add-on to insulin treatment in normal-weight patients with poorly controlled type 1 diabetes. RESEARCH DESIGN AND METHODS: In a randomized (1:1), double-blind, placebo-controlled design, 40...... patients with type 1 diabetes (HbA1c ≥8% [64 mmol/mol]) received once-daily liraglutide 1.2 mg or placebo for 12 weeks. Continuous glucose monitoring was performed before and at the end of treatment. The primary end point was change in HbA1c. Secondary end points included change in insulin dose, weight...... was more frequently associated with gastrointestinal adverse effects. The incidence of hypoglycemia did not differ between groups. CONCLUSIONS: Liraglutide significantly reduces body weight and insulin requirements but has no additional effect on HbA1c in normal-weight patients with type 1 diabetes...

  17. Health-related quality of life assessments in osteoarthritis during NSAID treatment.

    de Bock, G H; Hermans, J; van Marwijk, H W; Kaptein, A A; Mulder, J D

    1996-08-01

    There is some evidence that nabumetone (1000 mg once daily) in comparison with piroxicam (20 mg once daily) in patients with OA in general practice is associated with a lower incidence and less severe occurrence of stomach pain but with more withdrawals due to lack of efficacy. The aim of this analysis was to investigate whether these differences are reflected in health-related quality of life assessments. Patients (n = 198) included in this study were selected in general practice according to a protocol. The patients were randomized and treated for a period of six weeks. Clinical assessments were performed by the general practitioner (CP) during treatment. The Sickness Impact Profile (SIP), the Activities of Daily Living (ADL), and a pain questionnaire were filled out by the patients before and after treatment. As measured with the SIP, the ADL and the pain questionnaire, there were no significant differences between nabumetone and piroxicam. The correlations between (changes in) patient assessments and (changes in) clinical assessments were low. The differences between the two drugs regarding withdrawals and adverse events were not reflected by patient health-related quality of life assessments. There was a low correlation between patient health-related quality of life assessment and clinical assessments. To get a complete picture of the efficacy and safety of a drug, patient health-related quality of life assessments should be a part of a clinical trial.

  18. Atovaquone and proguanil hydrochloride for prophylaxis of malaria.

    Shanks, G D; Kremsner, P G; Sukwa, T Y; van der Berg, J D; Shapiro, T A; Scott, T R; Chulay, J D

    1999-05-01

    The spread of drug-resistant malaria and appreciation of side effects associated with existing antimalarial drugs emphasize the need for new drugs to prevent malaria. The combination of atovaquone and proguanil hydrochloride was previously shown to be safe and highly effective for treatment of malaria, including multi-drug-resistant Plasmodium falciparum. We reviewed results of clinical trials that evaluated either a fixed-dose combination of atovaquone and proguanil hydrochloride for malaria prophylaxis or atovaquone alone for causal prophylactic activity against P. falciparum. In three placebo-controlled trials, 331 subjects received 250 mg atovaquone and 100 mg proguanil hydrochloride (or an equivalent dose based on body weight in children) once daily for 10 to 12 weeks. The overall efficacy for preventing parasitemia was 98%. Among 175 nonimmune volunteers taking the same dose of atovaquone/proguanil once daily for 10 weeks while temporarily residing in a malaria-endemic area, malaria developed in one patient who was noncompliant with therapy. Results of volunteer challenge studies indicate that both atovaquone and proguanil have causal prophylactic activity directed against the liver stages of P. falciparum. Adverse events occurred with similar or lower frequencies in subjects treated with atovaquone/proguanil compared to placebo. Less than 1% of patients discontinued from these studies due to a treatment-related adverse event. A fixed-dose combination of atovaquone and proguanil hydrocloride is a promising new alternative for malaria prophylaxis.

  19. Coagulation profile in patients undergoing video-assisted thoracoscopic lobectomy: A randomized, controlled trial.

    Thomas Decker Christensen

    Full Text Available Knowledge about the impact of Low-Molecular-Weight Heparin (LMWH on the coagulation system in patients undergoing minimal invasive lung cancer surgery is sparse. The aim of this study was to assess the effect of LMWH on the coagulation system in patients undergoing Video-Assisted Thoracoscopic Surgery (VATS lobectomy for primary lung cancer.Sixty-three patients diagnosed with primary lung cancer undergoing VATS lobectomy were randomized to either subcutaneous injection with dalteparin (Fragmin® 5000 IE once daily or no intervention. Coagulation was assessed pre-, peri-, and the first two days postoperatively by standard coagulation blood test, thromboelastometry (ROTEM® and thrombin generation.Patients undergoing potential curative surgery for lung cancer were not hypercoagulable preoperatively. There was no statistically significant difference in the majority of the assessed coagulation parameters after LMWH, except that the no intervention group had a higher peak thrombin and a shorter INTEM clotting time on the first postoperative day and a lower fibrinogen level on the second postoperative day. A lower level of fibrin d-dimer in the LMWH group was found on the 1. and 2.postoperative day, although not statistical significant. No differences were found between the two groups in the amount of bleeding or number of thromboembolic events.Use of LMWH administered once daily as thromboprophylaxis did not alter the coagulation profile per se. As the present study primarily evaluated biochemical endpoints, further studies using clinical endpoints are needed in regards of an optimized thromboprophylaxis approach.

  20. Preclinical Evaluations To Identify Optimal Linezolid Regimens for Tuberculosis Therapy

    Drusano, George L.; Adams, Jonathan R.; Rodriquez, Jaime L.; Jambunathan, Kalyani; Baluya, Dodge L.; Brown, David L.; Kwara, Awewura; Mirsalis, Jon C.; Hafner, Richard; Louie, Arnold

    2015-01-01

    ABSTRACT Linezolid is an oxazolidinone with potent activity against Mycobacterium tuberculosis. Linezolid toxicity in patients correlates with the dose and duration of therapy. These toxicities are attributable to the inhibition of mitochondrial protein synthesis. Clinically relevant linezolid regimens were simulated in the in vitro hollow-fiber infection model (HFIM) system to identify the linezolid therapies that minimize toxicity, maximize antibacterial activity, and prevent drug resistance. Linezolid inhibited mitochondrial proteins in an exposure-dependent manner, with toxicity being driven by trough concentrations. Once-daily linezolid killed M. tuberculosis in an exposure-dependent manner. Further, 300 mg linezolid given every 12 hours generated more bacterial kill but more toxicity than 600 mg linezolid given once daily. None of the regimens prevented linezolid resistance. These findings show that with linezolid monotherapy, a clear tradeoff exists between antibacterial activity and toxicity. By identifying the pharmacokinetic parameters linked with toxicity and antibacterial activity, these data can provide guidance for clinical trials evaluating linezolid in multidrug antituberculosis regimens. PMID:26530386

  1. Efficacy of topotecan treatment on antioxidant enzymes and TBA-RS levels in submandibular glands of rabbits: an experimental study.

    Muluk, Nuray Bayar; Kisa, Uçler; Kaçmaz, Murat; Apan, Alpaslan; Koç, Can

    2005-01-01

    The aim of this study was to investigate the effects of topotecan (Hycamtin), a topoisomerase I inhibiting anticancer agent, on antioxidant enzymes (SOD, CAT, and GSH-Px) and TBA-RS values of the submandibular glands of the rabbits. The study was conveyed in two groups (Group I, II) and control with a total of 24 rabbits. Eight rabbits in group I received intravenous (i.v.) topotecan (0.25 mg/kg once daily) for 3 days. Eight rabbits in group II received i.v. topotecan (0.5 mg/kg once daily) for 3 days. On the 15th day after administration of topotecan, submandibular glands were removed and levels of the SOD, CAT, and GSH-Px and the TBA-RS in the submandibular glands of the rabbits were examined. SOD, CAT, and GSH-Px values were significantly higher in high-dose topotecan group compared to control group (P TBA-RS values were significantly higher in high-dose topotecan group compared to low-dose topotecan group (P TBA-RS values in group II showed that permanent damage was present because of high-dose topotecan administration in the submandibular glands of the rabbits.

  2. The antihypertensive effect of amlodipine in cats

    D. Morar,

    2011-06-01

    Full Text Available The purpose of the study was to evaluate the effect of amlodipine on blood pressure and renal function in cats with arterial hypertension secondary to chronic renal failure. The research was conducted on 11 cats, aged between 7 and 14.5 years, diagnosed with arterial hypertension secondary to chronic renal failure. Systolic blood pressure (SBP, diastolic blood pressure (DBP, mean arterial pressure (MBP and pulse rate were determined by oscillometric method, before and after 7, 30 or 120 days of treatment with amlodipine. At the beginning of treatment, all cats were receiving 0.625 mg amlodipine once daily and after 7 days oftreatment, in five cats, the dose was increased to 1.25 mg amlodipine, once daily. Before amlodipine administration the mean values of SBP/DBP were 175 ± 13.2 mmHg/119 ± 7.2 mmHg and after 30 days of treatment, the mean values of the SBP/DBP were reduced by 27.9/25.4 mmHg (p<0,001. After 120 days of treatment with amlodipine mean values of SBP/DBP were lower with 32/31 mmHg compared with baseline values (p<0.001. The treatment with amlodipine did not significantly affect the values of blood biochemical parameters of renal profile.

  3. Effect of casopitant, a novel NK-1 antagonist, on the pharmacokinetics of dolasetron and granisetron.

    Adams, Laurel M; Johnson, Brendan; Zhang, Ke; Yue, Lin; Kirby, Lyndon C; Lebowitz, Peter; Stoltz, Randall

    2009-09-01

    The objective of this study was to characterize the impact of casopitant, a novel neurokinin-1 receptor antagonist under investigation for the prevention of postoperative and chemotherapy-induced nausea and vomiting, on the pharmacokinetics of the commonly prescribed 5-hydroxytryptamine receptor 3 receptor antagonists, dolasetron or granisetron. In a phase I, open-label, two-part, two-period, single-sequence study, two cohorts of healthy subjects received either oral dolasetron (100 mg once daily for 3 days) or oral granisetron (2 mg once daily for 3 days) alone (period 1) and combined with oral casopitant, 150 mg day 1, 50 mg days 2 and 3 (period 2). Pharmacokinetics of hydrodolasetron and granisetron were assessed on days 1 and 3 of each period. Log-transformed area under the curve (AUC) and Cmax were statistically analyzed by performing an analysis of variance. Eighteen subjects were enrolled in the dolasetron cohort; nine subjects were CYP2D6 extensive metabolizers (EMs) and nine subjects were CYP2D6 poor metabolizers. Nineteen subjects were enrolled in the granisetron cohort. The largest changes in hydrodolasetron exposure after coadministration with casopitant were seen in CYP2D6 EMs, with a 24% increase in hydrodolasetron AUC on day 1 and 30% increase in Cmax on days 1 and 3. All other changes in hydrodolasetron exposure were granisetron exposure was not altered to any relevant extent (granisetron was well tolerated.

  4. Could edaravone prevent gentamicin ototoxicity? An experimental study.

    Turan, M; Ciğer, E; Arslanoğlu, S; Börekci, H; Önal, K

    2017-02-01

    Clinical application of gentamicin may cause nephrotoxicity and ototoxicity. Our study is the first study to investigate the protective effects of edaravone against the gentamicin-induced ototoxicity. We investigated the protective effect of intraperitoneal (i.p.) edaravone application against gentamicin-induced ototoxicity in guinea pigs. Fourteen guinea pigs were divided into two equal groups consisting of a control group and a study group. One-hundred sixty milligrams per kilogram subcutaneous gentamicin and 0.3 mL i.p. saline were applied simultaneously once daily to seven guinea pigs in the control group (group 1). One-hundred sixty milligrams per kilogram gentamicin was applied subcutaneously and 3 mg/kg edaravone was applied intraperitoneally once daily for 7 days simultaneously to seven guinea pigs in the study group (group 2). Following the drug application, auditory brainstem response measurements were performed for the left ear on the 3rd and 7th days. Hearing threshold values of the group 1 and group 2 measured in the 3rd day of the study were detected as 57.14 ± 4.88 and 82.86 ± 7.56, respectively. This difference was statistically significant ( p edaravone-administered group 2 and that of group 1 without edaravone was found. These differences show that systemic edaravone administration could diminish ototoxic effects of gentamicin and the severity of the hearing loss.

  5. Update on the management of ulcerative colitis: treatment and maintenance approaches focused on MMX® mesalamine. [Corrigendum

    Nanda K

    2013-01-01

    Full Text Available Nanda K, Moss AC.Clinical Pharmacology: Advances and Applications. 2012, 4:41–50.The authors apologize for errors on Tables 1, 2, and 3.Table1Citation 40, Hussain et al, should have been citation 44, Shire US Inc.Table 2Lichtenstein et al data, the confidence interval (CI of the odds ratio for achieving remission with MMX mesalamine 1.2 g twice daily (1.44–8.41 should be listed as a 97.5% CI rather than a 95% CI.Table 3Prantera et al, the MMX mesalamine 2.4 g once daily cohort should have an N value of 156, not 162, and the 12-month relapse rate should be 25.0%, not 15.0%.Pramtera et al, the Asacol 2.4 g once daily cohort should be labeled "Asacol 2.4 g/day twice daily", and should have an N value of 167, not 156.Kane et al, the N value should be 194, not 167.Read the original article

  6. A multinational randomized, controlled, clinical trial of etoricoxib in the treatment of rheumatoid arthritis [ISRCTN25142273

    Zhao Peng

    2002-05-01

    Full Text Available Abstract Background Etoricoxib is a highly selective COX-2 inhibitor which was evaluated for the treatment of rheumatoid arthritis (RA. Methods Double-blind, randomized, placebo and active comparator-controlled, 12-week study conducted at 67 sites in 28 countries. Eligible patients were chronic NSAID users who demonstrated a clinical worsening of arthritis upon withdrawal of prestudy NSAIDs. Patients received either placebo, etoricoxib 90 mg once daily, or naproxen 500 mg twice daily (2:2:1 allocation ratio. Primary efficacy measures included direct assessment of arthritis by counts of tender and swollen joints, and patient and investigator global assessments of disease activity. Key secondary measures included the Stanford Health Assessment Questionnaire, patient global assessment of pain, and the percentage of patients who achieved ACR20 responder criteria response (a composite of pain, inflammation, function, and global assessments. Tolerability was assessed by adverse events and routine laboratory evaluations. Results 1171 patients were screened, 891 patients were randomized (N = 357 for placebo, N = 353 for etoricoxib, and N = 181 for naproxen, and 687 completed 12 weeks of treatment (N = 242 for placebo, N = 294 for etoricoxib, and N = 151 for naproxen. Compared with patients receiving placebo, patients receiving etoricoxib and naproxen showed significant improvements in all efficacy endpoints (p Conclusions In this study, etoricoxib 90 mg once daily was more effective than placebo and similar in efficacy to naproxen 500 mg twice daily for treating patients with RA over 12 weeks. Etoricoxib 90 mg was generally well tolerated in RA patients.

  7. Efficacy and safety of oral tinidazole and metronidazole in treatment of bacterial vaginosis: a randomized control trial

    Zahra Abbaspoor

    2014-05-01

    Full Text Available Aims: Oral metronidazole 500 mg twice a day for one week is currently the treatment of choice for bacterial vaginosis (BV. Complete treatment by this regimen takes time and occurs less often. This drug has significant side effects too. Using a drug in the shortest treatment course may increases the success of treatment. To evaluate the effectiveness and safety of oral tinidazole compare to metronidazole in treatment of BV.Methods: In this randomized, controlled, double-blind, comparative, clinical trial, 110 non-pregnant women aged between 15-45 years with confirmed diagnosis of BV by Amsels criteria were randomly assigned to receive either 2 g tinidazole tablet once daily for 2 days (n=55 or 500 mg metronidazole table twice daily for 7 days (n=55.The cure and recurrence rate were evaluated in both groups after 2 and 4 weeks follow up visits. For statistical analysis t-test,   test, fisher's exact test and Mann-Whitney test were used.Results: The results showed that cure rate after 2 weeks in tinidazole tablet group was 84.6٪ and in metronidazole group was 85.4٪ (p=0.9, and after 4 weeks recurrence rate in tinidazole and metronidazole groups was 6.9٪and 12.1٪respectively (P=0.3.Conclusions: Tinidazole table 2 g once daily for 2 days is as effective as metronidazole tablet 500 mg twice a day for 7 days in treatment of BV.

  8. Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: a randomized, double-blind, placebo-controlled trial

    Tomaschitz Andreas

    2012-09-01

    Full Text Available Abstract Background Increasing evidence suggests the bidirectional interplay between parathyroid hormone and aldosterone as an important mechanism behind the increased risk of cardiovascular damage and bone disease observed in primary hyperparathyroidism. Our primary object is to assess the efficacy of the mineralocorticoid receptor-blocker eplerenone to reduce parathyroid hormone secretion in patients with parathyroid hormone excess. Methods/design Overall, 110 adult male and female patients with primary hyperparathyroidism will be randomly assigned to eplerenone (25 mg once daily for 4 weeks and 4 weeks with 50 mg once daily after dose titration] or placebo, over eight weeks. Each participant will undergo detailed clinical assessment, including anthropometric evaluation, 24-h ambulatory arterial blood pressure monitoring, echocardiography, kidney function and detailed laboratory determination of biomarkers of bone metabolism and cardiovascular disease. The study comprises the following exploratory endpoints: mean change from baseline to week eight in (1 parathyroid hormone(1–84 as the primary endpoint and (2 24-h systolic and diastolic ambulatory blood pressure levels, NT-pro-BNP, biomarkers of bone metabolism, 24-h urinary protein/albumin excretion and echocardiographic parameters reflecting systolic and diastolic function as well as cardiac dimensions, as secondary endpoints. Discussion In view of the reciprocal interaction between aldosterone and parathyroid hormone and the potentially ensuing target organ damage, the EPATH trial is designed to determine whether eplerenone, compared to placebo, will effectively impact on parathyroid hormone secretion and improve cardiovascular, renal and bone health in patients with primary hyperparathyroidism. Trial registration ISRCTN33941607

  9. Targeting nocturnal hypertension in type 2 diabetes mellitus.

    Rossen, Niklas Blach; Knudsen, Søren Tang; Fleischer, Jesper; Hvas, Anne-Mette; Ebbehøj, Eva; Poulsen, Per Løgstrup; Hansen, Klavs Würgler

    2014-11-01

    Several studies in different populations have suggested that nighttime blood pressure (BP) is a stronger predictor of cardiovascular events than daytime BP. Consequently, treatment strategies to target nighttime BP have come into focus. The aim of the present study was to investigate the effect of change of administration time of antihypertensive drugs. We included 41 patients with type 2 diabetes mellitus and nocturnal hypertension (nighttime systolic BP >120 mm Hg) in an open-label, crossover study. Patients were randomized to 8 weeks of either morning or bedtime administration of all of the individual's once-daily antihypertensive drugs, followed by 8 weeks of switched dosing regimen. Bedtime administration of antihypertensive drugs resulted in a significant reduction in nighttime (7.5 mm Hg; Pdiabetes mellitus and nocturnal hypertension, administration of once-daily antihypertensive drugs at bedtime may be favorable. The increased nocturnal natriuresis may reflect increased effect of bedtime-administered thiazides and renin-angiotensin system inhibitors, suggesting a potential mechanism of the observed effects on BP with chronotherapeutic intervention. © 2014 American Heart Association, Inc.

  10. Lixisenatide as add-on therapy to basal insulin

    Brown DX

    2013-12-01

    Full Text Available Dominique Xavier Brown, Emma Louise Butler, Marc Evans Diabetes Department, University Hospital Llandough, Cardiff, UK Abstract: Many patients with type 2 diabetes mellitus do not achieve target glycosylated hemoglobin A1c levels despite optimally titrated basal insulin and satisfactory fasting plasma glucose levels. Current evidence suggests that HbA1c levels are dictated by both basal glucose and postprandial glucose levels. This has led to a consensus that postprandial glucose excursions contribute to poor glycemic control in these patients. Lixisenatide is a once-daily, prandial glucagon-like peptide 1 (GLP-1 receptor agonist with a four-fold affinity for the GLP-1 receptor compared with native GLP-1. Importantly, lixisenatide causes a significant delay in gastric emptying time, an important determinant of the once-daily dosing regimen. An exendin-4 mimetic with six lysine residues removed at the C-terminal, lixisenatide has pronounced postprandial glucose-lowering effects, making it a novel incretin agent for use in combination with optimally titrated basal insulin. Lixisenatide exerts profound effects on postprandial glucose through established mechanisms of glucose-dependent insulin secretion and glucagon suppression in combination with delayed gastric emptying. This review discusses the likely place that lixisenatide will occupy in clinical practice, given its profound effects on postprandial glucose and potential to reduce glycemic variability. Keywords: lixisenatide, add-on therapy, insulin, GLP-1 receptor agonist, postprandial glucose, pharmacodynamics

  11. Efficacy of SCH27899 in an Animal Model of Legionnaires' Disease Using Immunocompromised A/J Mice

    Brieland, Joan K.; Loebenberg, David; Menzel, Fred; Hare, Roberta S.

    2000-01-01

    The efficacy of SCH27899, a new everninomicin antibiotic, against replicative Legionella pneumophila lung infections in an immunocompromised host was evaluated using a murine model of Legionnaires' disease. A/J mice were immunocompromised with cortisone acetate and inoculated intratracheally with L. pneumophila serogroup 1 (105 CFU per mouse). At 24 h postinoculation, mice were administered either SCH27899 (6 to 60 mg/kg [MPK] intravenously) or a placebo once daily for 5 days, and mortality and intrapulmonary growth of L. pneumophila were assessed. In the absence of SCH27899, there was 100% mortality in L. pneumophila-infected mice, with exponential intrapulmonary growth of the bacteria. In contrast, administration of SCH27899 at a dose of ≥30 MPK resulted in ≥90% survival of infected mice, which was associated with inhibition of intrapulmonary growth of L. pneumophila. In subsequent studies, the efficacy of SCH27899 was compared to ofloxacin (OFX) and azithromycin (AZI). Administration of SCH27899, OFX, or AZI at a dose of ≥30 MPK once daily for 5 days resulted in ≥85% survival of infected mice and inhibition of intrapulmonary growth of the bacteria. However, L. pneumophila CFU were recovered in lung homogenates following cessation of therapy with all three antibiotics. These studies demonstrate that SCH27899 effectively prevents fatal replicative L. pneumophila lung infection in immunocompromised A/J mice by inhibition of intrapulmonary growth of the bacteria. However, in this murine model of pulmonary legionellosis, SCH27899, like OFX and AZI, was bacteriostatic. PMID:10770771

  12. A randomized controlled trial comparing alpha blocker (tamsulosin) and anticholinergic (solifenacin) in treatment of ureteral stent-related symptoms.

    El-Nahas, Ahmed R; Tharwat, Mohamed; Elsaadany, Mohamed; Mosbah, Ahmed; Gaballah, Mohamed A

    2016-07-01

    To compare the effectiveness of tamsulosin and solifenacin in relieving ureteral stents related symptoms. A randomized controlled trial was conducted between January 2013 and July 2014. Inclusion criteria were patients aged 20-50 years who underwent temporary unilateral ureteral stent for drainage of calcular upper tract obstruction or after ureteroscopic lithotripsy. Patients with history of lower urinary tract symptoms before stent placement, stents that were fixed after open or laparoscopic procedures, and those who developed complications related to the primary procedure were not included. Eligible patients were randomly assigned to 1 of 3 groups using computer-generated random tables. Patients in group 1 received placebo, patients in group 2 received tamsulosin 0.4 mg once daily, and those in group 3 received solifenacin 5 mg once daily. Ureteral Stent Symptom Questionnaire (USSQ) was answered by all patients 1-2 weeks after stent placement. The primary outcome was the comparison of total score of USSQ between all groups. The study included 131 patients. All baseline characteristics (age, sex, side, indication, length, and duration of stent) were comparable for all groups. Total USSQ score was 61 in solifenacin group, 76 in tamsulosin group, and 83 in control group (P tamsulosin group (P tamsulosin alone or solifenacin alone in patients with ureteral stents can improve the quality of life by decreasing ureteral stent-related symptoms. Solifenacin was better than tamsulosin. CLINICALTRIAL. NCT01880619.

  13. Esomeprazole treatment of frequent heartburn: two randomized, double-blind, placebo-controlled trials.

    Peura, David A; Traxler, Barry; Kocun, Christopher; Lind, Tore

    2014-07-01

    To determine the efficacy of a 14-day regimen of esomeprazole 20 mg for the treatment of frequent heartburn in subjects who are likely to self-treat with over-the-counter medications without consulting a health care provider. Adults with frequent heartburn ≥ 2 days per week in the past 4 weeks were randomly assigned to 14-day double-blind treatment with esomeprazole 20 mg once daily or placebo in 2 identical multicenter studies (ClinicalTrials.gov identifiers: NCT01370525, NCT01370538). The primary efficacy outcome was percentage of heartburn-free 24-hour days across 14 days. Secondary efficacy outcomes included heartburn resolution, defined as heartburn ≤ 2 days over 14 days, and percentages of subjects reporting ≤ 1 day with heartburn in the first and final weeks of treatment. Subjects recorded data in daily self-assessment diaries. The percentage of heartburn-free 24-hour days over 14 days was significantly higher (P heartburn resolution over 14 days and in the first and final weeks compared with placebo. Within the first 4 days, the proportion of subjects with heartburn-free days was significantly greater with esomeprazole 20 mg versus placebo. Treatment was generally well tolerated, with a safety pattern consistent with the known profile for esomeprazole. A 14-day regimen of esomeprazole 20 mg once daily was effective for treating frequent heartburn in subjects who are likely to self-treat with over-the-counter medications.

  14. Role of anti-thrombotic therapy for recurrent pregnancy loss due to anti-phospholipid syndrome

    Fawad, S.

    2010-01-01

    Background: Recurrent pregnancy loss is a major health problem effecting 1 to 2% of women of reproductive age. Its causes range from chromosomal abnormalities to endocrinological factors and thrombophilia related factors. Treating thrombophilia s especially anti phospholipid syndrome with low dose aspirin and low molecular weight heparin improves foetal outcome. This study will add local data to already existing knowledge. Method: Sixty selected patients from gynaecology OPD of Aero Hospital with clinical and/or serological findings of anti phospholipid syndrome from February 2009 to January 2011 were given aspirin 75 mg once daily and enoxaparine 40 mg subcutaneously once daily from 6 - 8 weeks to 35 and 37 weeks respectively. Results : Ninety-three percent of patients achieved live birth. Out of these 75% patients delivered at term and 18% had preterm delivered. Four (7%) had early pregnancy loss and only one had early neonatal death due to extreme prematurity. None of patients experienced any major hemorrhagic complications . Conclusion: Use of low dose aspirin and low molecular weight heparin is safe in pregnancy and improve foetal outcome in patients with recurrent pregnancy loss due to anti phospholipids syndrome. (author)

  15. Mixed Cutaneous Infection Caused by Mycobacterium szulgai and Mycobacterium intermedium in a Healthy Adult Female: A Rare Case Report

    Amresh Kumar Singh

    2015-01-01

    Full Text Available Nontuberculous mycobacteria (NTMs are ubiquitous and are being increasingly reported as human opportunistic infection. Cutaneous infection caused by mixed NTM is extremely rare. We encountered the case of a 46-year-old female, who presented with multiple discharging sinuses over the lower anterior abdominal wall (over a previous appendectomy scar for the past 2 years. Microscopy and culture of the pus discharge were done to isolate and identify the etiological agent. Finally, GenoType Mycobacterium CM/AS assay proved it to be a mixed infection caused by Mycobacterium szulgai and M. intermedium. The patient was advised a combination of rifampicin 600 mg once daily, ethambutol 600 mg once daily, and clarithromycin 500 mg twice daily to be taken along with periodic follow-up based upon clinical response as well as microbiological response. We emphasize that infections by NTM must be considered in the etiology of nonhealing wounds or sinuses, especially at postsurgical sites.

  16. A pharmacoeconomic evaluation of two new products for the treatment of overactive bladder.

    Arikian, S R; Casciano, J; Doyle, J J; Tarride, J E; Casciano, R N

    2000-02-01

    The objective of this study is to evaluate the cost effectiveness of two new treatments for overactive bladder: once-daily controlled-release oxybutynin, and twice-daily tolterodine, with a comparison with oxybutynin immediate release. Also estimated are the potential cost savings to a health plan budget resulting from increased utilization of the most cost-effective treatment. The design is a decision-tree model based on clinical trial data and expert panel estimates with a six-month time horizon conducted from a payer perspective. The primary outcome measure used in the analysis was treatment success, with success defined as zero incontinence episodes per week. A secondary outcome measure was the expected number of continent days. As first-line therapy, controlled-release oxybutynin is the most cost-effective treatment as measured by expected cost per success and expected cost per continent days. Controlled-release, once-daily oxybutynin yielded the highest expected success rate and the highest number of expected continent days. The expected cost of treatment with controlled-release oxybutynin was lower than tolterodine and equivalent to immediate-release oxybutynin. Increased utilization of controlled-release oxybutynin results in an estimated saving of $0.007 to $0.026 per member per month for a hypothetical HMO. The model was robust, incorporating all assumptions based on univariate and multivariate sensitivity analysis. Initiating treatment with controlled-release oxybutynin is the most cost-effective approach to treatment for overactive bladder.

  17. Prevalence and Treatment Management of Oropharyngeal Candidiasis in Cancer Patients: Results of the French Candidoscope Study

    Gligorov, Joseph; Bastit, Laurent; Gervais, Honorine; Henni, Mehdi; Kahila, Widad; Lepille, Daniel; Luporsi, Elisabeth; Sasso, Giuseppe; Varette, Charles; Azria, David

    2011-01-01

    Purpose: The aim of this pharmaco-epidemiological study was to evaluate the prevalence of oropharyngeal candidiasis (OPC) in cancer patients treated with chemotherapy and/or radiotherapy. Methods and Materials: Signs and symptoms of OPC were noted for all patients. Antifungal therapeutic management was recorded in OPC patients. Patients receiving local antifungal treatments were monitored until the end of treatment. Results: Enrolled in the study were 2,042 patients with solid tumor and/or lymphoma treated with chemotherapy and/or another systemic cancer treatment and/or radiotherapy. The overall prevalence of OPC was 9.6% (95% confidence interval, 8.4%-11.0%] in this population. It was most frequent in patients treated with combined chemoradiotherapy (22.0%) or with more than two cytotoxic agents (16.9%). Local antifungal treatments were prescribed in 75.0% of OPC patients as recommended by guidelines. The compliance to treatment was higher in patients receiving once-daily miconazole mucoadhesive buccal tablet (MBT; 88.2%) than in those treated with several daily mouthwashes of amphotericin B (40%) or nystatin (18.8%). Conclusion: OPC prevalence in treated cancer patients was high. Local treatments were usually prescribed as per guidelines. Compliance to local treatments was better with once-daily drugs.

  18. Extract of Fructus Cannabis Ameliorates Learning and Memory Impairment Induced by D-Galactose in an Aging Rats Model

    Ning-Yuan Chen

    2017-01-01

    Full Text Available Hempseed (Cannabis sativa L. has been used as a health food and folk medicine in China for centuries. In the present study, we sought to define the underlying mechanism by which the extract of Fructus Cannabis (EFC protects against memory impairment induced by D-galactose in rats. To accelerate aging and induce memory impairment in rats, D-galactose (400 mg/kg was injected intraperitoneally once daily for 14 weeks. EFC (200 and 400 mg/kg was simultaneously administered intragastrically once daily in an attempt to slow the aging process. We found that EFC significantly increased the activity of superoxide dismutase, while lowering levels of malondialdehyde in the hippocampus. Moreover, EFC dramatically elevated the organ indices of some organs, including the heart, the liver, the thymus, and the spleen. In addition, EFC improved the behavioral performance of rats treated with D-galactose in the Morris water maze. Furthermore, EFC inhibited the activation of astrocytes and remarkably attenuated phosphorylated tau and suppressed the expression of presenilin 1 in the brain of D-galactose-treated rats. These findings suggested that EFC exhibits beneficial effects on the cognition of aging rats probably by enhancing antioxidant capacity and anti-neuroinflammation, improving immune function, and modulating tau phosphorylation and presenilin expression.

  19. Regional GABA concentration and [3H]-diazepam binding in rat brain following repeated electroconvulsive shock

    Bowdler, J.M.; Green, A.R.; Minchin, M.C.W.; Nutt, D.J.

    1983-01-01

    It has been confirmed that 24 hours following a series of electroconvulsive shocks (ECS) given once daily for 10 days (ECS x 10) to rats there is an increase in GABA concentration in the corpus striatum. A similar change was seen after the ECS had been given to rats anaesthetised with halothane, or when 5 ECS were given spread out over 10 days, the rats being anaesthetised during the ECS. A daily convulsion for 10 days elicited by flurothyl exposure resulted in an increased striatal GABA concentration, but also increased the GABA concentration in the hypothalamus, hippocampus and cortex. The increase in striatal GABA concentration was present 24 hours after ECS daily for 5 days or 3 days after ECS daily for 10 days. No change in [ 3 H]-diazepam binding was seen in hippocampus, cortex or corpus striatum 24 hours after the last of 10 once daily ECS. The increase in striatal GABA concentration was therefore seen at all times when enhanced monoaminemediated behaviours have been demonstrated following seizures. (Author)

  20. Clobetasol propionate shampoo 0.05% is efficacious and safe for long-term control of scalp psoriasis.

    Poulin, Yves; Papp, Kim; Bissonnette, Robert; Guenther, Lyn; Tan, Jerry; Lynde, Charles; Kerrouche, Nabil; Villemagne, Hervé

    2010-01-01

    Clobetasol propionate (CP) shampoo 0.05% is an efficacious and safe treatment for scalp psoriasis. The aim of this double-blind, randomized, placebo-controlled study was to determine if CP shampoo is suitable for long-term disease control. Participants with moderate to severe scalp psoriasis (global severity score [GSS] of 3 or 4 on a scale of 0 [clear] to 5 [very severe]) first received once daily CP shampoo treatment for up to 4 weeks. Responders were subsequently randomized to receive the CP shampoo or vehicle twice weekly maintenance regimen for up to 6 months. When relapse occurred (defined as GSS > 2), participants resumed once daily CP shampoo treatment; when symptoms diminished (GSS shampoo did not relapse compared with participants treated with vehicle (P shampoo group. After 6 months 31.1% (33/106) of participants in the CP shampoo group were still relapse free versus 8.1% (9/111) of participants in the vehicle group. There was no greater incidence of skin atrophy, telangiectasia, or hypothalamic-pituitary-adrenal (HPA) axis suppression in the CP shampoo group compared with the vehicle group. Clobetasol propionate shampoo is efficacious and safe for acute management and long-term maintenance of moderate to severe scalp psoriasis.

  1. The effect of itopride combined with lansoprazole in patients with laryngopharyngeal reflux disease.

    Chun, Byung-Joon; Lee, Dong-Soo

    2013-03-01

    The objective of this study is to determine the efficacy of adding a prokinetic agent to proton pump inhibitors (PPI) for the treatment of laryngopharyngeal reflux (LPR) disease. A prospective, randomized open trial comparing lansoprazole plus itopride to lansoprazole single therapy was performed for 12 weeks. Sixty-four patients with a reflux finding score (RFS) >7 and a reflux symptom index (RSI) >13 were enrolled and received either lansoprazole 30 mg once daily with itopride 50 mg three times daily or lansoprazole 30 mg once daily for 12 weeks. RSI and RFS were completed at baseline, after 6 weeks, and after 12 weeks. During the treatment period, RSI and RFS were significantly improved compared with the pretreatment scores in both study groups. Reductions of total RSI and globus symptom were significantly higher in the lansoprazole plus itopride group compared to the lansoprazole group. In the RFS, however, there were no significant differences between the two groups. In conclusion, itopride in addition to PPI did not show any superior RFS improvement compared to PPI single therapy, but was helpful in speeding up relief of reflux symptoms in LPR patients. Thus, itopride may be considered as the secondary additive agent in the PPI treatment of LPR patients.

  2. Comparison of betaxolol, a new beta 1-adrenergic antagonist, to propranolol in the treatment of mild to moderate hypertension.

    Davidov, M E; Glazer, N; Wollam, G; Zager, P G; Cangiano, J

    1988-07-01

    A double-blind, multicenter study compared the safety and efficacy of oral betaxolol 10 to 40 mg once daily (n = 68) with propranolol 40 to 160 mg twice daily (n = 73) in the treatment of mild to moderate essential hypertension. Both agents produced significant (P less than 0.01) and comparable reductions in mean supine systolic and diastolic blood pressures (7/11 mm Hg on betaxolol and 9/10 mm Hg on propranolol). Both betaxolol and propranolol significantly (P less than 0.01) reduced mean supine heart rate by 9 beats per minute. Patients achieved a more significant (P less than 0.01) reduction in blood pressure earlier (weeks 2 and 4 of the titration period) with betaxolol. By the end of treatment there was no significant difference in response between treatment groups. A higher incidence of central nervous system side effects (insomnia, bizarre dreams, depression, hallucinations, dizziness), however, was seen with propranolol than with betaxolol. Overall, the data show that in patients with mild to moderate essential hypertension, betaxolol 10 to 40 mg administered once daily is as effective as and better tolerated than propranolol 40 to 160 mg administered twice daily.

  3. Atenolol versus pindolol: side-effects in hypertension.

    Foerster, E C; Greminger, P; Siegenthaler, W; Vetter, H; Vetter, W

    1985-01-01

    This randomized crossover out-patient study was designed to compare the antihypertensive effects of atenolol and pindolol. After a wash-out period of two weeks in pretreated cases, 107 patients with essential hypertension were given either atenolol 100 mg once-daily or pindolol 20 mg slow release (SR) once-daily. Both atenolol and pindolol lowered blood pressure over the 24 week period. The diastolic blood pressure reduction was significantly greater (p less than 0.01) with atenolol than with pindolol. Before beta-blocker therapy, many patients had already experienced side-effects such as fatigue, sleep disturbances and dreams. This probably relates to the high sensitivity of the analogue scale used to assess side-effects, and to the high incidence of such symptoms in untreated patients. As the study progressed there was a reduction in the frequency of fatigue (p less than 0.03) and dreams (p less than 0.05) in both groups, whereas sleep disturbances significantly increased under pindolol (p less than 0.05) but decreased under atenolol (p less than 0.05). The only important side-effect difference between the two beta-blockers was the higher incidence of sleep disturbances with pindolol which may be due to the higher lipophilicity of this beta-blocker.

  4. The Efficacy of Reduced-dose Dasatinib as a Subsequent Therapy in Patients with Chronic Myeloid Leukemia in the Chronic Phase: The LD-CML Study of the Kanto CML Study Group

    Iriyama, Noriyoshi; Ohashi, Kazuteru; Hashino, Satoshi; Kimura, Shinya; Nakaseko, Chiaki; Takano, Hina; Hino, Masayuki; Uchiyama, Michihiro; Morita, Satoshi; Sakamoto, Junichi; Sakamaki, Hisashi; Inokuchi, Koiti

    2017-01-01

    Objective The aim of this study was to prospectively investigate the efficacy and safety profiles of low-dose dasatinib therapy (50 mg once daily). Methods Patients with chronic myeloid leukemia in the chronic phase (CML-CP) who were being treated with low-dose imatinib (≤200 mg/day), but were resistant to this agent were enrolled in the current study (referred to as the LD-CML study). Results There subjects included 9 patients (4 men and 5 women); all were treated with dasatinib at a dose of 50 mg once daily. Among 8 patients who had not experienced major molecular response (MMR; BCR-ABL1 transcript ≤0.1% according to International Scale [IS]) at study enrollment, 5 attained MMR by 12 months. In particular, 3 of 9 patients demonstrated a deep molecular response (DMR; IS ≤0.0069%) by 18 months. Five patients developed lymphocytosis accompanied by cytotoxic lymphocyte predominance. There was no mortality or disease progression, and all continue to receive dasatinib therapy at 18 months with only 2 patients requiring dose reduction. Toxicities were mild-to-moderate, and pleural effusion was observed in 1 patient (grade 1). Conclusion Low-dose dasatinib can attain MMR and DMR without severe toxicity in patients with CML-CP who are unable to achieve MMR with low-dose imatinib. Switching to low-dose dasatinib should therefore be considered for patients in this setting, especially if they are otherwise considering a cessation of treatment. PMID:29033428

  5. Site-specific fatty chain-modified exenatide analogs with balanced glucoregulatory activity and prolonged in vivo activity.

    Sun, Lidan; Huang, Xun; Han, Jing; Cai, Xingguang; Dai, Yuxuan; Chu, Yingying; Wang, Chuandong; Huang, Wenlong; Qian, Hai

    2016-06-15

    The therapeutic utility of exenatide (Ex-4) is limited due to short plasma half-life of 2.4h and thus numerous approaches have been used to obtain a longer action time. However, such strategies often attend to one thing and lose another. The study aimed to identify a candidate with balanced glucoregulatory activity and prolonged in vivo activity. A series of fatty chain conjugates of Ex-4 were designed and synthesized. First, thirteen cysteine modified peptides (1-13) were prepared. Peptides 1, 10, and 13 showed improved glucagon-like peptide-1 (GLP-1) receptor activate potency and were thus selected for second step modifications to yield conjugates I-1-I-9. All conjugates retained significant GLP-1 receptor activate potency and more importantly exerted enhanced albumin-binding properties and in vitro plasma stability. The protracted antidiabetic effects of the most stable I-3 were further confirmed by both multiple intraperitoneal glucose tolerance test and hypoglycemic efficacies test in vivo. Furthermore, once daily injection of I-3 to streptozotocin (STZ) induced diabetic mice achieved long-term beneficial effects on hemoglobin A1C (HbA1C) lowering and glucose tolerance. Once daily injection of I-3 to diet induced obesity (DIO) mice also achieved favorable effects on food intake, body weight, and blood chemistry. Our results suggested that I-3 was a promising agent deserving further investigation to treat obesity patients with diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Effect of Glycine on Lead Mobilization, Lead-Induced Oxidative Stress, and Hepatic Toxicity in Rats

    Yolanda Alcaraz-Contreras

    2011-01-01

    Full Text Available The effectiveness of glycine in treating experimental lead intoxication was examined in rats. Male Wistar rats were exposed to 3 g/L lead acetate in drinking water for 5 weeks and treated thereafter with glycine (100 and 500 mg/kg, orally once daily for 5 days or glycine (1000 mg/kg, orally once daily for 28 days. The effect of these treatments on parameters indicative of oxidative stress (glutathione and malondialdehyde levels, the activity of blood -aminolevulinic acid dehydratase, and lead concentration in blood, liver, kidney, brain, and bone were investigated. Liver samples were observed for histopathological changes. Glycine was found to be effective in (1 increasing glutathione levels; (2 reducing malondialdehyde levels; (3 decreasing lead levels in bone with the highest dose. However, glycine had no effect on lead mobilization when 100 and 500 mg/kg glycine were administered. In microscopic examination, glycine showed a protective effect against lead intoxication.

  7. Repeated Treatments with Ingenol Mebutate Prevents Progression of UV-Induced Photodamage in Hairless Mice

    Erlendsson, Andrés Már; Thaysen-Petersen, Daniel; Bay, Christiane

    2016-01-01

    BACKGROUND AND AIM: Ingenol mebutate (IngMeb) is an effective treatment for actinic keratosis. In this study, we hypothesized that repeated treatments with IngMeb may prevent progression of UV-induced photodamage, and that concurrent application of a corticosteroid may reduce IngMeb-induced local...... once daily for 5 days prior to each IngMeb application, as well as 6 h and 1 day post treatment. One week after IngMeb treatment No. 1, 3, and 5 (Days 28, 84, and 140), biopsies from four mice in each group were collected for histological evaluation of UV-damage on a standardized UV-damage scale (0......-12). LSR (0-24) were assessed once daily (Days 1-7) after each IngMeb treatment. RESULTS: IngMeb prevented progression of photodamage in terms of keratosis grade, epidermal hypertrophy, dysplasia, and dermal actinic damage with a lower composite UV-damage score on day 140 (UVR 10.25 vs. UVR+IngMeb 6.00, p...

  8. Ingenol mebutate gel for actinic keratosis: the link between quality of life, treatment satisfaction, and clinical outcomes.

    Augustin, Matthias; Tu, John H; Knudsen, Kim Mark; Erntoft, Sandra; Larsson, Thomas; Hanke, C William

    2015-05-01

    Actinic keratosis therapy can elicit unsightly and painful local skin responses; assessment of treatment satisfaction and health-related quality of life (QoL) is important. Ingenol mebutate gel is a novel topical field therapy for actinic keratosis. Post-hoc analyses were performed based on patient-reported outcomes from phase-III trials (n = 1005) to assess the effects of ingenol mebutate on QoL and the relationship between both QoL and treatment satisfaction, and degree of lesion clearance. Patients received ingenol mebutate or vehicle for self-application to a 25-cm(2) contiguous area: 0.015% once daily for 3 consecutive days (face/scalp) or 0.05% once daily for 2 consecutive days (trunk/extremities). QoL (Skindex-16) and Treatment Satisfaction Questionnaire for Medication data were recorded. Significant, positive associations between Treatment Satisfaction Questionnaire for Medication score and degree of clearance were identified for patients in the face/scalp (effectiveness P keratosis lesion clearance. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  9. Phase I Studies of Acebilustat: Pharmacokinetics, Pharmacodynamics, Food Effect, and CYP3A Induction.

    Elborn, J S; Bhatt, L; Grosswald, R; Ahuja, S; Springman, E B

    2017-01-01

    Acebilustat is a new once-daily oral antiinflammatory drug in development for treatment of cystic fibrosis (CF) and other diseases. It is an inhibitor of leukotriene A4 hydrolase; therefore, production of leukotriene B4 (LTB4) in biological fluids provides a direct measure of the pharmacodynamic (PD) response to acebilustat treatment. Here we compare the pharmacokinetics (PK) and PD between CF patients and healthy volunteers, and investigate the food effect and CYP3A4 induction in healthy volunteers. No significant differences between study populations were observed for peak plasma level (C max ) or exposure (AUC). In healthy volunteers, a shift in time to C max (T max ) was observed after a high-fat meal, but there was no change in AUC. LTB4 production was reduced in the blood of both populations and in sputum from CF patients. Acebilustat did not induce CYP3A4. These results support continued clinical study of once-daily oral acebilustat in CF at doses of 50 and 100 mg. © 2016 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  10. New developments in the combination treatment of COPD: focus on umeclidinium/vilanterol

    Cazzola M

    2013-10-01

    Full Text Available Mario Cazzola,1 Andrea Segreti,1 Maria Gabriella Matera2 1Department of System Medicine, University of Rome 'Tor Vergata', Rome, Italy; 2Department of Experimental Medicine, Second University, Naples, Italy Abstract: An increasing body of evidence suggests that the long-acting muscarinic antagonist (LAMA/long-acting β2-agonist (LABA combination appears to play an important role in maximizing bronchodilation, with studies to date indicating that combining different classes of bronchodilators may result in significantly greater improvements in lung function compared to the use of a single drug, and that these combinations are well tolerated in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD. An inhaled, fixed-dose combination of two 24-hour bronchodilators, the LAMA umeclidinium and the LABA vilanterol, is under development as a once-daily treatment for COPD. The efficacy of both mono-components has already been demonstrated. The information currently available suggests that umeclidinium/vilanterol is an effective once-daily dual bronchodilator fixed-dose combination in the treatment of COPD. However, it remains to be seen if it compares favorably with current therapies. Moreover, the question remains whether umeclidinium/vilanterol fixed-dose combination, which significantly improves FEV1, is also associated with improvements in other outcome measures that are important to COPD patients. Keywords: muscarinic antagonist, dual bronchodilation, COPD

  11. Evaluation of procedures for estimating ruminal particle turnover and diet digestibility in ruminant animals

    Cochran, R.C.

    1985-01-01

    Procedures used in estimating ruminal particle turnover and diet digestibility were evaluated in a series of independent experiments. Experiment 1 and 2 evaluated the influence of sampling site, mathematical model and intraruminal mixing on estimates of ruminal particle turnover in beef steers grazing crested wheatgrass or offered ad libitum levels of prairie hay once daily, respectively. Particle turnover rate constants were estimated by intraruminal administration (via rumen cannula) of ytterbium (Yb)-labeled forage, followed by serial collection of rumen digesta or fecal samples. Rumen Yb concentrations were transformed to natural logarithms and regressed on time. Influence of sampling site (rectum versus rumen) on turnover estimates was modified by the model used to fit fecal marker excretion curves in the grazing study. In contrast, estimated turnover rate constants from rumen sampling were smaller (P < 0.05) than rectally derived rate constants, regardless of fecal model used, when steers were fed once daily. In Experiment 3, in vitro residues subjected to acid or neutral detergent fiber extraction (IVADF and IVNDF), acid detergent fiber incubated in cellulase (ADFIC) and acid detergent lignin (ADL) were evaluated as internal markers for predicting diet digestibility. Both IVADF and IVNDF displayed variable accuracy for prediction of in vivo digestibility whereas ADL and ADFIC inaccurately predicted digestibility of all diets

  12. Development of a methodology to measure the effect of ergot alkaloids on forestomach motility using real-time wireless telemetry

    Egert, Amanda; Klotz, James; McLeod, Kyle; Harmon, David

    2014-10-01

    The objectives of these experiments were to characterize rumen motility patterns of cattle fed once daily using a real-time wireless telemetry system, determine when to measure rumen motility with this system, and determine the effect of ruminal dosing of ergot alkaloids on rumen motility. Ruminally cannulated Holstein steers (n = 8) were fed a basal diet of alfalfa cubes once daily. Rumen motility was measured by monitoring real-time pressure changes within the rumen using wireless telemetry and pressure transducers. Experiment 1 consisted of three 24-h rumen pressure collections beginning immediately after feeding. Data were recorded, stored, and analyzed using iox2 software and the rhythmic analyzer. All motility variables differed (P content samples were taken on d 15. Baseline (P = 0.06) and peak (P = 0.04) pressure were lower for E+ steers. Water intake tended (P = 0.10) to be less for E+ steers the first 8 hour period after feeding. The E+ seed treatment at this dosage under thermoneutral conditions did not significantly affect rumen motility, ruminal fill, or dry matter of rumen contents.

  13. Delayed-release oral suspension of omeprazole for the treatment of erosive esophagitis and gastroesophageal reflux disease in pediatric patients: a review

    Alice Monzani

    2010-03-01

    Full Text Available Alice Monzani, Giuseppina Oderda1Department of Pediatrics, Università del Piemonte Orientale, Novara, ItalyAbstract: Omeprazole is a proton-pump inhibitor indicated for gastroesophageal reflux disease and erosive esophagitis treatment in children. The aim of this review was to evaluate the efficacy of delayed-release oral suspension of omeprazole in childhood esophagitis, in terms of symptom relief, reduction in reflux index and/or intragastric acidity, and endoscopic and/or histological healing. We systematically searched PubMed, Cochrane and EMBASE (1990 to 2009 and identified 59 potentially relevant articles, but only 12 articles were suitable to be included in our analysis. All the studies evaluated symptom relief and reported a median relief rate of 80.4% (range 35%–100%. Five studies reported a significant reduction of the esophageal reflux index within normal limits (<7% in all children, and 4 studies a significant reduction of intra-gastric acidity. The endoscopic healing rate, reported by 9 studies, was 84% after 8-week treatment and 95% after 12-week treatment, the latter being significantly higher than the histological healing rate (49%. In conclusion, omeprazole given at a dose ranging from 0.3 to 3.5 mg/kg once daily (median 1 mg/kg once daily for at least 12 weeks is highly effective in childhood esophagitis.Keywords: proton pump inhibitors, children, ranitidine, H2-blockers

  14. [Effect of heat-reinforcing needling combined with rehabilitation training on the motor function of ischemic stroke patients].

    Zhang, Ning-xia; Liu, Gui-zhen; Huang, Tai-quan; Li, Wei-jiang; Luo, Jia-qi; Liu, Wei-wei; Huang, Yong; Wang, Ai-min

    2009-12-01

    To observe the therapeutic effect of heat-reinforcing needling combined with modem rehabilitation training on the motor function of ischemic stroke patients. Fifty case of ischemic stroke patients were randomly divided into rehabilitation (Rehab, n=40) and acupuncture (Acup) + Rehab (n=40) groups. Heat-reinforcing needling was applied to Jianyu (LI 15), Quchi (LI 11), Hegu (LI 14), Zusanli (ST 36), Yanglingquan (GB 34), Yinlingquan (SP 9) and Sanyinjiao (SP 6), once daily for 3 weeks. Rehabilitation training including healthy limb and joint movement was conducted, once daily for 3 weeks. The patient's neurological impairment degree and the motor function (Fugl-Meyer index) were evaluated before and after the treatment. After the treatment, of the each 40 cases in Rehab and Acup + Rehab groups, 10 (25.0%) and 17 (42.5%) experienced marked improvement in their symptoms, 17 (42.5%) and 18 (45.0%) had improvement, 13 (32.5%) and 5 (12.5%) failed, with the effective rates being 67.5% and 87.5% respectively. The therapeutic effect of Acup + Rehab group was markedly superior to that of Rehab group (P0.05). After the treatment, the scores of neurological impairment degree of two groups both decreased significantly (PRehab group was significantly lower than that of Rehab group (PRehab group were obviously higher than those of Rehab group (Pstroke patients.

  15. The Effect of Propolis in Healing Injured Nasal Mucosa: An Experimental Study

    El-Anwar, Mohammad Waheed; Abdelmonem, Said; Abdelsameea, Ahmed A.; AlShawadfy, Mohamed; El-Kashishy, Kamal

    2016-01-01

    Introduction  Mechanical trauma to the nasal mucosa increases the risk of synechia formation, especially after chronic rhinosinusitis and nasal surgeries. Objective  This study was carried to assess the effect of propolis administration in healing injured nasal mucosa in rats. Methods  We randomly divided eighteen rats into three equal experimental groups: (1) non-treated group; (2) gum tragacanth (suspending agent for propolis) treated group; and (3) propolis treated group. The non-treated group received no treatment for 15 days. The second group received gum tragacanth administration (5 ml/kg, orally) once daily for 15 days. The third group received propolis suspension orally at a dose of 100 mg/kg once daily for 15 days. At the beginning of this study, we induced unilateral mechanical nasal trauma on the right nasal mucosa of all rats in the three groups using a brushing technique. A pathologist stained tissue samples using hematoxylin and examined eosin by using a light microscope. Results  The severity of inflammation was milder with the absence of ulcerations in the propolis treated group compared with the non-treated and gum tragacanth groups. Goblet cell and ciliated cell loss was substantially lower in patients treated with propolis compared with groups without treatment and those treated with gum tragacanth. Conclusion  Propolis decreased inflammation and enhanced healing of wounds of the nasal mucosa in rats. PMID:27413403

  16. The Effect of Propolis in Healing Injured Nasal Mucosa: An Experimental Study

    El-Anwar, Mohammad Waheed

    2016-02-01

    Full Text Available Introduction Mechanical trauma to the nasal mucosa increases the risk of synechia formation, especially after chronic rhinosinusitis and nasal surgeries. Objective This study was carried to assess the effect of propolis administration in healing injured nasal mucosa in rats. Methods We randomly divided eighteen rats into three equal experimental groups: (1 non-treated group; (2 gum tragacanth (suspending agent for propolis treated group; and (3 propolis treated group. The non-treated group received no treatment for 15 days. The second group received gum tragacanth administration (5 ml/kg, orally once daily for 15 days. The third group received propolis suspension orally at a dose of 100 mg/kg once daily for 15 days. At the beginning of this study, we induced unilateral mechanical nasal trauma on the right nasal mucosa of all rats in the three groups using a brushing technique. A pathologist stained tissue samples using hematoxylin and examined eosin by using a light microscope. Results The severity of inflammation was milder with the absence of ulcerations in the propolis treated group compared with the non-treated and gum tragacanth groups. Goblet cell and ciliated cell loss was substantially lower in patients treated with propolis compared with groups without treatment and those treated with gum tragacanth. Conclusion Propolis decreased inflammation and enhanced healing of wounds of the nasal mucosa in rats.

  17. Ameliorative effect of Pimpinella anisum oil on immunohistochemical and ultrastuctural changes of cerebellum of albino rats induced by aspartame.

    Abdul-Hamid, Manal; Gallaly, Sanaa Rida

    2014-05-01

    The study aims to investigate the protective effect of Pimpinella anisum oil on aspartame (ASP) which resulted in cerebellar changes. The rats were divided into four equal groups: Group 1: (control group): served as control animals. Group 2: control P. anisum oil received .5 mL/kg/d/b wt. once daily. Group 3 (ASP group): received daily 250 mg/kg/b wt. of ASP dissolved in distilled water and given orally to the animals by intra-gastric tube for 2 months. Group 4: received .5 mL/kg/b wt. of prophylactic P. anisum oil once daily, followed by ASP after 2 h for 2 months. The histopathological approach revealed marked changes in the Purkinje cells, myleinated nerve fibers and granular cells of ASP-treated animals. Some of these cells appeared with deeply stained cytoplasm. Ultrastructural examination showed Purkinje cells with dilated rough endoplasmic reticulum and condensed mitochondria. Granular cells appeared with less c nuclei and surrounded by dissolution of most Mossy rosettes structures. Most myelinated nerve fibers showed thickening of myelinated sheath and others showed splitting of their myelin sheath. The histopathological, immunohistochemical and ultrastructural alterations were much less observed in concomitant use of P. anisum oil with ASP. Cerebellar cortex is considered target areas of ASP neurotoxicity, while P. anisum oil, when used in combination with ASP displays a protective action against neurotoxicity.

  18. The management of schizophrenia: focus on extended-release quetiapine fumarate

    Peuskens J

    2011-09-01

    Full Text Available Joseph Peuskens Universitair Psychiatrisch Centrum KU Leuven, Campus St Jozef Kortenberg, Kortenberg, Belgium Abstract: Effective management of schizophrenia remains a significant clinical challenge. While antipsychotic medications have proven efficacy in this disease, there remains an opportunity to further improve symptom control and long-term relapse prevention. Also, a number of factors, including tolerability and complex dosing regimens, can result in nonadherence to medication. Quetiapine is an atypical antipsychotic with proven efficacy and an established tolerability profile in schizophrenia. The once-daily extended-release formulation (quetiapine XR offers a simplified dosing regimen and titration schedule. Short-term clinical studies have shown that quetiapine XR (400–800 mg/d is efficacious in the acute treatment of schizophrenia, while a long-term study has shown that quetiapine XR was significantly more effective than placebo at preventing relapse. Furthermore, an investigation in which stable patients switched from the immediate-release formulation (quetiapine IR to quetiapine XR showed that quetiapine XR is generally well tolerated and has no loss of efficacy compared with quetiapine IR. In patients who experienced insufficient efficacy or poor tolerability on their previous antipsychotic, switching to quetiapine XR significantly improved efficacy compared with the previous treatment. In conclusion, quetiapine XR is an effective and generally well tolerated treatment for schizophrenia. Furthermore, once-daily dosing may improve patient adherence, which may impact positively on patient outcomes. Keywords: adherence, atypical antipsychotics, adverse events

  19. Regulatory challenges in developing long-acting antiretrovirals for treatment and prevention of HIV infection.

    Arya, Vikram; Au, Stanley; Belew, Yodit; Miele, Peter; Struble, Kimberly

    2015-07-01

    To outline some of the regulatory challenges inherent to the development of long-acting antiretrovirals (ARVs) for the treatment or prevention of HIV infection. Despite advances in drug development that have reduced ARV dosing to once daily, suboptimal drug adherence remains an obstacle to successful HIV treatment. Further, large randomized trials of once daily oral ARVs for preexposure prophylaxis (PrEP) have shown that drug adherence correlates strongly with prophylactic effect and study outcomes. Thus, the prospect of developing long-acting ARVs, which may mitigate drug adherence issues, has attracted considerable attention lately. Because of their pharmacokinetic properties, the development of long-acting ARVs can present novel regulatory challenges. Chief among them is determining the appropriate dosing regimen, the need for an oral lead-in, and whether existing data with an approved oral agent, if available, can be leveraged for a treatment or prevention indication. For PrEP, because validated biomarkers are lacking, additional nonclinical studies and evaluation of tissue concentrations in multiple compartments may be necessary to identify optimal dosages. Study design and choice of controls for registrational trials of new long-acting PrEP agents might also prove challenging following the availability of an oral PrEP drug.

  20. Pharmacokinetics and Pharmacodynamics with Extended Dosing of CC-486 in Patients with Hematologic Malignancies.

    Eric Laille

    Full Text Available CC-486 (oral azacitidine is an epigenetic modifier in development for patients with myelodysplastic syndromes and acute myeloid leukemia. In part 1 of this two-part study, a 7-day CC-486 dosing schedule showed clinical activity, was generally well tolerated, and reduced DNA methylation. Extending dosing of CC-486 beyond 7 days would increase duration of azacitidine exposure. We hypothesized that extended dosing would therefore provide more sustained epigenetic activity. Reported here are the pharmacokinetic (PK and pharmacodynamic (PD profiles of CC-486 extended dosing schedules in patients with myelodysplastic syndromes (MDS, chronic myelomonocytic leukemia (CMML or acute myeloid leukemia (AML from part 2 of this study. PK and/or PD data were available for 59 patients who were sequentially assigned to 1 of 4 extended CC-486 dosing schedules: 300mg once-daily or 200mg twice-daily for 14 or 21 days per 28-day cycle. Both 300mg once-daily schedules and the 200mg twice-daily 21-day schedule significantly (all P < .05 reduced global DNA methylation in whole blood at all measured time points (days 15, 22, and 28 of the treatment cycle, with sustained hypomethylation at cycle end compared with baseline. CC-486 exposures and reduced DNA methylation were significantly correlated. Patients who had a hematologic response had significantly greater methylation reductions than non-responding patients. These data demonstrate that extended dosing of CC-486 sustains epigenetic effects through the treatment cycle.ClinicalTrials.gov NCT00528983.

  1. Suboptimal Antituberculosis Drug Concentrations and Outcomes in Small and HIV-Coinfected Children in India: Recommendations for Dose Modifications.

    Guiastrennec, Benjamin; Ramachandran, Geetha; Karlsson, Mats O; Kumar, A K Hemanth; Bhavani, Perumal Kannabiran; Gangadevi, N Poorana; Swaminathan, Soumya; Gupta, Amita; Dooley, Kelly E; Savic, Radojka M

    2017-12-16

    This work aimed to evaluate the once-daily antituberculosis treatment as recommended by the new Indian pediatric guidelines. Isoniazid, rifampin, and pyrazinamide concentration-time profiles and treatment outcome were obtained from 161 Indian children with drug-sensitive tuberculosis undergoing thrice-weekly dosing as per previous Indian pediatric guidelines. The exposure-response relationships were established using a population pharmacokinetic-pharmacodynamic approach. Rifampin exposure was identified as the unique predictor of treatment outcome. Consequently, children with low body weight (4-7 kg) and/or HIV infection, who displayed the lowest rifampin exposure, were associated with the highest probability of unfavorable treatment (therapy failure, death) outcome (P unfavorable ). Model-based simulation of optimized (P unfavorable ≤ 5%) rifampin once-daily doses were suggested per treatment weight band and HIV coinfection status (33% and 190% dose increase, respectively, from the new Indian guidelines). The established dose-exposure-response relationship could be pivotal in the development of future pediatric tuberculosis treatment guidelines. © 2017, The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  2. NEBIVOLOL IN TREATMENT OF STABLE EXERTIONAL ANGINA PECTORIS

    Y. V. Gavrilov

    2015-12-01

    Full Text Available Aim. To evaluate antianginal and antiischemic efficiency of nebivolol in patients with stable angina pectoris.Material and methods. 100 patients with ischemic heart disease showing stable exertional angina pectoris and having no contraindications to beta-blockers were studied. After 5-7 days of control period 50 randomly selected patients began to take nebivolol in initial dose of 5mg once daily and 50 patients started to take metoprolol in initial dose of 50 mg twice daily. Duration of treatment was 8 weeks. Efficiency of treatment was assessed according to the results of control treadmill assessment and control daily ECG monitoring.Results. 56-day therapy with nebivolol at a dose of 7,5 mg per day results in increase in duration of treadmill test before angina or ST depression (p<0.05. Antianginal and antiischemic effect of nebivolol 7.5 mg once daily is rather similar with that of metoprolol in average daily dose of 175 mg. Nebivolol compared to metoprolol significantly (p<0.05 more effectively reduces the number of silent myocardial ischemia.Conclusion. Nebivolol is an efficient antianginal and antiischemic drug for patients with stable exertional angina pectoris.

  3. Amnesia induced by morphine in spatial memory retrieval inhibited in morphine-sensitized rats.

    Farahmandfar, Maryam; Naghdi, Nasser; Karimian, Seyed Morteza; Kadivar, Mehdi; Zarrindast, Mohammad-Reza

    2012-05-15

    The present study investigated the effect of morphine sensitization on the impairment of spatial memory retrieval induced by acute morphine in adult male rats. Spatial memory was assessed by 2-day Morris water maze task which included training and test day. On the training day, rats were trained by a single training session of 8 trials. On the test day, a probe trial consisting of 60s free swim period without a platform and the visible test were administered. Morphine sensitization was induced by subcutaneous (s.c.) injection of morphine, once daily for 3 days followed by 5 days without drug treatment before training. The results indicated that acute administration of morphine (7.5mg/kg, s.c.) before testing impaired spatial memory on the test day. Pre-test morphine-induced amnesia decreased in morphine-sensitized (15 and 20mg/kg, s.c.) rats. Improvement in spatial memory retrieval in morphine-sensitized rats was inhibited by once daily administration of naloxone (1 and 2mg/kg, s.c.) 30 min prior to the injection of morphine for three days. The results suggest that morphine sensitization reverses the impairment of spatial memory retrieval induced by acute morphine and it is implied that mu-opioid receptors may play an important role in this effect. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Acute Phase Proteins in Response to Dictyocaulus viviparus Infection in Calves

    Waller K Persson

    2004-06-01

    Full Text Available Three experiments were carried out to examine the acute phase response, as measured by the acute phase proteins (APP haptoglobin, serum amyloid A (SAA and fibrinogen, in calves infected with lungworm, Dictyocaulus vivparus. In addition, eosinophil counts were analysed. Three different dose models were used in 3 separate experiments: I 250 D. viviparus infective third stage larvae (L3 once daily for 2 consecutive days, II 100 D. viviparus L3 once daily for 5 consecutive days, and III 2000 L3 once. All 3 dose regimes induced elevated levels of haptoglobin, SAA and fibrinogen, although there was considerable variation both between and within experiments. A significant increase was observed in all 3 APP at one or several time points in experiment I and III, whereas in experiment II, the only significant elevation was observed for fibrinogen at one occasion. The eosinophil numbers were significantly elevated in all 3 experiments. The results show that lungworm infection can induce an acute phase response, which can be monitored by the selected APP. Elevated APP levels in combination with high numbers of eosinophils in an animal with respiratory disease may be used as an indicator of lung worm infection, and help the clinician to decide on treatment. However, high numbers of eosinophils and low levels of APP do not exclude a diagnosis of lungworm. Thus, lungworm infection may not be detected if measurements of APP are used to assess calf health in herds or individual animals.

  5. Liver, but not muscle, has an entrainable metabolic memory.

    Sheng-Song Chen

    Full Text Available Hyperglycemia in the hospitalized setting is common, especially in patients that receive nutritional support either continuously or intermittently. As the liver and muscle are the major sites of glucose disposal, we hypothesized their metabolic adaptations are sensitive to the pattern of nutrient delivery. Chronically catheterized, well-controlled depancreatized dogs were placed on one of three isocaloric diets: regular chow diet once daily (Chow or a simple nutrient diet (ND that was given either once daily (ND-4 or infused continuously (ND-C. Intraportal insulin was infused to maintain euglycemia. After 5 days net hepatic (NHGU and muscle (MGU glucose uptake and oxidation were assessed at euglycemia (120 mg/dl and hyperglycemia (200 mg/dl in the presence of basal insulin. While hyperglycemia increased both NHGU and MGU in Chow, NHGU was amplified in both groups receiving ND. The increase was associated with enhanced activation of glycogen synthase, glucose oxidation and suppression of pyruvate dehydrogenase kinase-4 (PDK-4. Accelerated glucose-dependent muscle glucose uptake was only evident with ND-C. This was associated with a decrease in PDK-4 expression and an increase in AMP-activated protein kinase (AMPK phosphorylation. Interestingly, ND-C markedly increased hepatic FGF-21 expression. Thus, augmentation of carbohydrate disposal in the liver, as opposed to the muscle, is not dependent on the pattern of nutrient delivery.

  6. Randomized Phase III and Extension Studies of Naldemedine in Patients With Opioid-Induced Constipation and Cancer.

    Katakami, Nobuyuki; Harada, Toshiyuki; Murata, Toru; Shinozaki, Katsunori; Tsutsumi, Masakazu; Yokota, Takaaki; Arai, Masatsugu; Tada, Yukio; Narabayashi, Masaru; Boku, Narikazu

    2017-12-01

    Purpose Opioid-induced constipation (OIC) is a frequent and debilitating adverse effect (AE) of opioids-common analgesics for cancer pain. We investigated the efficacy and safety of a peripherally acting μ-opioid receptor antagonist, naldemedine (S-297995), for OIC, specifically in patients with cancer. Patients and Methods This phase III trial consisted of a 2-week, randomized, double-blind, placebo-controlled study (COMPOSE-4) and an open-label, 12-week extension study (COMPOSE-5). In COMPOSE-4, eligible adults with OIC and cancer were randomly assigned on a 1:1 basis to receive once-daily oral naldemedine 0.2 mg or placebo. The primary end point was the proportion of spontaneous bowel movement (SBM) responders (≥ 3 SBMs/week and an increase of ≥ 1 SBM/week from baseline). The primary end point of COMPOSE-5 was safety. Results In COMPOSE-4, 193 eligible patients were randomly assigned to naldemedine (n = 97) or placebo (n = 96). The proportion of SBM responders in COMPOSE-4 was significantly greater with naldemedine than with placebo (71.1% [69 of 97 patients] v 34.4% [33 of 96 patients]; P opioid withdrawal and had no notable impact on opioid-mediated analgesia. Conclusion Once-daily oral naldemedine 0.2 mg effectively treated OIC and was generally well tolerated in patients with OIC and cancer.

  7. Efficacy and safety of oral alitretinoin in severe oral lichen planus--results of a prospective pilot study.

    Kunz, M; Urosevic-Maiwald, M; Goldinger, S M; Frauchiger, A L; Dreier, J; Belloni, B; Mangana, J; Jenni, D; Dippel, M; Cozzio, A; Guenova, E; Kamarachev, J; French, L E; Dummer, R

    2016-02-01

    Patients with severe oral lichen planus refractory to standard topical treatment currently have limited options of therapy suitable for long-term use. Oral alitretinoin (9-cis retinoic acid) was never systematically investigated in clinical trials, although case reports suggest its possible efficacy. To assess the efficacy and safety of oral alitretinoin taken at 30 mg once daily for up to 24 weeks in the treatment of severe oral lichen planus refractory to standard topical therapy. We conducted a prospective open-label single arm pilot study to test the efficacy and safety of 30 mg oral alitretinoin once daily for up to 24 weeks in severe oral lichen planus. Ten patients were included in the study. Primary end point was reduction in signs and symptoms measured by the Escudier severity score. Secondary parameters included pain and quality of life scores. Safety parameters were assessed during a follow-up period of 5 weeks. A substantial response at the end of treatment, i.e. >50% reduction in disease severity measured by the Escudier severity score, was apparent in 40% of patients. Therapy was well tolerated. Adverse events were mild and included headache, mucocutaneous dryness, musculoskeletal pain, increased thyroid-stimulating hormone and dyslipidaemia. Alitretinoin given at 30 mg daily reduced disease severity of severe oral lichen planus in a substantial proportion of patients refractory to standard treatment, was well tolerated and may thus represent one therapeutic option for this special group of patients. © 2015 European Academy of Dermatology and Venereology.

  8. Toothbrushing frequency among 4–6-year-old Iranian children and associated maternal attitude and sociobehavioral factors

    Soltani, Raheleh; Eslami, Ahmad Ali; Akhlaghi, Najmeh; Sharifirad, Gholamreza; Alipoor, Mikaeil; Mahaki, Behzad

    2017-01-01

    Background: Toothbrushing is an important aspect of children's oral health self-care. This study aimed to explore toothbrushing frequency among 4–6-year-old Iranian children and associated maternal attitude and sociobehavioral factors. Materials and Methods: This cross-sectional study was conducted on 407 mother–child (aged 4–6 years) pairs through stratified random sampling in Tabriz, Iran. Data were collected using self-reported questionnaires including demographic characteristic, maternal attitude, and toothbrushing frequency of both mothers and children. Logistic regression was used to determine the predicators of children's toothbrushing. Statistical significance was set at P brushed their teeth once daily. Nearly 38.7% of children started toothbrushing behavior regularly at 4 years of age, and 41% had dental visits. Multiple logistic regression analysis indicated that children's toothbrushing (once daily or more) was associated with maternal brushing frequency (odds ratio [OR] =2.0, 95% confidence interval [CI] =1.53–2.86), maternal attitude toward oral health (OR = 1.15, CI = 1.08–1.22), and children's age (OR = 1.21, 95% CI = 1.02–1.77). Conclusion: The descriptive results indicated that maternal and children toothbrushing behaviors are unfavorable. Furthermore, maternal toothbrushing behavior is a strong predicator of children's brushing behavior. Health promotional activities seem necessary for mothers to enhance oral health behavior of their children. PMID:28348618

  9. Oral hygiene habits, dental home, and toothbrushing among immigrant and native low socioeconomic class populations.

    Davidovich, E; Kooby, E; Shapira, J; Ram, D

    2013-01-01

    About 45,000 people immigrated to Israel from Ethiopia over the last 30 years. The purpose of this study was to compare oral hygiene habits in preschool children from low socioeconomic neighborhoods offspring of immigrants from Ethiopia to offspring of native Israelis. Parents of children attending 21 nursery schools were asked to respond anonymously to 7 questions about their children's visits to a dentist and toothbrushing habits. Parents of 719 children (382 Ethiopian and 337 native Israeli) responded. Of children aged 49-82 months, 15% offspring of Ethiopian and 25% of native Israelis were reported to have visited a dentist; and 45% and 65%, respectively, to brush their teeth at least once daily. More than 90% of children of both populations were reported to have toothbrushes. Of children aged 18-48 months, 28% of Ethiopian and 65% of native Israelis were reported to brush their teeth at least once daily. After more than 20 years residence in a new country, the dental home of an immigrant population was significantly different from that of the native population, of the same low socioeconomic neighborhoods. Discrepancies in parental responses highlight the importance of addressing information bias.

  10. Pan-FGFR inhibition leads to blockade of FGF23 signaling, soft tissue mineralization, and cardiovascular dysfunction.

    Yanochko, Gina M; Vitsky, Allison; Heyen, Jonathan R; Hirakawa, Brad; Lam, Justine L; May, Jeff; Nichols, Tim; Sace, Frederick; Trajkovic, Dusko; Blasi, Eileen

    2013-10-01

    The fibroblast growth factor receptors (FGFR) play a major role in angiogenesis and are desirable targets for the development of therapeutics. Groups of Wistar Han rats were dosed orally once daily for 4 days with a small molecule pan-FGFR inhibitor (5mg/kg) or once daily for 6 days with a small molecule MEK inhibitor (3mg/kg). Serum phosphorous and FGF23 levels increased in all rats during the course of the study. Histologically, rats dosed with either drug exhibited multifocal, multiorgan soft tissue mineralization. Expression levels of the sodium phosphate transporter Npt2a and the vitamin D-metabolizing enzymes Cyp24a1 and Cyp27b1 were modulated in kidneys of animals dosed with the pan-FGFR inhibitor. Both inhibitors decreased ERK phosphorylation in the kidneys and inhibited FGF23-induced ERK phosphorylation in vitro in a dose-dependent manner. A separate cardiovascular outcome study was performed to monitor hemodynamics and cardiac structure and function of telemetered rats dosed with either the pan-FGFR inhibitor or MEK inhibitor for 3 days. Both compounds increased blood pressure (~+ 17 mmHg), decreased heart rate (~-75 bpm), and modulated echocardiography parameters. Our data suggest that inhibition of FGFR signaling following administration of either pan-FGFR inhibitor or MEK inhibitor interferes with the FGF23 pathway, predisposing animals to hyperphosphatemia and a tumoral calcinosis-like syndrome in rodents.

  11. Two doses of rivaroxaban versus aspirin for prevention of recurrent venous thromboembolism. Rationale for and design of the EINSTEIN CHOICE study.

    Weitz, Jeffrey I; Bauersachs, Rupert; Beyer-Westendorf, Jan; Bounameaux, Henri; Brighton, Timothy A; Cohen, Alexander T; Davidson, Bruce L; Holberg, Gerlind; Kakkar, Ajay; Lensing, Anthonie W A; Prins, Martin; Haskell, Lloyd; van Bellen, Bonno; Verhamme, Peter; Wells, Philip S; Prandoni, Paolo

    2015-08-31

    Patients with unprovoked venous thromboembolism (VTE) are at high risk for recurrence. Although rivaroxaban is effective for extended VTE treatment at a dose of 20 mg once daily, use of the 10 mg dose may further improve its benefit-to-risk ratio. Low-dose aspirin also reduces rates of recurrent VTE, but has not been compared with anticoagulant therapy. The EINSTEIN CHOICE study is a multicentre, randomised, double-blind, active-controlled, event-driven study comparing the efficacy and safety of two once daily doses of rivaroxaban (20 and 10 mg) with aspirin (100 mg daily) for the prevention of recurrent VTE in patients who completed 6-12 months of anticoagulant therapy for their index acute VTE event. All treatments will be given for 12 months. The primary efficacy objective is to determine whether both doses of rivaroxaban are superior to aspirin for the prevention of symptomatic recurrent VTE, while the principal safety outcome is the incidence of major bleeding. The trial is anticipated to enrol 2,850 patients from 230 sites in 31 countries over a period of 27 months. In conclusion, the EINSTEIN CHOICE study will provide new insights into the optimal antithrombotic strategy for extended VTE treatment by comparing two doses of rivaroxaban with aspirin (clinicaltrials.gov NCT02064439).

  12. Daily Administration of Short-Acting Liothyronine Is Associated with Significant Triiodothyronine Excursions and Fails to Alter Thyroid-Responsive Parameters.

    Jonklaas, Jacqueline; Burman, Kenneth D

    2016-06-01

    Although most studies of levothyroxine-liothyronine combination therapy employ once-daily hormone administration, the kinetics of once-daily liothyronine have been studied infrequently. The aim of this study was to document both the peak and trough serum triiodothyronine (T3) levels that occur with once-daily liothyronine administration, along with changes in thyroid-responsive parameters. Participants with hypothyroidism were studied prospectively at an academic institution. Patients were switched from levothyroxine monotherapy to liothyronine monotherapy with 15 μg liothyronine for two weeks, and then continued liothyronine at doses of 30-45 μg for a further four weeks in an open-label, single-arm study. Weekly trough levels of T3 were documented. In addition, hourly T3 concentrations immediately following liothyronine tablet administration were documented for eight hours during the sixth week of therapy. Serum thyrotropin (TSH) and free thyroxine (fT4) concentrations were documented. Biochemical markers, markers of energy metabolism, anthropometric parameters, well-being, and hyperthyroid symptoms were also assessed. Mean serum TSH levels increased from 1.56 ± 0.81 mIU/L at baseline to 5.90 ± 5.74 mIU/L at two weeks and 3.84 ± 3.66 mIU/L at six weeks. Trough T3 levels decreased from 99.5 ± 22.9 to 91.9 ± 40.2 at two weeks and recovered to 96.1 ± 32.2 at six weeks. The peak T3 concentration after dosing of liothyronine during week 6 was 292.8 ± 152.3 ng/dL. fT4 levels fell once levothyroxine was discontinued and plateaued at 0.44 ng/dL at week 4. The sex hormone binding globulin (SHBG) concentration decreased at week 2 (p = 0.002). Hyperthyroid symptoms and SF36-PCS scores increased significantly at weeks 4-5 of liothyronine therapy (p = 0.04-0.005). Preference for liothyronine therapy increased from 6% to 39% over the study period. Once-daily dosing of liothyronine at doses of 30-45 μg did not return serum

  13. Duloxetine: a review of its use in the treatment of generalized anxiety disorder.

    Carter, Natalie J; McCormack, Paul L

    2009-01-01

    Duloxetine (Cymbalta(R)) is a potent serotonin and noradrenaline (norepinephrine) reuptake inhibitor (SNRI) in the CNS. It is indicated for the treatment of generalized anxiety disorder (GAD) as well as other indications. In patients with GAD of at least moderate severity, oral duloxetine 60-120 mg once daily was effective with regard to improvement from baseline in assessments of anxiety and functional impairment, and numerous other clinical endpoints. Longer-term duloxetine 60-120 mg once daily also demonstrated efficacy in preventing or delaying relapse in responders among patients with GAD. In addition, duloxetine was generally well tolerated, with most adverse events being of mild to moderate severity in patients with GAD in short- and longer-term trials. Additional comparative and pharmacoeconomic studies are required to position duloxetine among other selective serotonin reuptake inhibitors and SNRIs. However, available clinical data, and current treatment guidelines, indicate that duloxetine is an effective first-line treatment option for the management of GAD. Duloxetine is a potent and selective inhibitor of serotonin and noradrenaline transporters, and a weak inhibitor of dopamine transporters. It has a low affinity for neuronal receptors, such as alpha(1)- and alpha(2)-adrenergic, dopamine D(2), histamine H(1), muscarinic, opioid and serotonin receptors, as well as ion channel binding sites and other neurotransmitter transporters, such as choline and GABA transporters. It does not inhibit monoamine oxidase types A or B. The pharmacokinetics of duloxetine in healthy volunteers were dose proportional over the range of 40-120 mg once daily. Steady state was typically reached by day 3 of administration. Duloxetine may be administered without regard to food or time of day. Duloxetine is highly protein bound and is widely distributed throughout tissues. It is rapidly and extensively metabolized in the liver by cytochrome P450 (CYP) 1A2 and 2D6, and its

  14. Feeding motivation and plasma metabolites in pregnant sows fed diets rich in dietary fiber either once or twice daily.

    Jensen, M B; Pedersen, L J; Theil, P K; Yde, C C; Bach Knudsen, K E

    2012-06-01

    The present study investigated the effects of source and level of dietary fiber (DF) and feeding frequency (once vs. twice daily) on feeding motivation and plasma metabolites at 4 different time points post feeding. Sixty pregnant sows (Sus scrofa, 4 blocks of 15 sows) were allocated to 1 of 5 diets within blocks. Four diets were restricted (approximately 35 MJ ME/d): a barley and wheat control diet (171 g DF/kg DM; 12 g DF/MJ ME), and 3 fiber diets formulated to contain 35% DF by including pectin residue (323 g DF/kg DM; 25 g DF/MJ ME), potato pulp (404 g DF/kg DM; 29 g DF/MJ ME), or sugar beet pulp (367 g DF/kg DM; 25 g DF/MJ ME). The fifth diet was a mixture including an equal amount of the 3 fiber diets offered semi ad libitum (ad libitum access to feed during 6 periods of 1 h starting at 0300, 0600, 1100, 1500, 1800, and 2300; 354 g DF/kg DM; 25 g DF/MJ ME). The experimental period included 2 periods of 4 wk each. Restricted-fed sows were fed once daily (0800 h) during the first period and twice daily (0800 and 1500 h) during the second period, or vice versa. Semi ad libitum fed sows had access to feed 6 times a day in both periods. In each period, the feeding motivation was assessed in an operant conditioning test, and samples of peripheral blood were taken in a balanced design, at 0900, 1200, 1900, and 0700 h, corresponding to 1, 4, 11, and 23 h after feeding for restricted sows fed once daily. No differences in the feeding motivation were found between the 4 restricted diets at any of the time points post feeding, but semi ad libitum fed sows had a decreased feeding motivation (P motivation at 1900 h (P motivation during the night compared with feeding once daily. Among restricted-fed sows, plasma concentrations of short-chain fatty acids (SCFA) were greater in sows fed high-fiber diets compared with the control (P = 0.02). Nonesterified fatty acid was least in sows on the control diet and greatest in sows on the potato diet, whereas sows on the pectin and

  15. Plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood and breast milk spots in nursing African mother–infant pairs

    Waitt, Catriona; Olagunju, Adeniyi; Nakalema, Shadia; Kyohaire, Isabella; Owen, Andrew; Lamorde, Mohammed; Khoo, Saye

    2018-01-01

    Abstract Background Breast milk transfer of first-line ART from mother to infant is not fully understood. Objectives To determine the concentrations of lamivudine, emtricitabine and tenofovir in maternal blood, breast milk and infant blood from breastfeeding mother–infant pairs. Methods Intensive pharmacokinetic sampling of maternal dried blood spots (DBS), dried breast milk spots (DBMS) and infant DBS from 30 Ugandan and 29 Nigerian mothers receiving first-line ART and their infants was conducted. DBS and DBMS were collected pre-dose and at 5–6 timepoints up to 12 h following observed dosing. Infant DBS were sampled twice during this period. Lamivudine, emtricitabine and tenofovir were quantified using LC-MS/MS, with non-compartmental analysis to calculate key pharmacokinetic parameters. Results Peak concentrations in breast milk from women taking lamivudine and emtricitabine occurred later than in plasma (4–8 h compared with 2 h for lamivudine and 2–4 h for emtricitabine). Consequently, the milk-to-plasma (M:P) ratio of lamivudine taken once daily was 0.95 (0.82–1.15) for AUC0–12, whereas for AUC12–20 this was 3.04 (2.87–4.16). Lamivudine was detectable in 36% (14/39) of infants [median 17.7 (16.3–22.7) ng/mL]. For 200 mg of emtricitabine once daily, the median M:P ratio was 3.01 (2.06–3.38). Three infants (19%) had measurable emtricitabine [median 18.5 (17.6–20.8) ng/mL]. For 300 mg of tenofovir once daily, the median M:P ratio was 0.015 (0–0.03) and no infant had measurable tenofovir concentrations. Conclusions Emtricitabine and lamivudine accumulate in breast milk and were detected in breastfeeding infants. In contrast, tenofovir penetrates the breast milk to a small degree, but is undetectable in breastfeeding infants. PMID:29309634

  16. Plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood and breast milk spots in nursing African mother-infant pairs.

    Waitt, Catriona; Olagunju, Adeniyi; Nakalema, Shadia; Kyohaire, Isabella; Owen, Andrew; Lamorde, Mohammed; Khoo, Saye

    2018-04-01

    Breast milk transfer of first-line ART from mother to infant is not fully understood. To determine the concentrations of lamivudine, emtricitabine and tenofovir in maternal blood, breast milk and infant blood from breastfeeding mother-infant pairs. Intensive pharmacokinetic sampling of maternal dried blood spots (DBS), dried breast milk spots (DBMS) and infant DBS from 30 Ugandan and 29 Nigerian mothers receiving first-line ART and their infants was conducted. DBS and DBMS were collected pre-dose and at 5-6 timepoints up to 12 h following observed dosing. Infant DBS were sampled twice during this period. Lamivudine, emtricitabine and tenofovir were quantified using LC-MS/MS, with non-compartmental analysis to calculate key pharmacokinetic parameters. Peak concentrations in breast milk from women taking lamivudine and emtricitabine occurred later than in plasma (4-8 h compared with 2 h for lamivudine and 2-4 h for emtricitabine). Consequently, the milk-to-plasma (M:P) ratio of lamivudine taken once daily was 0.95 (0.82-1.15) for AUC0-12, whereas for AUC12-20 this was 3.04 (2.87-4.16). Lamivudine was detectable in 36% (14/39) of infants [median 17.7 (16.3-22.7) ng/mL]. For 200 mg of emtricitabine once daily, the median M:P ratio was 3.01 (2.06-3.38). Three infants (19%) had measurable emtricitabine [median 18.5 (17.6-20.8) ng/mL]. For 300 mg of tenofovir once daily, the median M:P ratio was 0.015 (0-0.03) and no infant had measurable tenofovir concentrations. Emtricitabine and lamivudine accumulate in breast milk and were detected in breastfeeding infants. In contrast, tenofovir penetrates the breast milk to a small degree, but is undetectable in breastfeeding infants.

  17. Amikacin Dosing and Monitoring in Spinal Cord Injury Patients: Variation in Clinical Practice Between Spinal Injury Units and Differences in Experts' Recommendations

    Subramanian Vaidyanathan

    2006-01-01

    Full Text Available The objective of this article was to determine the current practice on amikacin dosing and monitoring in spinal cord injury patients from spinal cord physicians and experts. Physicians from spinal units and clinical pharmacologists were asked to provide protocol for dosing and monitoring of amikacin therapy in spinal cord injury patients. In a spinal unit in Poland, amikacin is administered usually 0.5 g twice daily. A once-daily regimen of amikacin is never used and amikacin concentrations are not determined. In Belgium, Southport (U.K., Spain, and the VA McGuire Medical Center (Richmond, Virginia, amikacin is given once daily. Whereas peak and trough concentrations are determined in Belgium, only trough concentration is measured in Southport. In both these spinal units, modification of the dose is not routinely done with a nomogram. In Spain and the VA McGuire Medical Center, monitoring of serum amikacin concentration is not done unless a patient has renal impairment. In contrast, the dose/interval of amikacin is adjusted according to pharmacokinetic parameters at the Edward Hines VA Hospital (Hines, Illinois, where amikacin is administered q24h or q48h, depending on creatinine clearance. Spinal cord physicians from Denmark, Germany, and the Kessler Institute for Rehabilitation (West Orange, New Jersey state that they do not use amikacin in spinal injury patients. An expert from Canada does not recommend determining serum concentrations of amikacin, but emphasizes the value of monitoring ototoxicity and nephrotoxicity. Experts from New Zealand recommend amikacin in conventional twice- or thrice-daily dosing because of the theoretical increased risk of neuromuscular blockade and apnea with larger daily doses in spinal cord injury patients. On the contrary, experts from Greece, Israel, and the U.S. recommend once-daily dosing and determining amikacin pharmacokinetic parameters for each patient. As there is considerable variation in clinical

  18. Pharmacokinetics of Second-Line Antituberculosis Drugs after Multiple Administrations in Healthy Volunteers.

    Park, Sang-In; Oh, Jaeseong; Jang, Kyungho; Yoon, Jangsoo; Moon, Seol Ju; Park, Jong Sun; Lee, Jae Ho; Song, Junghan; Jang, In-Jin; Yu, Kyung-Sang; Chung, Jae-Yong

    2015-08-01

    Therapeutic drug monitoring (TDM) of second-line antituberculosis drugs would allow for optimal individualized dosage adjustments and improve drug safety and therapeutic outcomes. To evaluate the pharmacokinetic (PK) characteristics of clinically relevant, multidrug treatment regimens and to improve the feasibility of TDM, we conducted an open-label, multiple-dosing study with 16 healthy subjects who were divided into two groups. Cycloserine (250 mg), p-aminosalicylic acid (PAS) (5.28 g), and prothionamide (250 mg) twice daily and pyrazinamide (1,500 mg) once daily were administered to both groups. Additionally, levofloxacin (750 mg) and streptomycin (1 g) once daily were administered to group 1 and moxifloxacin (400 mg) and kanamycin (1 g) once daily were administered to group 2. Blood samples for PK analysis were collected up to 24 h following the 5 days of drug administration. The PK parameters, including the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve during a dosing interval at steady state (AUCτ), were evaluated. The correlations between the PK parameters and the concentrations at each time point were analyzed. The mean Cmax and AUCτ, respectively, for each drug were as follows: cycloserine, 24.9 mg/liter and 242.3 mg · h/liter; PAS, 65.9 mg/liter and 326.5 mg · h/liter; prothionamide, 5.3 mg/liter and 22.1 mg · h/liter; levofloxacin, 6.6 mg/liter and 64.4 mg · h/liter; moxifloxacin, 4.7 mg/liter and 54.2 mg · h/liter; streptomycin, 42.0 mg/liter and 196.7 mg · h/liter; kanamycin, 34.5 mg/liter and 153.5 mg · h/liter. The results indicated that sampling at 1, 2.5, and 6 h postdosing is needed for TDM when all seven drugs are administered concomitantly. This study indicates that PK characteristics must be considered when prescribing optimal treatments for patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT02128308.). Copyright © 2015, American Society for

  19. Efficacy and safety of QVA149 compared to the concurrent administration of its monocomponents indacaterol and glycopyrronium: the BEACON study

    Dahl R

    2013-10-01

    Full Text Available Ronald Dahl,1 Dalal Jadayel,2 Vijay KT Alagappan,3 Hungta Chen,3 Donald Banerji31Department of Dermatology, Allergy Centre, Odense University Hospital, Odense, Denmark; 2Novartis Horsham Research Centre, Horsham, UK; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USAIntroduction: The BEACON study evaluated the efficacy and safety of QVA149, a once-daily dual bronchodilator containing a fixed-dose combination of the long-acting β2-agonist (LABA indacaterol and long-acting muscarinic antagonist (LAMA glycopyrronium (NVA237, in development for the treatment of patients with chronic obstructive pulmonary disease (COPD, compared with the free-dose concurrent administration of indacaterol plus glycopyrronium (IND+GLY.Methods: In this multicenter, double-blind, parallel group study, patients with stage II or stage III COPD (Global initiative for chronic Obstructive Lung Disease [GOLD] 2010 were randomized (1:1 to once-daily QVA149 (110 µg indacaterol/50 µg glycopyrronium or concurrent administration of indacaterol (150 µg and glycopyrronium (50 µg via the Breezhaler® device (Novartis AG, Basel, Switzerland for 4 weeks. The primary endpoint was to evaluate the noninferiority of QVA149 as compared with concurrent administration of IND+GLY, for trough forced expiratory volume in 1 second (FEV1 after 4 weeks of treatment. The other assessments included FEV1 area under the curve from 0 to 4 hours (AUC0–4 hours at day 1 and week 4, symptom scores, rescue medication use, safety, and tolerability over the 4-week study period.Results: Of 193 patients randomized, 187 (96.9% completed the study. Trough FEV1 at week 4 for QVA149 and IND+GLY was 1.46 L ± 0.02 and 1.46 L ± 0.18, respectively. The FEV1 AUC0–4 hours at day 1 and week 4 were similar between the two treatment groups. Both treatment groups had a similar reduction in symptom scores and rescue medication use for the 4-week treatment period. Overall, 25.6% of patients in QVA149 group

  20. Effects of Glucagon-Like Peptide-1 Receptor Agonists on Weight Loss in Patients with Type 2 Diabetes: A Systematic Review and Network Meta-Analysis

    Feng Sun

    2015-01-01

    Full Text Available To evaluate the effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1 RAs on weight reduction in patients with Type 2 diabetes mellitus (Type 2 DM, a network meta-analysis was conducted. MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched from 1950 to October 2013. Randomized controlled trials (RCTs involving GLP-1 RAs were included if they provided information on body weight. A total of 51 RCTs were included and 17521 participants were enrolled. The mean duration of 51 RCTs was 31 weeks. Exenatide 10 μg twice daily (EX10BID reduced weight compared with exenatide 5 μg twice daily (EX5BID, liraglutide 0.6 mg once daily (LIR0.6QD, liraglutide—1.2 mg once daily (LIR1.2QD, and placebo treatment, with mean differences of −1.07 kg (95% CI: −2.41, −0.02, −2.38 kg (95% CI: −3.71, −1.06, −1.62 kg (95% CI: −2.79, −0.43, and −1.92 kg (95% CI: −2.61, −1.24, respectively. Reductions of weight treated with liraglutide—1.8 mg once daily (LIR1.8QD reach statistical significance (−1.43 kg (95% CI: −2.73, −0.15 versus LIR1.2QD and (−0.98 kg (95% CI: −1.94, −0.02 versus placebo. Network meta-analysis found that EX10BID, LIR1.8QD, and EX2QW obtained a higher proportion of patients with weight loss than other traditional hypoglycemic agents. Our results suggest GLP-1 RAs are promising candidates for weight control in comparison with traditional hypoglycemic drugs, and EX10BID, LIR1.8QD, and EX2QW rank the top three drugs.

  1. Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial.

    Kim, Dong-Wan; Tiseo, Marcello; Ahn, Myung-Ju; Reckamp, Karen L; Hansen, Karin Holmskov; Kim, Sang-We; Huber, Rudolf M; West, Howard L; Groen, Harry J M; Hochmair, Maximilian J; Leighl, Natasha B; Gettinger, Scott N; Langer, Corey J; Paz-Ares Rodríguez, Luis G; Smit, Egbert F; Kim, Edward S; Reichmann, William; Haluska, Frank G; Kerstein, David; Camidge, D Ross

    2017-08-01

    Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression. We evaluated two regimens of brigatinib, an investigational next-generation ALK inhibitor, in crizotinib-refractory ALK-positive NSCLC. Patients and Methods Patients were stratified by brain metastases and best response to crizotinib. They were randomly assigned (1:1) to oral brigatinib 90 mg once daily (arm A) or 180 mg once daily with a 7-day lead-in at 90 mg (180 mg once daily [with lead-in]; arm B). Investigator-assessed confirmed objective response rate (ORR) was the primary end point. Results Of 222 patients enrolled (arm A: n = 112, 109 treated; arm B: n = 110, 110 treated), 154 (69%) had baseline brain metastases and 164 of 222 (74%) had received prior chemotherapy. With 8.0-month median follow-up, investigator-assessed confirmed ORR was 45% (97.5% CI, 34% to 56%) in arm A and 54% (97.5% CI, 43% to 65%) in arm B. Investigator-assessed median progression-free survival was 9.2 months (95% CI, 7.4 to 15.6) and 12.9 months (95% CI, 11.1 to not reached) in arms A and B, respectively. Independent review committee-assessed intracranial ORR in patients with measurable brain metastases at baseline was 42% (11 of 26 patients) in arm A and 67% (12 of 18 patients) in arm B. Common treatment-emergent adverse events were nausea (arm A/B, 33%/40%), diarrhea (arm A/B, 19%/38%), headache (arm A/B, 28%/27%), and cough (arm A/B, 18%/34%), and were mainly grades 1 to 2. A subset of pulmonary adverse events with early onset (median onset: day 2) occurred in 14 of 219 treated patients (all grades, 6%; grade ≥ 3, 3%); none occurred after escalation to 180 mg in arm B. Seven of 14 patients were successfully retreated with brigatinib. Conclusion Brigatinib yielded substantial whole-body and intracranial responses as well as robust progression-free survival; 180 mg (with lead-in) showed

  2. [Effect of Transcutaneuos Acupoint Electrostimulation on Serum Sex Hormone Levels and Expression of Ovarian Steroid Hormone Metabolic Enzymes in Polycystic Ovary Syndrome Rats].

    Zhou, Jian-yong; Zhang, Xiao-yue; Yu, Mei-ling; Lu, Sheng-feng; Chen, Xia

    2016-02-01

    To observe the effect of transcutaneuos acupoint electrostimulation(TAES) on ovarian serum sex hormone levels and ovarian follicle granular cell aromatase cytochrome P 450 (P 450 arom) protein and follicle theca cell cytochrome P 450 17 α-hydroxylase/c 17-20 lyase cytochrome P 450 (P 450 c 17 α) protein expression in polycystic ovary syndrome (PCOS)rats, so as to explore its mechanisms underlying improvement of PCOS. METHODS Forty SD rats were randomly divided into four groups: normal control, model, medication and TAES (10 rats/group). The PCOS model was established by giving (gavage) the animals with letrozole solution (1.0 mg/kg, once daily for 21 consecutive days). Rats of the medication group were treated with Clomiphene (1 mg/kg) once daily for 7 days, and those of the TAES group were treated with electrical stimulation (2 Hz, 3 mA) of "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) areas for 30 min, once daily for 7 consecutive days. The rats body weight and bilateral ovarian weight were detected, and the ovarian structure and follicular development degree were observed under light microscope after H. E. stain, and the serum testosterone (T), estradiol (E2), luteotrophic hormone (LH) and follicle-stimulating hormone (FSH) contents were detected using radioimmunoassay. The expression of ovarian P 450 arom (for production of estrogen)protein and P 450 c 17 α (for production of androgen) protein was detected by using immunohistochemical stain and Western blot, respectively. The body weight, bilateral ovary weight, serum T and LH contents, and ratio of LH/FSH, and ovarian P 450 c 17 α immunoactivity and protein expression levels in the model group were all significantly increased compared with the normal control group (P ovarian P 450 arom immunoactivity and protein expression were significantly decreased after modeling (P ovarian P 450 c 17 α immunoactivity and protein expression levels, and the decreased ovarian P 450 arom immunoactivity and protein expression

  3. Food interactions with sustained-release theophylline preparations. A review.

    Jonkman, J H

    1989-03-01

    Currently, theophylline is being used predominantly as sustained-release capsules or tablets. In the mid-seventies the first preparations for use with a dosage interval of 12 hours (twice-daily preparations) were introduced. Since 1983, theophylline preparations that can be given with an interval of 24 hours (once-daily preparations) have become available. The release of theophylline from some of these products can be influenced (either increased or decreased) by concomitant intake of food. With some preparations the composition of the meal (especially the fat content) has an influence on the degree of effect. The consequence may be an effect on the rate of absorption or on the amount absorbed, or both simultaneously. This could result in an unexpected shift of the plasma theophylline concentration. Such a shift is therapeutically undesirable, because theophylline has a fairly narrow therapeutic range. A review is given of those food interactions with the sustained-release theophylline preparations, both twice-daily and once-daily products, that are currently on the world market. Special attention is paid to the specific (bio)pharmaceutical characteristics of the different products, and to the influence of the composition and timing of the meals. For each preparation the effect of food on the following pharmacokinetic parameters is discussed: area under the plasma concentration-time curve, peak plasma drug concentration and time to reach this peak. Where possible, the results for both adults and children are discussed. There are indications that children are more susceptible to food-effects than adults. The regulatory aspects are mentioned briefly. Clinically important effects of food have been observed with the following twice-daily products: 'Theo-Dur Sprinkle', 'Theolair SR' (= 'Nuelin SR') and 'Theograd'. Pronounced effects could have an even greater impact with once-daily preparations, as the total daily dose will be given at a single time. A particularly

  4. Analysis of 2-Week Data from Two Randomized, Controlled Trials Conducted in Subjects with Frequent Heartburn Treated with Esomeprazole 20 mg.

    Katz, Philip O; Le Moigne, Anne; Pollack, Charles

    2017-05-01

    These secondary analyses used data from 2 similarly designed studies in subjects experiencing frequent heartburn to evaluate the efficacy of esomeprazole 20 mg once daily for 2 weeks, which reflects the approved over-the-counter dosage and duration. Subjects without endoscopically identified erosive esophagitis who were experiencing heartburn for ≥6 months and ≥4 of 7 days prior to baseline (study 1, N = 368; study 2, N = 349) were randomly assigned to receive double-blind treatment with esomeprazole 40 or 20 mg (administered as esomeprazole magnesium trihydrate 44.5 and 22.3 mg, respectively) or placebo once daily for 4 weeks. Subjects recorded the severity of heartburn in a daily diary, and investigators assessed subjects at each study visit. Two-week assessments were the primary end points of interest in these analyses and included the percentage of subjects with complete heartburn resolution (no episodes during 7 consecutive days), time to sustained complete heartburn resolution (the first of 7 consecutive episode-free days), and heartburn relief (no episodes other than ≤1 mild episode during 7 consecutive days). At week 2, the percentages of subjects who experienced complete heartburn resolution were significantly greater with esomeprazole 40 mg (study 1, 26.1%; study 2, 35.3%) and 20 mg (study 1, 25.2%; study 2, 35.7%) compared with placebo (study 1, 9.0%; study 2, 3.4%) (all, P ≤ 0.001). Beginning on day 1, the percentages of subjects who experienced sustained heartburn resolution was significantly greater in the groups treated with esomeprazole 40 mg (study 1, 19%; study 2, 19%; P heartburn relief were significantly greater with esomeprazole 40 mg (study 1, 35.3%; study 2, 40.5%) and 20 mg (study 1, 34.5%; study 2, 46.4%) compared with placebo (study 1, 16.5%; study 2, 8.6%) (all, P ≤ 0.001). The results of this study demonstrate that once-daily treatment with esomeprazole 20 mg for 2 weeks effectively resolved subjects׳ heartburn compared with

  5. Comparative steady-state pharmacokinetic study of an extended-release formulation of itopride and its immediate-release reference formulation in healthy volunteers

    Yoon S

    2014-01-01

    Full Text Available Seonghae Yoon,1,* Howard Lee,2,* Tae-Eun Kim,1 SeungHwan Lee,1 Dong-Hyun Chee,3 Joo-Youn Cho,1 Kyung-Sang Yu,1 In-Jin Jang1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 2Clinical Trials Center, Seoul National University Hospital, 3AbbVie Ltd., Seoul, Republic of Korea *These authors contributed equally to this work Background: This study was conducted to compare the oral bioavailability of an itopride extended-release (ER formulation with that of the reference immediate-release (IR formulation in the fasting state. The effect of food on the bioavailability of itopride ER was also assessed. Methods: A single-center, open-label, randomized, multiple-dose, three-treatment, three-sequence, crossover study was performed in 24 healthy male subjects, aged 22–48 years, who randomly received one of the following treatments for 4 days in each period: itopride 150 mg ER once daily under fasting or fed conditions, or itopride 50 mg IR three times daily in the fasting state. Steady-state pharmacokinetic parameters of itopride, including peak plasma concentration (Cmax and area under the plasma concentration versus time curve over 24 hours after dosing (AUC0–24h, were determined by noncompartmental analysis. The geometric mean ratio of the pharmacokinetic parameters was derived using an analysis of variance model. Results: A total of 24 healthy Korean subjects participated, 23 of whom completed the study. The geometric mean ratio and its 90% confidence interval of once-daily ER itopride versus IR itopride three times a day for AUC0–24h were contained within the conventional bioequivalence range of 0.80–1.25 (0.94 [0.88–1.01], although Cmax was reached more slowly and was lower for itopride ER than for the IR formulation. Food delayed the time taken to reach Cmax for itopride ER, but AUC0–24h was not affected. There were no serious adverse events and both formulations were

  6. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection.

    Walmsley, Sharon L; Antela, Antonio; Clumeck, Nathan; Duiculescu, Dan; Eberhard, Andrea; Gutiérrez, Felix; Hocqueloux, Laurent; Maggiolo, Franco; Sandkovsky, Uriel; Granier, Catherine; Pappa, Keith; Wynne, Brian; Min, Sherene; Nichols, Garrett

    2013-11-07

    Dolutegravir (S/GSK1349572), a once-daily, unboosted integrase inhibitor, was recently approved in the United States for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in combination with other antiretroviral agents. Dolutegravir, in combination with abacavir-lamivudine, may provide a simplified regimen. We conducted a randomized, double-blind, phase 3 study involving adult participants who had not received previous therapy for HIV-1 infection and who had an HIV-1 RNA level of 1000 copies per milliliter or more. Participants were randomly assigned to dolutegravir at a dose of 50 mg plus abacavir-lamivudine once daily (DTG-ABC-3TC group) or combination therapy with efavirenz-tenofovir disoproxil fumarate (DF)-emtricitabine once daily (EFV-TDF-FTC group). The primary end point was the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter at week 48. Secondary end points included the time to viral suppression, the change from baseline in CD4+ T-cell count, safety, and viral resistance. A total of 833 participants received at least one dose of study drug. At week 48, the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter was significantly higher in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (88% vs. 81%, P=0.003), thus meeting the criterion for superiority. The DTG-ABC-3TC group had a shorter median time to viral suppression than did the EFV-TDF-FTC group (28 vs. 84 days, Pdreams, anxiety, dizziness, and somnolence) were significantly more common in the EFV-TDF-FTC group, whereas insomnia was reported more frequently in the DTG-ABC-3TC group. No participants in the DTG-ABC-3TC group had detectable antiviral resistance; one tenofovir DF-associated mutation and four efavirenz-associated mutations were detected in participants with virologic failure in the EFV-TDF-FTC group. Dolutegravir plus abacavir-lamivudine had a better safety profile and was more effective

  7. A comparison of dose-response characteristics of four NTCP models using outcomes of radiation-induced optic neuropathy and retinopathy

    Moiseenko, Vitali; Song, William Y; Mell, Loren K; Bhandare, Niranjan

    2011-01-01

    Biological models are used to relate the outcome of radiation therapy to dose distribution. As use of biological models in treatment planning expands, uncertainties associated with the use of specific models for predicting outcomes should be understood and quantified. In particular, the question to what extent model predictions are data-driven or dependent on the choice of the model has to be explored. Four dose-response models--logistic, log-logistic, Poisson-based and probit--were tested for their ability and consistency in describing dose-response data for radiation-induced optic neuropathy (RION) and retinopathy (RIRP). Dose to the optic nerves was specified as the minimum dose, D min , received by any segment of the organ to which the damage was diagnosed by ophthalmologic evaluation. For retinopathy, the dose to the retina was specified as the highest isodose covering at least 1/3 of the retinal surface (D 33% ) that geometrically covered the observed retinal damage. Data on both complications were modeled separately for patients treated once daily and twice daily. Model parameters D 50 and γ and corresponding confidence intervals were obtained using maximum-likelihood method. Model parameters were reasonably consistent for RION data for patients treated once daily, D 50 ranging from 94.2 to 104.7 Gy and γ from 0.88 to 1.41. Similar consistency was seen for RIRP data which span a broad range of complication incidence, with D 50 from 72.2 to 75.0 Gy and γ from 1.51 to 2.16 for patients treated twice daily; 72.2-74.0 Gy and 0.84-1.20 for patients treated once daily. However, large variations were observed for RION in patients treated twice daily, D 50 from 96.3 to 125.2 Gy and γ from 0.80 to 1.56. Complication incidence in this dataset in any dose group did not exceed 20%. For the considered data sets, the log-logistic model tends to lead to larger D 50 and lower γ compared to other models for all datasets. Statements regarding normal tissue

  8. Short-course oral co-trimoxazole versus intramuscular benzathine benzylpenicillin for impetigo in a highly endemic region: an open-label, randomised, controlled, non-inferiority trial.

    Bowen, Asha C; Tong, Steven Y C; Andrews, Ross M; O'Meara, Irene M; McDonald, Malcolm I; Chatfield, Mark D; Currie, Bart J; Carapetis, Jonathan R

    2014-12-13

    Impetigo affects more than 110 million children worldwide at any one time. The major burden of disease is in developing and tropical settings where topical antibiotics are impractical and lead to rapid emergence of antimicrobial resistance. Few trials of systemic antibiotics are available to guide management of extensive impetigo. As such, we aimed to compare short-course oral co-trimoxazole with standard treatment with intramuscular benzathine benzylpenicillin in children with impetigo in a highly endemic setting. In this randomised, controlled, non-inferiority trial, Indigenous Australian children aged 3 months to 13 years with purulent or crusted non-bullous impetigo were randomly assigned (1:1:1) to receive benzathine benzylpenicillin (weight-banded injection), twice-daily co-trimoxazole for 3 days (4 mg/kg plus 20 mg/kg per dose), or once-daily co-trimoxazole for 5 days (8 mg/kg plus 40 mg/kg per dose). At every visit, participants were randomised in blocks of six and 12, stratified by disease severity. Randomisation was done by research nurses and codes were in sealed, sequentially numbered, opaque envelopes. Independent reviewers masked to treatment allocation compared digital images of sores from days 0 and 7. The primary outcome was treatment success at day 7 in a modified intention-to-treat analysis. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12609000858291. Between Nov 26, 2009, and Nov 20, 2012, 508 patients were randomly assigned to receive benzathine benzylpenicillin (n=165 [156 analysed]), twice-daily co-trimoxazole for 3 days (n=175 [173 analysed]), or once-daily co-trimoxazole for 5 days (n=168 [161 analysed]). Treatment was successful in 133 (85%) children who received benzathine benzylpenicillin and 283 (85%) who received pooled co-trimoxazole (absolute difference 0·5%; 95% CI -6·2 to 7·3), showing non-inferiority of co-trimoxazole (10% margin). Results for twice-daily co-trimoxazole for 3

  9. Evaluating the role of atazanavir/cobicistat and darunavir/cobicistat fixed-dose combinations for the treatment of HIV-1 infection

    Crutchley RD

    2016-03-01

    Full Text Available Rustin D Crutchley,1 Rakesh C Guduru,2 Amy M Cheng1 1Department of Pharmacy Practice and Translational Research, College of Pharmacy, University of Houston, 2CompanionDX, Houston, TX, USA Abstract: Atazanavir/cobicistat (ATV/c and darunavir/cobicistat (DRV/c are newly approved once daily fixed-dose protease inhibitor combinations for the treatment of HIV-1 infection. Studies in healthy volunteers have established bioequivalence between cobicistat and ritonavir as pharmacoenhancers of both atazanavir (ATV and darunavir (DRV. In addition, two randomized clinical trials (one Phase II and one Phase III noninferiority trial with a 144-week follow-up period demonstrated that cobicistat had sustainable and comparable efficacy and safety to ritonavir as a pharmacoenhancer of ATV through 144 weeks of treatment in HIV-1-infected patients. Furthermore, one Phase III, open-label, single-arm, clinical trial reflected virologic and immunologic responses and safety outcomes consistent with prior published data for DRV/ritonavir 800/100 mg once daily, supporting the use of DRV/c 800/150 mg once daily for future treatment of treatment-naïve and -experienced HIV-1-infected patients with no DRV resistance-associated mutations. Low rates of virologic failure secondary to resistance to antiretroviral regimens were present in these clinical studies. Most notable adverse events in the ATV studies were hyperbilirubinemia and in the DRV study rash. Small increases in serum creatinine and minimally reduced estimated glomerular filtration rate Cockcroft–Gault calculation (eGFRCG were observed in ATV/c and DRV/c clinical studies consistent with other studies evaluating elvitegravir/cobicistat/tenofovir/emtricitabine for the treatment of HIV-1 infection. These renal parameter changes occurred acutely in the first few weeks and plateaued off for the remaining study periods and are not necessarily clinically relevant. Cobicistat has numerous advantages compared to

  10. Pharmacokinetics of terbinafine in little brown myotis (Myotis lucifugus) infected with Pseudogymnoascus destructans.

    Court, Michael H; Robbins, Alison H; Whitford, Anne M; Beck, Erika V; Tseng, Flo S; Reeder, DeeAnn M

    2017-01-01

    OBJECTIVE To determine the pharmacokinetics of terbinafine in little brown myotis (Myotis lucifugus) infected with Pseudogymnoascus destructans. ANIMALS 123 bats from a P destructans-infected hibernation site in Virginia. PROCEDURES 3 bats were euthanized and necropsied to confirm the presence of P destructans within the population. The remaining 120 bats were systematically assigned to 6 groups (20 bats/group). Bats in each of 3 groups received 6, 20, or 60 mg of terbinafine/kg, SC, once daily for 10 days. Bats in another group received 200 mg of terbinafine/kg, SC, once daily for 5 days. Bats in 1 group received the terbinafine vehicle solution (0.1 mL/kg, SC, once daily for 10 days). Bats in the remaining group did not receive any treatment. Following the treatment period (days 1 through 10), bats were housed in a hibernation chamber and monitored daily until euthanasia on day 42, 75, or 109. Tissue specimens were collected from all bats as soon as possible after death or euthanasia to determine terbinafine concentration. Within each group and tissue type, terbinafine concentration data were pooled, and pharmacokinetic parameters were calculated by noncompartmental methods. RESULTS Adverse neurologic effects and a high mortality rate before day 10 were observed in bats that received the highest terbinafine dose (200 mg/kg) but not those that received lower doses. Presumed therapeutic terbinafine concentrations (≥ 2 μg/g) were maintained in skin and wing for at least 30 and 6 days in bats that received the 60 and 20 mg/kg doses, respectively, but were not achieved in most bats that received the 6 mg/kg dose. Tissue terminal half-life ranged from 14 to 22 days. Terbinafine concentration in hair was positively correlated with that in skin and wing. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated terbinafine doses > 6 but destructans-infected bats. Collection of serial hair specimens may represent a noninvasive method for monitoring terbinafine concentration

  11. A Phase III, Multicenter, Parallel-Design Clinical Trial to Compare the Efficacy and Safety of 5% Minoxidil Foam Versus Vehicle in Women With Female Pattern Hair Loss.

    Bergfeld, Wilma; Washenik, Ken; Callender, Valerie; Zhang, Paul; Quiza, Carlos; Doshi, Uday; Blume-Peytavi, Ulrike

    2016-07-01

    BACKGROUND Female pattern hair loss (FPHL) is a common hair disorder that affects millions of women. A new 5% minoxidil topical foam (MTF) formulation, which does not contain propylene glycol, has been developed. To compare the efficacy and safety of once-daily 5% MTF with vehicle foam for the treatment of FPHL. This was a Phase III, randomized, double-blind, vehicle-controlled, parallel-group, international multicenter trial (17 sites) in women aged at least 18 years with FPHL (grade D3 to D6 on the Savin Density Scale), treated once daily with 5% MTF or vehicle foam for 24 weeks. The co-primary efficacy endpoints were the change from baseline at week 24 in target area hair count (TAHC) and subject assessment of scalp coverage. Also evaluated were TAHC at week 12, expert panel review of hair regrowth at week 24, and change from baseline in total unit area density (TUAD, sum of hair diameters/cm2) at weeks 12 and 24. A total of 404 women were enrolled. At 12 and 24 weeks, 5% MTF treatment resulted in regrowth of 10.9 hairs/cm2 and 9.1 hairs/cm2 more than vehicle foam, respectively (both P<.0001). Improved scalp coverage at week 24 was observed by both subject self-assessment (0.69-point improvement over vehicle foam; P<.0001) and expert panel review (0.36-point improvement over the vehicle foam; P<.0001). TUAD increased by 658 μm/cm2 and 644 μm/cm2 more with 5% MTF than with vehicle foam at weeks 12 and 24, respectively (both P<.0001). MTF was well tolerated. A low incidence of scalp irritation and facial hypertrichosis was observed, with no clinically significant differences between groups. Five percent MTF once daily for 24 weeks was well tolerated and promoted hair regrowth in women with FPHL, resulting in improved scalp coverage and increased hair density compared with vehicle foam. ClinicalTrials.gov identifier: nCT01226459J Drugs Dermatol. 2016;15(7):874-881.

  12. Treatment of chronic telogen effluvium with oral minoxidil: A retrospective study [version 1; referees: 2 approved

    Eshini Perera

    2017-09-01

    Full Text Available Background: Chronic telogen effluvium (CTE may be primary or secondary to various causes, including drug reaction, nutritional deficiency and female pattern hair loss (FPHL.  Oral minoxidil stimulates hair growth, and topical minoxidil is used in the treatment of FPHL and male androgenetic alopecia. minoxidil has not been used to treat CTE. This study aimed to assess the treatment of CTE with once daily oral minoxidil. Methods: Women with a diagnosis of CTE based on >6 month history of increased telogen hair shedding, no visible mid frontal scalp hair loss (Sinclair stage 1 and no hair follicle miniaturization on scalp biopsy were treated with once daily oral minoxidil.  Hair shedding scores (HSS at baseline, 6 and 12 months were analysed using the Wilcoxon rank sum test for pair-wise comparisons. Results: Thirty-six women were treated with oral minoxidil (range, 0.25-2.5 mg daily for 6 months.  Mean age was 46.9 years (range 20-83, HSS at baseline was 5.64, and duration of diagnosis was 6.55 years (range 1-27.  There was a reduction in mean HSS scores from baseline to 6 months of 1.7 (p<0.001 and baseline to 12 months of 2.58 (p<0.001. Five women who described trichodynia at baseline, noted improvement or resolution within 3 months.  Mean change in blood pressure was minus 0.5 mmHg systolic and plus 2.1 mmHg diastolic.  Two patients developed transient postural dizziness that resolved with continued treatment.  One patient developed ankle oedema.  Thirteen women developed facial hypertrichosis.  For 6 patients this was mild and did not require treatment; 4 had waxing of their upper lip or forehead; 3 had laser hair removal.  No patients developed any haematological abnormality.  All 36 women completed 12 months of treatment. Conclusions: Once daily oral minoxidil appears to reduce hair shedding in CTE.  Placebo controlled studies are recommended to further assess this response.

  13. Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial.

    Cortes, Jorge E; Saglio, Giuseppe; Kantarjian, Hagop M; Baccarani, Michele; Mayer, Jiří; Boqué, Concepción; Shah, Neil P; Chuah, Charles; Casanova, Luis; Bradley-Garelik, Brigid; Manos, George; Hochhaus, Andreas

    2016-07-10

    We report the 5-year analysis from the phase III Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients (DASISION) trial, evaluating long-term efficacy and safety outcomes of patients with chronic myeloid leukemia (CML) in chronic phase (CP) treated with dasatinib or imatinib. Patients with newly diagnosed CML-CP were randomly assigned to receive dasatinib 100 mg once daily (n = 259) or imatinib 400 mg once daily (n = 260). At the time of study closure, 61% and 63% of dasatinib- and imatinib-treated patients remained on initial therapy, respectively. Cumulative rates of major molecular response and molecular responses with a 4.0- or 4.5-log reduction in BCR-ABL1 transcripts from baseline by 5 years remained statistically significantly higher for dasatinib compared with imatinib. Rates for progression-free and overall survival at 5 years remained high and similar across treatment arms. In patients who achieved BCR-ABL1 ≤ 10% at 3 months (dasatinib, 84%; imatinib, 64%), improvements in progression-free and overall survival and lower rates of transformation to accelerated/blast phase were reported compared with patients with BCR-ABL1 greater than 10% at 3 months. Transformation to accelerated/blast phase occurred in 5% and 7% of patients in the dasatinib and imatinib arms, respectively. Fifteen dasatinib-treated and 19 imatinib-treated patients had BCR-ABL1 mutations identified at discontinuation. There were no new or unexpected adverse events identified in either treatment arm, and pleural effusion was the only drug-related, nonhematologic adverse event reported more frequently with dasatinib (28% v 0.8% with imatinib). First occurrences of pleural effusion were reported with dasatinib, with the highest incidence in year 1. Arterial ischemic events were uncommon in both treatment arms. These final results from the DASISION trial continue to support dasatinib 100 mg once daily as a safe and effective first-line therapy for the long

  14. A randomized, double-blind, multicenter Phase II study comparing the efficacy and safety of oral nemonoxacin with oral levofloxacin in the treatment of community-acquired pneumonia.

    Liu, Yang; Zhang, Yingyuan; Wu, Jufang; Zhu, Demei; Sun, Shenghua; Zhao, Li; Wang, Xuefeng; Liu, Hua; Ren, Zhenyi; Wang, Changzheng; Xiu, Qingyu; Xiao, Zuke; Cao, Zhaolong; Cui, Shehuai; Yang, Heping; Liang, Yongjie; Chen, Ping; Lv, Yuan; Hu, Chengping; Lv, Xiaoju; Liu, Shuang; Kuang, Jiulong; Li, Jianguo; Wang, Dexi; Chang, Liwen

    2017-12-01

    To compare the clinical efficacy and safety of nemonoxacin with levofloxacin in treating community-acquired pneumonia (CAP) in a Phase II clinical trial. One hundred ninety-two patients with CAP were randomized to receive oral nemonoxacin (500 mg or 750 mg) or levofloxacin (500 mg) once daily for 7-10 days. Clinical and bacteriological responses were determined at the test of cure (TOC) visit in the full analysis set (FAS). The clinical cure rate of nemonoxacin (500 mg), nemonoxacin (750 mg), and levofloxacin (500 mg) was 93.3%, 87.3%, and 88.5%, respectively, in the FAS (n = 168), and 93.0%, 93.9%, and 88.9%, respectively in the per protocol set (n = 152). At the TOC visit, nemonoxacin at 500 mg and 750 mg was proven to be noninferior to levofloxacin at 500 mg in the FAS in terms of clinical efficacy. The overall bacteriological success rate was 83.3% in both nemonoxacin groups and 80.0% in the levofloxacin 500 mg group in the bacteriological FAS. The comprehensive efficacy rate was comparable among the three groups (87.5% for the nemonoxacin 500 mg group, 93.8% for the nemonoxacin 750 mg group, and 81.3% for the levofloxacin 500 mg group). Most drug-related adverse events were mild and transient, mainly gastrointestinal symptoms such as nausea and vomiting, transient neutropenia, and elevated liver enzymes. No drug-related serious adverse events occurred. Either 500 mg or 750 mg of oral nemonoxacin taken once daily for 7-10 days demonstrated high clinical and bacteriological success rates in Chinese adult patients with CAP. Nemonoxacin at 500 mg once daily for 7-10 days is recommended for future Phase III clinical trials. ClinicalTrials.gov identifier: NCT01537250. Copyright © 2015. Published by Elsevier B.V.

  15. Generation of Maillard compounds from inulin during the thermal processing of Agave tequilana Weber Var. azul.

    Mancilla-Margalli, Norma A; López, Mercedes G

    2002-02-13

    During the cooking process of Agave tequilana Weber var. azul to produce tequila, besides the hydrolysis of inulin to generate fermentable sugars, many volatiles, mainly Maillard compounds, are produced, most of which may have a significant impact on the overall flavor of tequila. Exudates (agave juice) from a tequila company were collected periodically, and color, Brix, fructose concentration, and reducing sugars were determined as inulin breakdown took place. Maillard compounds were obtained by extraction with CH(2)Cl(2), and the extracts were analyzed by GC-MS. Increments in color, Brix, and reducing sugars were observed as a function of time, but a decrease in fructose concentration was found. Many Maillard compounds were identified in the exudates, including furans, pyrans, aldehydes, and nitrogen and sulfur compounds. The most abundant Maillard compounds were methyl-2-furoate, 2,3-dihydroxy-3,5-dihydro-6-methyl-4(H)-pyran-4-one, and 5-(hydroxymethyl)furfural. In addition, a series of short- and long-chain fatty acids was also found. A large number of the volatiles in A. tequilana Weber var. azul were also detected in tequila extracts, and most of these have been reported as a powerful odorants, responsible for the unique tequila flavor.

  16. PYROLIGNEOUS LIQUOR PRODUCED FROM ACACIA MEARNSII DE WILD WOOD UNDER CONTROLLED CONDITIONS AS A RENEWABLE SOURCE OF CHEMICALS

    Carolina M. Furtado

    2015-09-01

    Full Text Available Acacia mearnsii de Wild (black wattle is one of the most important trees planted in Southern Brazil for tannin extraction and charcoal production. The pyrolysis of the black wattle wood used for obtaining charcoal is performed in brick ovens, with the gas fraction being sent directly into the environment. The present study examines the condensable compounds present in the liquor produced from black wattle wood at different thermal degradation conditions, using gas chromatography coupled with mass spectrometry (GC/MS. Branches of black wattle were thermally degraded at controlled ambient and temperature conditions. Overall, a higher variety of compounds were obtained under atmospheric air pressure than under synthetic air pressure. Most of the tentatively identified compounds, such as carboxylic acids, phenols, aldehydes, and low molecular mass lignin fragments, such as guayacol, syringol, and eugenol, were products of lignin thermoconversion. Substituted aromatic compounds, such as vanillin, ethyl vanillin, and 2-methoxy-4-propeny-phenol, were also identified. At temperatures above 200 ºC, furan, 2-acetylfuran, methyl-2-furoate, and furfural, amongst others, were identified as polysaccharide derivatives from cellulose and hemicellulose depolymerization. This study evidences the need for adequate management of the condensable by-products of charcoal production, both for economic reasons and for controlling their potential environmental impact.

  17. Simultaneous determination of some antiprotozoal drugs in different combined dosage forms by mean centering of ratio spectra and multivariate calibration with model updating methods

    Abdelaleem Eglal A

    2012-04-01

    Full Text Available Abstract Background Metronidazole (MET and Diloxanide Furoate (DF, act as antiprotozoal drugs, in their ternary mixtures with Mebeverine HCl (MEH, an effective antispasmodic drug. This work concerns with the development and validation of two simple, specific and cost effective methods mainly for simultaneous determination of the proposed ternary mixture. In addition, the developed multivariate calibration model has been updated to determine Metronidazole benzoate (METB in its binary mixture with DF in Dimetrol® suspension. Results Method (I is the mean centering of ratio spectra spectrophotometric method (MCR that depends on using the mean centered ratio spectra in two successive steps that eliminates the derivative steps and therefore the signal to noise ratio is enhanced. The developed MCR method has been successfully applied for determination of MET, DF and MEH in different laboratory prepared mixtures and in tablets. Method (II is the partial least square (PLS multivariate calibration method that has been optimized for determination of MET, DF and MEH in Dimetrol ® tablets and by updating the developed model, it has been successfully used for prediction of binary mixtures of DF and Metronidazole Benzoate ester (METB in Dimetrol ® suspension with good accuracy and precision without reconstruction of the calibration set. Conclusion The developed methods have been validated; accuracy, precision and specificity were found to be within the acceptable limits. Moreover results obtained by the suggested methods showed no significant difference when compared with those obtained by reported methods. Graphical Abstract

  18. Antigenotoxic potential of Asparagus racemosus root extract against electron beam radiation induced micronuclei formation in Swiss albino mice

    Bhandary, B. Satheesh Kumar; Sharmila, K.P.; Suchetha Kumari, N.; Bhat, Vadish S.; Shetty, Jayaram; Peter, Alex John; Jose, Jerish M.; Fernandes, Ronald

    2016-01-01

    To evaluate the antigenotoxic potential of Asparagus Racemosus Root ethanolic extract (ARE) against electron beam radiation induced micronuclei formation in Swiss albino mice. Micronucleus assay was performed in the bone marrow of Swiss albino mice according to the method of Hosseinimehr et al., 2003. The experimental animals were orally administered 200 mg/kg body weight of ARE once daily for 15 consecutive days. At the end of experimental period, the animals were euthanized and the bone marrow was collected from the femur. Control (C), Radiation control (RC) and drug control (DC) group was also maintained. The number of radiation induced Micronucleated Polychromatic Erythrocytes (MnPCE) and Micronucleated Normochromatic Erythrocytes were decreased in the ARE treated mice which was statistically significant (p<0.05) compared to radiation control group. Present findings demonstrate the antigenotoxic potential of ARE against electron beam radiation induced micronuclei formation which may be attributed to scavenging of radiation-induced free radicals

  19. Ameliorative Activity of Ethanolic Extract of Artocarpus heterophyllus Stem Bark on Alloxan-induced Diabetic Rats

    Basiru Olaitan Ajiboye

    2018-03-01

    Full Text Available Purpose: Diabetes mellitus is one of the major endocrine disorders, characterized by impaired insulin action and deficiency. Traditionally, Artocarpus heterophyllus stem bark has been reputably used in the management of diabetes mellitus and its complications. The present study evaluates the ameliorative activity of ethanol extract of Artocarpus heterophyllus stem bark in alloxan-induced diabetic rats. Methods: Diabetes mellitus was induced by single intraperitoneal injection of 150 mg/kg body weight of alloxan and the animals were orally administered with 50, 100 and 150 mg/kg body weight ethanol extract of Artocarpus heterophyllus stem bark once daily for 21 days. Results: At the end of the intervention, diabetic control rats showed significant (p0.05 different with non-diabetic rats. Conclusion: The results suggest that ethanol extract of Artocarpus heterophyllus stem bark may be useful in ameliorating complications associated with diabetes mellitus patients.

  20. Optimal dose of losartan for renoprotection in diabetic nephropathy

    Andersen, Steen; Rossing, Peter; Juhl, Tina R

    2002-01-01

    filtration rate (GFR) ([(51)Cr]EDTA plasma clearance) were determined. RESULTS: Baseline values of albuminuria (geometric mean (95% CI)) and GFR (means+/-SEM) were 1138 (904-1432) mg/24 h and 91+/-3 ml/min/1.73 m(2), respectively. The blood pressure at baseline was 155/81+/-3/2 mmHg. All doses of losartan...... consecutive hypertensive type 1 diabetic patients with diabetic nephropathy received increasing doses of losartan, 50, 100, and 150 mg once daily in three periods each lasting 2 months. At baseline and at the end of each treatment period, albuminuria, 24-h blood pressure (TM2420 A&D), and glomerular...

  1. Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)

    Jorsal, Anders; Kistorp, Caroline Micheala Nervil; Holmager, Pernille

    2017-01-01

    trial. Patients (n = 241) with reduced left ventricular ejection fraction (LVEF ≤45%) were recruited (February 2012 to August 2015). Patients were clinically stable and on optimal heart failure treatment. Intervention was liraglutide 1.8 mg once daily or matching placebo for 24 weeks. The LVEF...... with and without diabetes. Treatment with liraglutide was associated with an increase in heart rate and more serious cardiac adverse events, and this raises some concern with respect to the use of liraglutide in patients with chronic heart failure and reduced left ventricular function. More data on the safety......AIMS: To determine the effect of the glucagon-like peptide-1 analogue liraglutide on left ventricular function in chronic heart failure patients with and without type 2 diabetes. METHODS AND RESULTS: LIVE was an investigator-initiated, randomised, double-blinded, placebo-controlled multicentre...

  2. Tubular and glomerular injury in diabetes and the impact of ACE inhibition

    Nielsen, Stine E; Sugaya, Takeshi; Tarnow, Lise

    2009-01-01

    OBJECTIVE: We studied tubular and glomerular damage in type 1 diabetic patients by measuring urinary-liver fatty acid binding protein (U-LFABP) and albuminuria. Subsequently, we evaluated the effect of ACE inhibition on U-LFABP in patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS: We...... studied Caucasians with type 1 diabetes: 58 with normoalbuminuria (urinary albumin or =300 mg/24 h). A control group consisted of 57 healthy individuals. The groups were matched by sex...... and duration of diabetes. In addition, U-LFABP was measured in 48 type 1 diabetic patients with diabetic nephropathy in a randomized crossover trial consisting of 2 months of treatment with 20, 40, and 60 mg lisinopril once daily in random order. RESULTS: In the cross-sectional study, levels of U-LFABP were...

  3. Zingiber officinale Improves Cognitive Function of the Middle-Aged Healthy Women

    Naritsara Saenghong

    2012-01-01

    Full Text Available The development of cognitive enhancers from plants possessing antioxidants has gained much attention due to the role of oxidative stress-induced cognitive impairment. Thus, this study aimed to determine the effect of ginger extract, or Zingiber officinale, on the cognitive function of middle-aged, healthy women. Sixty participants were randomly assigned to receive a placebo or standardized plant extract at doses of 400 and 800 mg once daily for 2 months. They were evaluated for working memory and cognitive function using computerized battery tests and the auditory oddball paradigm of event-related potentials at three different time periods: before receiving the intervention, one month, and two months. We found that the ginger-treated groups had significantly decreased P300 latencies, increased N100 and P300 amplitudes, and exhibited enhanced working memory. Therefore, ginger is a potential cognitive enhancer for middle-aged women.

  4. Zingiber officinale Improves Cognitive Function of the Middle-Aged Healthy Women

    Saenghong, Naritsara; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Tongun, Terdthai; Piyavhatkul, Nawanant; Banchonglikitkul, Chuleratana; Kajsongkram, Tanwarat

    2012-01-01

    The development of cognitive enhancers from plants possessing antioxidants has gained much attention due to the role of oxidative stress-induced cognitive impairment. Thus, this study aimed to determine the effect of ginger extract, or Zingiber officinale, on the cognitive function of middle-aged, healthy women. Sixty participants were randomly assigned to receive a placebo or standardized plant extract at doses of 400 and 800 mg once daily for 2 months. They were evaluated for working memory and cognitive function using computerized battery tests and the auditory oddball paradigm of event-related potentials at three different time periods: before receiving the intervention, one month, and two months. We found that the ginger-treated groups had significantly decreased P300 latencies, increased N100 and P300 amplitudes, and exhibited enhanced working memory. Therefore, ginger is a potential cognitive enhancer for middle-aged women. PMID:22235230

  5. Aspects of physiological effects of sodium zeolite A supplementation in dry, non-pregnant dairy cows fed grass silage

    Enemark, J M; Frandsen, A M; Thilsing-Hansen, T

    2003-01-01

    The objective of the present study was to monitor serum and urine biochemical changes in dairy cows during and after oral administration of a synthetic sodium aluminium-silicate (zeolite A). A prospective longitudinal study involving four non-pregnant and non-lactating cows was chosen. Cows were......), while cows in the experimental group were fed the basic diet and supplemented with 1 kg zeolite pellets once daily. During the third week (period 3) both groups were fed the basic ration only and observed for any persistent effects after zeolite withdraw. Daily sampling included blood and urine....... Selected physiological parameters were compared between groups during period 2 and 3, whereas mean values from period 1, 2 and 3 were compared within the groups. Zeolite supplementation revealed a significant influence on calcium homeostasis. A slight decrease in serum Ca and in renal excretion of calcium...

  6. Penile vibratory stimulation in the recovery of urinary continence and erectile function after nerve-sparing radical prostatectomy

    Fode, Mikkel; Borre, Michael; Ohl, Dana A

    2014-01-01

    OBJECTIVE: To examine the effect of penile vibratory stimulation (PVS) in the preservation and restoration of erectile function and urinary continence in conjunction with nerve-sparing radical prostatectomy (RP). PATIENTS AND METHODS: The present study was conducted between July 2010 and March 2013...... were instructed in using a PVS device (FERTI CARE(®) vibrator). Stimulation was performed at the frenulum once daily by the patients in their own homes for at least 1 week before surgery. After catheter removal, daily PVS was re-initiated for a period of 6 weeks. Participants were evaluated at 3, 6...... for analyses (30 patients randomized to PVS and 38 patients randomized to the control group). The IIEF-5 score was highest in the PVS group at all time points after surgery with a median score of 18 vs 7.5 in the control group at 12 months (P = 0.09), but the difference only reached borderline significance...

  7. Comparison Review of Short-Acting and Long-Acting Glucagon-like Peptide-1 Receptor Agonists.

    Uccellatore, Annachiara; Genovese, Stefano; Dicembrini, Ilaria; Mannucci, Edoardo; Ceriello, Antonio

    2015-09-01

    Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) are useful tools for treating type 2 diabetes mellitus. In their recent position statement, the American Diabetes Association and European Association for the Study of Diabetes recommend GLP1-RAs as add-on to metformin when therapeutic goals are not achieved with monotherapy, particularly for patients who wish to avoid weight gain or hypoglycemia. GLP1-RAs differ substantially in their duration of action, frequency of administration and clinical profile. Members of this class approved for clinical use include exenatide twice-daily, exenatide once-weekly, liraglutide and lixisenatide once-daily. Recently, two new once-weekly GLP1-RAs have been approved: dulaglutide and albiglutide. This article summarizes properties of short- and long-acting GLP-1 analogs, and provides useful information to help choose the most appropriate compound for individual patients.

  8. [ACE inhibitors and the kidney].

    Hörl, W H

    1996-01-01

    Treatment with ACE inhibitors results in kidney protection due to reduction of systemic blood pressure, intraglomerular pressure, an antiproliferative effect, reduction of proteinuria and a lipid-lowering effect in proteinuric patients (secondary due to reduction of protein excretion). Elderly patients with diabetes melitus, coronary heart disease or peripheral vascular occlusion are at risk for deterioration of kidney function due to a high frequency of renal artery stenosis in these patients. In patients with renal insufficiency dose reduction of ACE inhibitors is necessary (exception: fosinopril) but more important is the risk for development of hyperkalemia. Patients at risk for renal artery stenosis and patients pretreated with diuretics should receive a low ACE inhibitor dosage initially ("start low - go slow"). For compliance reasons once daily ACE inhibitor dosage is recommended.

  9. Low-dose budesonide treatment improves lung function in patients with infrequent asthma symptoms at baseline

    Reddel, H. K.; Busse, W. W.; Pedersen, Søren

    2015-01-01

    symptom frequency groups (Figure). CONCLUSIONS: Long-term, once-daily, low-dose budesonide treatment plus usual asthma medication improves lung function in patients with mild, recent-onset asthma. These beneficial effects were seen even in patients with the lowest baseline asthma symptom frequency (0......RATIONALE: Inhaled corticosteroids (ICS) are highly effective in low doses for improving asthma outcomes, including lung function. In the past, ICS treatment was recommended for patients with 'persistent' asthma, defined by symptoms >2 days/week.1 However, evidence is lacking for the benefit of ICS...... in patients with less frequent symptoms at presentation. This was investigated in a post-hoc analysis of the multinational inhaled Steroid Treatment As Regular Therapy in early asthma (START) study.2 METHODS: Patients aged 4-66 years (median 21 years) with a history of recent-onset mild asthma (11 years...

  10. Systemic immunogenicity of para-Phenylenediamine and Diphenylcyclopropenone

    Svalgaard, Jesper Dyrendom; Særmark, Carina; Dall, Morten

    2014-01-01

    p-Phenylenediamine (PPD) and Diphenylcyclopropenone (DPCP) are two potent haptens. Both haptens are known to cause delayed-type hypersensitivity, involving a cytokine response and local infiltration of T-cell subpopulations, resulting in contact dermatitis. We investigated the systemic immune...... effects of PPD and DPCP, two relatively unexplored skin allergens. The dorsal sides of the ears of BALB/c mice were exposed to PPD or DPCP (0.1% w/v or 0.01% w/v), or vehicle alone. Mice were treated once daily for 3 days (induction period) and subsequently twice per week for 8 weeks. Local and systemic...... immune responses in the auricular and pancreatic lymph nodes, spleen, liver, serum, and ears were analyzed with cytokine profiling MSD, flow cytometry, and qPCR. Ear swelling increased significantly in mice treated with 1% PPD, 0.01% DPCP or 0.1% DPCP, compared with vehicle treatment, indicating...

  11. Efficacy of 1.25% amitraz solution in the treatment of generalized demodicosis (eight cases) and sarcoptic mange (five cases) in dogs.

    Hugnet, C; Bruchon-Hugnet, C; Royer, H; Bourdoiseau, G

    2001-04-01

    Eight dogs with generalized demodicosis and five with sarcoptic manage were treated with 1.25% amitraz solution applied weekly and associated with an antidote treatment (atipamezol, 0.1 mg kg-1 i.m. once: and yohimbine 0.1 mg kg-1 once daily for 3 days, orally). Results of skin scrapings were used to determine whether therapy should be continued or stopped. The median number of treatments for demodicosis and sarcoptic mange was three (range 2-5) and two (range 1-3), respectively. Some side-effects were observed but all were stopped with antidote treatment; no failure or relapses occurred at 6-36 months after treatment.

  12. Vitamin D and Risk for Vitamin A Intoxication in an 18-Month-Old Boy

    Valentina Talarico

    2016-01-01

    Full Text Available An 18-month-old boy presented with abdominal pain, vomiting, diarrhea, and poor appetite for 6 days. He had been given a multivitamin preparation once daily, containing 50.000 IU of vitamin D and 10.000 IU of vitamin A for a wide anterior fontanelle for about three months. He presented with hypercalcemia, low levels of parathyroid hormone (PTH, and very high serum 25-hydroxyvitamin D (25-OHD levels. Renal ultrasound showed nephrocalcinosis. He did not have sign or symptom of vitamin A intoxication. Patient was successfully treated with intravenous hydration, furosemide, and prednisolone. With treatment, serum calcium returned rapidly to the normal range and serum 25-OHD levels were reduced progressively. In conclusion the diagnosis of vitamin D deficiency rickets without checking 25-OHD levels may cause redundant treatment that leads to vitamin D intoxication (VDI.

  13. Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations

    Farooqui, Mohammed Z H; Valdez, Janet; Martyr, Sabrina

    2015-01-01

    BACKGROUND: Patients with chronic lymphocytic leukaemia (CLL) with TP53 aberrations respond poorly to first-line chemoimmunotherapy, resulting in early relapse and short survival. We investigated the safety and activity of ibrutinib in previously untreated and relapsed or refractory CLL with TP53...... aberrations. METHODS: In this investigator-initiated, single-arm phase 2 study, we enrolled eligible adult patients with active CLL with TP53 aberrations at the National Institutes of Health Clinical Center (Bethesda, MD, USA). Patients received 28-day cycles of ibrutinib 420 mg orally once daily until...... in one (2%) patient. INTERPRETATION: The activity and safety profile of single-agent ibrutinib in CLL with TP53 aberrations is encouraging and supports its consideration as a novel treatment option for patients with this high-risk disease in both first-line and second-line settings. FUNDING: Intramural...

  14. Pharmacokinetics of prolonged-release tacrolimus and implications for use in solid organ transplant recipients.

    Tanzi, Maria G; Undre, Nasrullah; Keirns, James; Fitzsimmons, William E; Brown, Malcolm; First, M Roy

    2016-08-01

    Prolonged-release tacrolimus was developed as a once-daily formulation with ethylcellulose as the excipient, resulting in slower release and reduction in peak concentration (Cmax ) for a given dose compared with immediate-release tacrolimus, which is administered twice daily. This manuscript reviews pharmacokinetic information on prolonged-release tacrolimus in healthy subjects, in transplant recipients converted from immediate-release tacrolimus, and in de novo kidney and liver transplant recipients. As with the immediate-release formulation, prolonged-release tacrolimus shows a strong correlation between trough concentration (Cmin ) and area under the 24-hour time-concentration curve (AUC24 ), indicating that trough whole blood concentrations provide an accurate measure of drug exposure. We present the pharmacokinetic similarities and differences between the two formulations, so that prescribing physicians will have a better understanding of therapeutic drug monitoring in patients receiving prolonged-release tacrolimus. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans.

    List, James F; Whaley, Jean M

    2011-03-01

    Glucose is freely filtered in the glomeruli before being almost entirely reabsorbed into circulation from the proximal renal tubules. The sodium-glucose cotransporter 2 (SGLT2), present in the S1 segment of the proximal tubule, is responsible for the majority of glucose reabsorption. SGLT2 inhibitors reduce glucose reabsorption and increase urinary glucose excretion. In animal models and humans with type 2 diabetes, this effect is associated with reduced fasting and postprandial blood glucose levels, and reduced hemoglobin A1c. Animal studies suggest that reduction of hyperglycemia with SGLT2 inhibitors may also improve insulin sensitivity and preserve β-cell function. Urinary excretion of excess calories with SGLT2 inhibitors is also associated with reduction in body weight. Modest reductions in blood pressure have been noted with SGLT2 inhibitors, consistent with a mild diuretic action. Some C-glucoside SGLT2 inhibitors, such as dapagliflozin, have pharmacokinetic properties that make them amenable to once-daily dosing.

  16. Coagulation profile in patients undergoing video-assisted thoracoscopic lobectomy

    Christensen, Thomas Decker; Vad, Henrik; Pedersen, Søren

    2017-01-01

    -, and the first two days postoperatively by standard coagulation blood test, thromboelastometry (ROTEM®) and thrombin generation. Results: Patients undergoing potential curative surgery for lung cancer were not hypercoagulable preoperatively. There was no statistically significant difference in the majority......Background: Knowledge about the impact of Low-Molecular-Weight Heparin (LMWH) on the coagulation system in patients undergoing minimal invasive lung cancer surgery is sparse. The aim of this study was to assess the effect of LMWH on the coagulation system in patients undergoing Video......-Assisted Thoracoscopic Surgery (VATS) lobectomy for primary lung cancer. Methods: Sixty-three patients diagnosed with primary lung cancer undergoing VATS lobectomy were randomized to either subcutaneous injection with dalteparin (Fragmin®) 5000 IE once daily or no intervention. Coagulation was assessed pre-, peri...

  17. Topical cetirizine and oral vitamin D: a valid treatment for hypotrichosis caused by ectodermal dysplasia.

    Rossi, A; Miraglia, E; Fortuna, M C; Calvieri, S; Giustini, S

    2017-02-01

    Ectodermal dysplasia is a clinically and genetically heterogeneous group of inherited disorders characterized by abnormal development of two or more of the following ectodermal-derived structures: hair, teeth, nails and sweat glands. The hair is the most frequently affected structure. Hair shaft abnormalities are of great concern to these patients, but no effective treatments are available. We describe three girls with congenital hypotrichosis (9, 5 and 6 years old) caused by ectodermal dysplasia treated with topical cetirizine solution (2 mL. once daily) and oral vitamin D supplementation (1000 IU daily). After 6 months of treatment, the density of hair on the scalp increased in all patients. The vellus hair was replaced by terminal hair. Hair regrowth was evaluated both from the clinical and trichoscopic point of view. We propose a combination of topical cetirizine and oral vitamin D as a rational treatment of choice in congenital hypotrichosis caused by ectodermal dysplasia. © 2016 European Academy of Dermatology and Venereology.

  18. Repeated intraperitoneal injections of interleukin 1 beta induce glucose intolerance in normal rats

    Wogensen, L; Reimers, J; Mandrup-Poulsen, T

    1991-01-01

    Previous in vitro findings suggest the involvement of interleukin 1 (IL-1) in the pathogenesis of insulin-dependent diabetes mellitus. The aims of the present study were to investigate the effects of single or repeated ip injections of recombinant IL-1 beta on blood glucose and glucose tolerance...... in vivo. Normal Wistar Kyoto rats were injected ip with a single injection of 4 micrograms/kg of the mature form of recombinant IL-1 beta (amino acids 117-269) or once daily on 5 consecutive days. Control rats were given vehicle and were fed ad libitum or pair-fed together with the rIL-1 beta treated rats...... in food intake, a lasting mild depression of blood glucose (7 days) and a transiently impaired glucose tolerance on day 5. We conclude that systemic IL-1 should be considered an important regulator of glucose homeostasis in vivo....

  19. The developmental stage of strongyle eggs affects the outcome of real-time PCR analysis

    Roust, Tina; Haakansson, Ida T.; Rhod, Maria

    Several molecular diagnostic tests are based upon measuring and quantifying DNA obtained from parasite eggs. It is well-known that such eggs undergo development during storage, but it remains unknown to which extent the stage of development can affect the diagnostic test result. This project...... investigated whether the developmental stage of strongyle eggs affects real-time polymerase chain reaction (PCR) results. Mixed species strongyle eggs were obtained from the faeces of a naturally infected horse. Eggs were isolated and placed in microtiter plates with demineralised water. A total of 25 wells...... containing 100 eggs each were set up and kept refrigerated for up to five days. Once daily, five wells were microscopied on an inverted microscope, the developmental stages of the eggs were noted, and the eggs harvested for DNA extraction. The protocol was repeated three times. Genomic DNA was extracted...

  20. Bilateral akillesseneruptur efter behandling med ciprofloxacin

    Attarzadeh, Amir Pasha; Ryge, Camilla

    2013-01-01

    We report a case of spontaneous non-traumatic bilateral rupture of the Achilles tendons following ciprofloxacin treatment. A 54-year-old man presented with spontaneous Achilles tendon rupture on the left side, tendinitis and partial tear on the right side following few days of treatment with cipr......We report a case of spontaneous non-traumatic bilateral rupture of the Achilles tendons following ciprofloxacin treatment. A 54-year-old man presented with spontaneous Achilles tendon rupture on the left side, tendinitis and partial tear on the right side following few days of treatment...... with ciprofloxacin 500 mg twice daily and long-term treatment with prednisolon 10 mg once daily. This rare side effect caused by concurrent treatment with steroids and ciprofloxacin should be kept in mind. Any signs of tendinitis following this treatment should arouse the physicians' suspicion towards ciprofloxacin....