Reference values for peak expiratory flow in Indian adult population using a European Union scale peak flow meter.

BACKGROUND: Reference values of peak expiratory flow (PEF) in Indian adults have to date been derived locally, using an old (Wright) scale peak flow meter. There are thus no reliable reference values for PEF for Indians and this formed the aim of the study. MATERIALS AND METHODS: A European Union (EU) scale peak flow meter (PFM) was used for the study. A respiratory health and demographic questionnaire was administered to 1000 male and female adults from randomly selected locations in the country in this multi centric study. The locations represented different geographic, ethnic, and socioeconomic backgrounds. Patients were stratified according to height and age. The PEF values were measured using the Breathometer™ (Cipla Ltd., India) with EU scale. Reference equations were derived from multiple regression analysis. RESULTS: A total of 3608 participants were excluded. In 80% of the remaining 6138 healthy adults (M: 3720; F: 2418), the predicted regression equations were derived. Gender, age, and height were the significant determinants of PEF. The equations in L/minute are: Females: PEF = -1.454 (Age) + 2.368 (Height) Males: PEF = -1.807 (Age) + 3.206 (Height). The derived equation was validated by comparing the predicted PEF values with the measured values in the remaining sample of 20% (Mean ΔPEF: M = 1.85 L/minute, CI = -2.76, 6.47; F = 1.64, CI = -2.89, 6.18). An Indian adult with average height and age was found to have approximately 30% lower PEF compared to the corresponding European adult using the Nunn and Gregg equation. CONCLUSION: We derived reference values of PEF for Indian adults using a validated EU scale peak flow meter.

Tiotropium administered by a pressurized metered dose inhaler (pMDI) and spacer produces a similar bronchodilator response as that administered by a Rotahaler in adult subjects with stable moderate-to-severe COPD.

BACKGROUND: Tiotropium is a new long-acting anticholinergic bronchodilator, which is recommended as first-line therapy in the management of chronic obstructive pulmonary disease (COPD). It is currently available in the form of a dry powder inhaler worldwide. Some COPD patients find it difficult to generate inspiratory flow rates of up to 40 l/min, which is required for the drug to reach the airways. To overcome this, a new pMDI form has been developed for administration of tiotropium in patients with COPD. The clinical efficacy of this mode of tiotropium delivery has, so far, not been compared with the currently available dry powder inhaler (DPI) devices. AIMS AND OBJECTIVES: To compare the bronchodilator effects of a single dose of 18 mcg of tiotropium administered via a pressurized meter dose inhaler (pMDI) and spacer with the currently available DPI form through Rotahaler. STUDY DESIGN: A randomized, double-blind, double-dummy, three-period, placebo-controlled, crossover, single-center study was conducted in 19 patients with stable COPD. Single doses of tiotropium (18 mcg) or placebo were administered on three separate study days (4-7 days apart) through a Rotahaler and pMDI with a non-static spacer (Zerostat, Cipla Ltd.). During each study visit forced expiratory volume in 1s (FEV(1)) and forced vital capacity (FVC) were measured over a period of 24 h at 11 different time points (0, 15, 30 min, 1, 2, 3, 4, 6, 8, 12 and 24h), using a bellows spirometer (Vitalograph) 2160, UK) while static parameters like inspiratory capacity (IC), residual volume (RV), intrathoracic gas volume (ITGV) and total lung capacity (TLC) were measured by bodyplethysmography (Jaeger Masterscreen, Germany) at 0 min, 3, 8 and 24 h. RESULTS: Tiotropium administered through both pMDI (and spacer) and DPI showed significantly better mean FEV(1) and mean FVC differences from baseline, in terms of mean maximum change and area under curve over a period of 24 h (AUC(0-24 h)), as compared to placebo. The mean IC and trough FEV(1) values also improved significantly with tiotropium administered through both the devices as compared to placebo. For all these parameters, there was no difference in the efficacy between pMDI and DPI. There was also no significant difference between the time to onset, time to maximum response and duration of response between tiotropium administered through both the study devices. On the other hand, there was no significant difference in RV, ITGV and TLC by a single dose of tiotopium delivered through either of the devices when compared with placebo over a period of 24 h. CONCLUSION: This is the first study to demonstrate that tiotropium administered by pMDI and spacer shows a superior time-dependent bronchodilator response when compared to placebo, and that this therapeutic efficacy is similar to tiotropium administered by DPI. We recommend the use of tiotropium administered through a pMDI and spacer to those COPD patients who prefer to use the pMDI device, and especially in those who cannot generate sufficient inspiratory flows required for dry powder inhaler devices.

Aerosol delivery systems in childhood asthma.

Asthma in younger children appears to be increasing in prevalence, whilst at the same time it is recognized that inhaled corticosteroids and bronchodilators are the mainstay of treatment for this condition. Presently the devices available for aerosol treatment of young children are mostly developed for use in older children and adults. However, an awareness of the need for delivery systems dedicated to use by young children is increasing. The devices available at present for aerosol treatment of young children comprises the nebulizer, metered-dose inhaler with spacer, and dry powder inhaler. The inhaler strategy found most useful at present can be summarized as follows: children younger than 2 years can use MDI+spacer+mask or nebulization, while children above 2 years can use MDI+spacer (without mask). Older children (3-4 years) can be easily taught the use of a Rotahaler.

Bioequivalence and tolerability study of two brands of clopidogrel tablets, using inhibition of platelet aggregation and pharmacodynamic measures.

BACKGROUND: The role of platelets in acute cardiovascular atherothrombotic events has been well established and attention has focused on platelet inhibition therapy. Clopidogrel is a novel thienopyridine inhibitor of adenosine diphosphate-induced platelet activation. Recent studies have shown that in the setting of coronary angioplasty/stenting, a loading dose of 300 mg followed by 75 mg once daily is required for optimum benefit. OBJECTIVE: This study assessed the bioequivalence and tolerability of 2 oral formulations of clopidogrel 75-mg tablets. METHODS: This 10-day, open-label, randomized, parallel-group, comparative bioequivalence and tolerability study was carried out in the Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences (Hyderabad, India). Young healthy male volunteers were enrolled. Subjects were randomized to receive one of two 75-mg tablet formulations of clopidogrel (Clopivas(®) [test formulation] or Plavix(®) [reference formulation]). Subjects first received a 300-mg loading dose (four 75-mg tablets) on day 1, followed by 75 mg (1 tablet) at 8:00 AM daily for the next 6 days. Inhibition of platelet aggregation, which is the pharmacologic basis for the therapeutic efficacy of antiplatelet agents, and the effect on bleeding time were used as the pharmacodynamic assessment criteria. Pharmacodynamic variables included mean of maximum activity of percentage of inhibition of platelet aggregation (Emax), mean time to reach Emax (tmax), and mean area under the activity-time curve from time 0 to 168 hours (AUC0-168). Tolerability assessments included blood pressure and heart rate measurements before and at regular intervals (every hour for 12 hours and then at 24 hours) over a 24-hour period after drug administration. Clinical tolerability was assessed using adverse effects, platelet count (assessed on days 3, 6, and 10 after first-dose administration), and neutrophil count (assessed on day 10 after first-dose administration). RESULTS: Twenty subjects were enrolled (mean [SD] age, 26.5 [2.9] years [range, 22-32 years]). Emax, tmax, and AUC0-168 were similar between the 2 groups, as was bleeding time. The 90% CIs were within the bioequivalence acceptance range of 80% to 125%. One subject (10%) in the Plavix group experienced mild headache; no serious adverse effects were reported, and none of the subjects dropped out due to an adverse effect. Platelet and neutrophil counts were found to be within normal limits. CONCLUSIONS: In this study of healthy male volunteers, the 2 tablet preparations of clopidogrel showed bioequivalence. However, the sample size was smaller than that generally recommended for a bioequivalence study, and additional studies with larger sample sizes are needed.

Randomised controlled trial of topical butenafine in tinea cruris and tinea corporis.

Butenafine is a new antifungal agent similar to allyl amine antifungals. A randomized controlled trial was conducted in 75 patients to compare its efficacy with clotrimazole in tinea cruris and corporis that was diagnosed on clinical features and demonstration of hyphae in a potassium hydroxide (KOH) preparation. Twenty patients treated with butenafine once daily for 2 weeks and 20 treated with clotrimazole twice daily for 4 weeks were analysed. At the end of treatment, 2 weeks and 4 weeks later, the KOH preparation was negative in 90.9%, 95.5% and 90.9% of patients respectively in the butenafine group and 100%, 96.4% and 92.85% respectively in the clotrimazole group. There was a reduction of 81.5% in the sign and symptom score at 4 weeks following treatment in the butenafine group and 85.93% in the clotrimazole group. There was no statistically significant difference between the two groups. Adverse effects were mild in both groups and did not require discontinuation of therapy except one patient treated with clotrimazole who developed dermatitis at the site of application. Butenafine appears to be as effective as clotrimazole in the treatment of tinea cruris and corporis while requiring a single daily application for a shorter of 2 weeks.