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Dosing Frequency (dosing + frequency)
Selected AbstractsBioavailability of divalproex extended-release formulation relative to the divalproex delayed-release formulationBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 8 2004Sandeep Dutta Abstract Divalproex sodium extended-release tablet (divalproex-ER) is a novel formulation of the conventional divalproex sodium delayed-release tablet (divalproex). In five multiple-dose studies in healthy subjects (n=82) and epilepsy patients (n=86) the estimates of divalproex-ER/divalproex ratios for steady-state 24 h valproic acid area under the curve (AUC) central values, maximum concentration (Cmax) central values and minimum concentration (Cmin) means had ranges of 0.77,0.97, 0.71,0.87 and 0.78,1.03, respectively. These studies used different divalproex regimens (two, three or four times daily) and meal conditions (fasting, low, medium and high calorie meals). Divalproex-ER was administered once daily. A meta-analysis of divalproex-ER/divalproex relative bioavailability across five studies under different meal conditions and divalproex dosing frequencies was performed. This meta-estimate of relative bioavailability was used to provide dosing recommendations for conversion of patients from divalproex to divalproex-ER. The estimated AUC, Cmax and Cmin divalproex-ER/divalproex ratios (95% confidence interval) were 0.89 (0.85,0.94), 0.79 (0.74,0.84) and 0.96 (0.90,1.02), respectively. The food and divalproex regimen had no effect on the relative bioavailability. While switching from divalproex to divalproex-ER, the divalproex-ER daily dose may have to be increased by an average of 12% (calculated as 1.0/0.89) to achieve comparable plasma exposure. Since the divalproex-ER dosage strengths (250 and 500 mg) are not 12% higher than the divalproex dosage strengths (125, 250 and 500 mg), an 8% to 20% higher divalproex-ER daily dose should be considered for conversion from divalproex to divalproex-ER. Copyright © 2004 John Wiley & Sons, Ltd. [source] Osteoporosis medication profile preference: results from the PREFER-US studyHEALTH EXPECTATIONS, Issue 3 2007Thomas W. Weiss DrPH Abstract Objective, To assess patient preferences for two osteoporosis medications. Design, Women aged 50+ were surveyed via the Internet to assess preferences for two osteoporosis medication profiles. Drug A and Drug B, consistent with ibandronate and alendronate, respectively, differed by: time on market (recently vs. 10 years), dosing frequency (monthly vs. weekly), effectiveness (not proven vs. proven to reduce non-spine or hip fracture after 3 years) and dosing procedure (60 vs. 30 min wait before eating/drinking). Each profile had the same out-of-pocket costs, side-effects, potential for drug interaction and spine fracture efficacy. Patients force ranked and rated the importance of each attribute. Subgroup comparisons included diagnosed vs. at-risk respondents and treated vs. untreated respondents. Results, Among the 999 respondents, Drug B was preferred by 96%. Effectiveness was ranked as the most important determinant of preference (79% ranked it #1) compared with time on market (14%), dosing procedure (4%) and dosing frequency (3%). Effectiveness had the highest mean importance rating on a scale of 1 (extremely unimportant) to 7 (extremely important): mean (SD) = 6.1 (1.8), followed by time on market: 4.7 (1.7), dosing procedure: 4.6 (1.4) and dosing frequency: 4.5 (1.4). No significant differences in profile choice were found across study subgroups. Conclusions, The drug profile showing reductions in non-vertebral and hip fracture risk was chosen by almost all respondents. Drug effectiveness was the most important determinant of preference, while dosing frequency was the least important determinant. Incorporation of patient preferences in the medication decision-making process could enhance patient compliance and clinical outcomes. [source] Monthly Oral Ibandronate Therapy in Postmenopausal Osteoporosis: 1-Year Results From the MOBILE StudyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2005Paul D Miller MD Abstract Once-monthly (50/50, 100, and 150 mg) and daily (2.5 mg; 3-year vertebral fracture risk reduction: 52%) oral ibandronate regimens were compared in 1609 women with postmenopausal osteoporosis. At least equivalent efficacy and similar safety and tolerability were shown after 1 year. Introduction: Suboptimal adherence to daily and weekly oral bisphosphonates can potentially compromise therapeutic outcomes in postmenopausal osteoporosis. Although yet to be prospectively shown in osteoporosis, evidence from randomized clinical trials in several other chronic conditions shows that reducing dosing frequency enhances therapeutic adherence. Ibandronate is a new and potent bisphosphonate with antifracture efficacy proven for daily administration and also intermittent administration with a dose-free interval of >2 months. This report presents comparative data on the efficacy and safety of monthly and daily oral ibandronate regimens. Materials and Methods: MOBILE is a 2-year, randomized, double-blind, phase III, noninferiority trial. A total of 1609 women with postmenopausal osteoporosis were assigned to one of four oral ibandronate regimens: 2.5 mg daily, 50 mg/50 mg monthly (single doses, consecutive days), 100 mg monthly, or 150 mg monthly. Results: After 1 year, lumbar spine BMD increased by 3.9%, 4.3%, 4.1%, and 4.9% in the 2.5, 50 /50, 100, and 150 mg arms, respectively. All monthly regimens were proven noninferior, and the 150 mg regimen superior, to the daily regimen. All monthly regimens produced similar hip BMD gains, which were larger than those with the daily regimen. All regimens similarly decreased serum levels of C-telopeptide, a biochemical marker of bone resorption. Compared with the daily regimen, a significantly larger proportion of women receiving the 100 and 150 mg monthly regimens achieved predefined threshold levels for percent change from baseline in lumbar spine (6%) or total hip BMD (3%). All regimens were similarly well tolerated. Conclusions: Monthly ibandronate is at least as effective and well tolerated as the currently approved daily ibandronate regimen in postmenopausal osteoporosis. [source] Infliximab improves inflammation and anthropometric measures in pediatric Crohn's diseaseJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2010Daniel M Sinitsky Abstract Background and Aim:, Infliximab (IFX) is a monoclonal antibody licensed to treat medically refractory Crohn's disease (CD). Our aim was to elucidate the effects of IFX therapy on clinical, growth and serum parameters in children with CD in a single pediatric center in Sydney, Australia. Methods:, A retrospective case series review of children treated with IFX for CD at Sydney Children's Hospital, Australia was undertaken, with a review of outcomes after starting IFX. Main outcome measures were response and remission (as measured according to improvements in Pediatric Crohn's Disease Activity Index scores and Physician Global Assessment), laboratory markers (C-reactive protein, erythrocyte sedimentation rate, hemoglobin, white cell count, lymphocytes, neutrophils, platelets, albumin) and growth (Z scores). Results:, The 16 patients included had a mean age at first infusion of 13.0 years (1.25,17.5 years). Six of 12 patients (with adequate data available) were in remission at 2 weeks following the first infusion. At 1 year, 10 of 12 patients (83%) were in remission. Mean C-reactive protein and erythrocyte sedimentation rate had fallen significantly (P < 0.05) at 2 weeks (from 29 to 7 mg/L and 40 to 19 mm/h, respectively). Positive trends were observed for all other parameters, excluding lymphocytes and white cell count. At 1 year, mean Z score for body mass index improved significantly from ,0.9 to ,0.1 (P < 0.01). Conclusions:, Disease activity subsides in most children treated with IFX for CD. IFX therapy also improves some growth parameters. The pattern of improvement requires further elucidation, as the results in the present study suggest differing dosing frequency of infusion may achieve better efficacy. [source] Searching for the Intervention in Intervention Research ReportsJOURNAL OF NURSING SCHOLARSHIP, Issue 1 2008Vicki S. Conn Purpose: Precisely described interventions in nursing research reports are essential as a foundation for nursing practice and to facilitate future research. The purpose of this project was to characterize the intervention descriptions in nursing intervention research reports. Design and Methods: Quantitative content analysis was used to analyze intervention descriptions in reports published in English-language general nursing journals during 2005. Normative analysis was used to examine reports for details related to intervention content and delivery. Physical unit analysis was used to compare relative amounts of article space devoted to intervention description vs. other methodological details. Findings: Results were tabulated for 141 research articles published in 27 journals. Analysis indicated incomplete reporting of intervention details in many articles. Dose and dosing frequency were rarely completely defined. Delivery setting and interventionist were frequently not indicated, and the professional credentials of nurse interventionists were often unclear. While descriptions of interventions involving substances or devices were typically detailed, the specifics of psychological, educational, behavioral, and systems-level interventions were often lacking. Intervention descriptions averaged 7.27% of total article space, whereas nonintervention methodological descriptions averaged 20.74% of space. Of studies examined, only 38 (27.0%) reported enough detail to potentially replicate the study or translate the intervention into practice. Conclusions: Intervention descriptions in general nursing journals lack sufficient detail to provide the evidence basis for practice. [source] Inhalable liposomes of low molecular weight heparin for the treatment of venous thromboembolismJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2010Shuhua Bai Abstract This study tests the feasibility of inhalable pegylated liposomal formulations of low molecular weight heparin (LMWH) for treatment of two clinical manifestations of vascular thromboembolism: deep vein thrombosis (DVT) and pulmonary embolism (PE). Conventional distearoyl- sn -glycero-3-phosphoethanolamine (DSPE) and long-circulating pegylated (DSPE,PEG-2000 and DSPE,PEG-5000) liposomes were prepared by hydration method. Formulations were evaluated for particle size, entrapment efficiency, stability, pulmonary absorption, anticoagulant, and thrombolytic effects in rats. Pulmonary absorption was monitored by measuring plasma antifactor Xa activity; anticoagulant and thrombolytic effects were studied by measuring reduction in thrombus weight and amount of dissolved radioactive clot in the blood, respectively. Pegylated liposomal were smaller and showed greater drug entrapment efficiency than conventional liposomes. All formulations produced an increase in pulmonary absorption and circulation time of LMWH upon first dosing. Three repeated dosings of conventional liposomes resulted in decreased half-life and bioavailability; no changes in these parameters were observed with pegylated liposomes. PEG-2000 liposomes were effective in reducing thrombus weight when administered every 48,h over 8 days. In terms of thrombolytic effects and dosing frequency, PEG-2000 liposomes administered via the pulmonary route at a dose of 100,U/kg were as effective as 50,U/kg LMWH administered subcutaneously. This paper suggests that inhalable pegylated liposomes of LMWH could be a potential noninvasive approach for DVT and PE treatment. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:4554,4564, 2010 [source] Advances and potential applications of chitosan derivatives as mucoadhesive biomaterials in modern drug deliveryJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2006Shruti Chopra Pharmaceutical technologists have been working extensively on various mucoadhesive polymeric systems to create an intimate and prolonged contact at the site of administration. Chitosan is one of the most promising polymers because of its non-toxic, polycationic biocompatible, biodegradable nature, and particularly due to its mucoadhesive and permeation enhancing properties. Due to its potential importance in controlled drug delivery applications, pharmaceutical scientists have exploited this mucoadhesive polymer. However, chitosan suffers from limited solubility at physiological pH and causes presystemic metabolism of drugs in intestinal and gastric fluids in the presence of proteolytic enzymes. These inherent drawbacks of chitosan have been overcome by forming derivatives such as carboxylated, various conjugates, thiolated, and acylated chitosan, thus providing a platform for sustained release formulations at a controlled rate, prolonged residence time, improved patient compliance by reducing dosing frequency, enhanced bioavailability and a significant improvement in therapeutic efficacy. We have explored the potential benefits of these improved chitosan derivatives in modern drug delivery. [source] Treatment of ulcerative colitis from the patient's perspective: a survey of preferences and satisfaction with therapyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2009J. R. GRAY Summary Background, Data available regarding patient perspectives on ulcerative colitis (UC) and their preferences and satisfaction with therapy are limited. Aims, To examine the preferences of UC patients to understand better what they look for in a therapy when managing their disease, as this may influence overall medication adherence. Methods, The study surveyed 100 Canadian UC patients on topics including educational resources used to learn about the disease, medication attributes that are most valued and preferred by the patient and satisfaction with current therapy. Results, Overall, efficacy- and safety-related medication attributes were rated by patients to be more important than those related to dosing regimen (e.g. dosing frequency, number of pills), cost and formulary coverage. In pair-wise comparisons of specific medication attributes, UC patients rated speed of symptom relief and few side effects as the most important factors when considering a UC medication (preferred on average 84% and 74% of the time respectively). Conclusion, This study provides insight into UC patient preferences and satisfaction with therapy that may be important when counselling on treatment options, and generates relevant discussions on adherence. Larger studies may be warranted to examine further how these findings can be extrapolated to broader UC populations. [source] Review article: medication non-adherence in ulcerative colitis , strategies to improve adherence with mesalazine and other maintenance therapiesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2008A. B. HAWTHORNE Summary Background, Significant number of patients with ulcerative colitis (UC) fail to comply with treatment. Aims, To review issues surrounding medication non-adherence in inflammatory bowel disease (IBD), including the clinical and health service implications in the UK, and discuss strategies for optimizing medication adherence. Methods, Articles cited were identified via a PubMed search, utilizing the words IBD, adherence, compliance, medication and UC. Results, Medication non-adherence is multifactorial involving factors other than dosing frequency. Male gender (OR: 2.06), new patient status (OR: 2.14), work and travel pressures (OR: 4.9) and shorter disease duration (OR: 2.1), among others are proven predictors of non-adherence in UC. These indicators can identify ,at-risk' patients and allow an individually tailored treatment approach to be introduced that optimizes medication adherence. A collaborative relationship between physician and patient is important; several strategies for improving adherence have been proven effective including open dialogue that takes into consideration the patient's health beliefs and concerns, providing educational (e.g. verbal/written information, self-management programmes) and behavioural interventions (e.g. calendar blister packs, cues/reminders). Conclusions, Educational and behavioural interventions tailored to individual patients can optimize medication adherence. Additional studies combining educational and behavioural interventions may provide further strategies for improving medication adherence rates in UC. [source] Treatment with inhaled corticosteroids in asthma is too often discontinued,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 4 2008Nancy S. Breekveldt-Postma PhD Abstract Purpose To study persistence with inhaled corticosteroids (ICS) and its determinants in asthma-patients. Methods From the PHARMO database, asthma-patients (age,<,35 years) with a first dispensing for ICS in 1999,2002 and,,,2 dispensings in the first year were included. Persistence during the first year was defined as the number of days from start to time of first failure to continue renewal of the initial ICS. Potential determinants of persistence were assessed at ICS-start and 1 year before. Results The study-cohort included 5563 new users of single ICS and 297 of fixed-combined ICS. Less than 10% of patients using single ICS and 15% of patients using fixed-combined ICS were persistent at 1 year. Similar persistence-rates were observed when stratified for age (children/adolescents: 0,18 years and adults: 19,34 years). Increased persistence with single ICS was observed with the type of ICS (budesonide), prescriber (specialist), prior use of long-acting beta-agonists, previous hospitalization for asthma, metered-dose inhaler, low starting-dose and once-daily dosing regimen at start. Persistence with fixed combined ICS-treatment increased with younger age and was decreased in patients having high starting-dose of ICS and prior use of antibiotics. Conclusion New users of both single and fixed combined ICS have alarming low persistence rates with ICS-treatment in the first year of follow-up. Persistence was mainly related to patient factors, such as severity of disease, and to treatment-related factors, such as once-daily dosing frequency. Copyright © 2008 John Wiley & Sons, Ltd. [source] Effect of dosing frequency on the safety and efficacy of imiquimod 5% cream for treatment of actinic keratosis on the forearms and hands: a phase II, randomized placebo-controlled trialBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2009K. Gebauer Summary Background, Clinical studies in cutaneous conditions other than actinic keratosis (AK) have revealed that the safety and efficacy profile of imiquimod is influenced by dosing frequency. Objectives, To evaluate dosing frequency response of imiquimod 5% for treatment of AK. Methods, This was a phase II, multicentre, randomized, double-blind, placebo-controlled study. Adults with , 10 but , 50 clinical AKs, one of which was histologically confirmed, were randomized (4 : 1) to 2,6 packets of imiquimod or placebo cream applied to the dorsum of the forearms and hands once daily 2, 3, 5 or 7 times per week for 8 weeks. The primary endpoint was complete clearance of AKs in the treatment area at 8 weeks post-treatment. Results, One hundred and forty-nine (94 men and 54 women) white subjects, with a mean ± SD age of 71 ± 10·2 years, were enrolled. Twenty-eight subjects (18·8%) discontinued from study: 0%, 3·1%, 6·9%, 30·0% and 33·3% withdrew for local skin reactions or adverse events in the combined placebo, and in the imiquimod 2, 3, 5 or 7 times per week groups, respectively. Seven serious adverse events occurred; none was related to the study drug. Median baseline lesions ranged from 38 to 40 for the treatment groups. Complete clearance was achieved in 0%, 3·2%, 6·9%, 3·3% and 6·7% of subjects, and partial clearance (, 75% lesion reduction) in 0%, 22·6%, 24·1%, 20·0% and 36·7% of subjects for the placebo and imiquimod 2, 3, 5 or 7 times per week regimens, respectively. Conclusions, Imiquimod 5% applied more frequently than 3 times per week to AKs was not well tolerated. Complete clearance rates were low; however, partial clearance rates increased with increased dosing frequency (P = 0·002). [source] The experimental Alzheimer drug phenserine: preclinical pharmacokinetics and pharmacodynamicsACTA NEUROLOGICA SCANDINAVICA, Issue 2000N. H. Greig Phenserine, a phenylcarbamate of physostigmine, is a new potent and highly selective acetylcholinesterase (AChE) inhibitor, with a >50-fold activity versus butyrylcholinesterase (BChE), in clinical trials for the treatment of Alzheimer's disease (AD). Compared to physostigmine and tacrine, it is less toxic and robustly enhances cognition in animal models. To determine the time-dependent effects of phenserine on cholinergic function, AChE activity, brain and plasma drug levels and brain extracellular acetylcholine (ACh) concentrations were measured in rats before and after phenserine administration. Additionally, its maximum tolerated dose, compared to physostigmine and tacrine, was determined. Following i.v. dosing, brain drug levels were 10-fold higher than those achieved in plasma, peaked within 5 min and rapidly declined with half-lives of 8.5 and 12.6 min, respectively. In contrast, a high (>70%) and long-lasting inhibition of AChE was achieved (half-life >8.25 h). A comparison between the time-dependent plasma AChE inhibition achieved after similar oral and i.v. doses provided an estimate of oral bioavailability of 100%. Striatal, in vivo microdialysis in conscious, freely-moving phenserine-treated rats demonstrated >3-fold rise in brain ACh levels. Phenserine thus is rapidly absorbed and cleared from the body, but produces a long-lasting stimulation of brain cholinergic function at well tolerated doses and hence has superior properties as a drug candidate for AD. It selectively inhibits AChE, minimizing potential BChE side effects. Its long duration of action, coupled with its short pharmacokinetic half-life, reduces dosing frequency, decreases body drug exposure and minimizes the dependence of drug action on the individual variations of drug metabolism commonly found in the elderly. [source] Serum testosterone and bioavailable testosterone correlate with age and body size in hypogonadal men treated with testosterone undecanoate (1000 mg IM , Nebido®)CLINICAL ENDOCRINOLOGY, Issue 4 2008Robert Moisey Summary Objective, To investigate the loading regimen for intramuscular (IM) testosterone undecanoate (Nebido®) to determine whether testosterone and bioavailable testosterone levels achieved correlate with age or body size of subjects studied. Design, Retrospective observational study of testosterone naïve patients and patients previously treated with an alternative testosterone therapy. Patients, 51 hypogonadal men (35, 68·6% secondary hypogonadism). 8 (16%) had not previously received testosterone therapy. Measurements, Patients received an IM injection of Nebido (1000 mg) at baseline and a second injection after 6 weeks. Serum was assayed at baseline and 18 weeks after commencing Nebido for total testosterone (TT) and SHBG. Bioavailable testosterone was calculated (cBioT) using TT and SHBG. Measurements were taken for weight, body mass index (BMI) and body surface area (BSA). Results, Baseline TT (mean 11·5 nmol/l, range 0·3,54·8) increased by 50% after commencing Nebido (17·2 nmol/l (5·4,32·8), P = 0·0001). 75% of subjects had a TT within the reference range (8·0,25·0 nmol/l). Subjects with primary hypogonadism had a higher 18-week TT [20·9 nmol/l (9·8,32·8) vs. 15·5 (5·4,32·6), P = 0·02] and SHBG [39·2 nmol/l (11,82) vs. 25·7 (9·0,60·0), P = 0·003] although the cBioT was not significantly different [4·9 nmol/l (2·9,7·3) vs. 4·2 (2·0,7·9), P = 0·12]. The 18-week TT positively correlated with age (R = 0·36, P = 0·01) and negatively correlated with weight (R = ,0·38, P = 0·006), BMI (R = ,0·42, P = 0·002) and BSA (R =,0·38, P = 0·007). Similarly cBioT correlated with age (R = 0·28, P = 0·04), weight (R = ,0·29, P = 0·03), BMI (R = ,0·30, P = 0·03) and BSA (R = ,0·27, P = 0·05). Age (t = 2·04, P = 0·05) and baseline testosterone (t = ,9·26, P < 0·0001) were independent variables of the increase in TT at 18 weeks. Conclusion, This starting regimen is simple and provides the majority of men with a TT within the reference range. Age and baseline TT are independent variables of the increase in TT with IM testosterone undecanoate. At week 18 age and body size correlated with the cBioT and TT and this may then be used to estimate dosing frequency for this therapy. [source] | ||||||||||