BACKGROUND:Valsartan is a selective angiotensin II type 1 receptor blocker indicated for the treatment of hypertension. Although the bioavailability and pharmacokinetic properties of valsartan have been well characterized, a literature search did not identify any reports concerning the bioavailability of valsartan in the Indian population. OBJECTIVE: This study was undertaken to compare the pharmacokinetic properties of 2 branded generic valsartan formulations (tests A and B) with a branded innovator product (reference) in healthy Indian male subjects. METHODS: This single-dose, randomized, open-label, 3-period crossover study compared the pharmacokinetic properties of 3 marketed brands of valsartan 160-mg tablets in healthy Indian male volunteers aged 18 to 45 years under fasting conditions. Subjects were assigned to receive, in randomized order, a single oral dose of 1 of 2 test formulations (A or B) or a reference formulation of valsartan 160 mg. Each study period was separated by a 5-day washout period. Blood samples were collected at prespecified times over a period of 24 hours after administration. An HPLC method was used for the estimation of plasma valsartan concentrations. A noncompartmental method was employed to determine the pharmacokinetic properties (C(max), T(max), AUC(0-t), AUC(0-infinity), and t(1/2)) to test for bioequivalence. The predetermined regulatory range of 90% CI for bioequivalence was 80% to 125%. Tolerability was assessed using physical examination, including vital sign measurement, and direct questioning. RESULTS: The study was conducted in 18 subjects (mean age, 24.8 years; weight, 54.5 kg; and height, 164.67 cm). For test formulation A versus the reference formulation, the 90% CIs of the least squares mean test/reference ratios of C(max), AUC(0-t), and AUC(0-infinity) were 81.18% to 115.74%, 77.27% to 108.75%, and 79.32% to 108.70%, respectively. For test B versus reference, the corresponding values were 84.69% to 120.73%, 83.72% to 117.84%, and 84.40% to 115.67%. No adverse events were found or reported by subjects throughout the study. CONCLUSIONS: In this single-dose study in a small sample of healthy Indian male subjects, test formulation B of valsartan 160 mg was considered bioequivalent to the reference formulation as per predetermined regulatory criteria, whereas test formulation A was not. All 3 formulations were well tolerated. Copyright 2010 Excerpta Medica Inc. All rights reserved.
RCT Entities:
BACKGROUND:Valsartan is a selective angiotensin II type 1 receptor blocker indicated for the treatment of hypertension. Although the bioavailability and pharmacokinetic properties of valsartan have been well characterized, a literature search did not identify any reports concerning the bioavailability of valsartan in the Indian population. OBJECTIVE: This study was undertaken to compare the pharmacokinetic properties of 2 branded generic valsartan formulations (tests A and B) with a branded innovator product (reference) in healthy Indian male subjects. METHODS: This single-dose, randomized, open-label, 3-period crossover study compared the pharmacokinetic properties of 3 marketed brands of valsartan 160-mg tablets in healthy Indian male volunteers aged 18 to 45 years under fasting conditions. Subjects were assigned to receive, in randomized order, a single oral dose of 1 of 2 test formulations (A or B) or a reference formulation of valsartan 160 mg. Each study period was separated by a 5-day washout period. Blood samples were collected at prespecified times over a period of 24 hours after administration. An HPLC method was used for the estimation of plasma valsartan concentrations. A noncompartmental method was employed to determine the pharmacokinetic properties (C(max), T(max), AUC(0-t), AUC(0-infinity), and t(1/2)) to test for bioequivalence. The predetermined regulatory range of 90% CI for bioequivalence was 80% to 125%. Tolerability was assessed using physical examination, including vital sign measurement, and direct questioning. RESULTS: The study was conducted in 18 subjects (mean age, 24.8 years; weight, 54.5 kg; and height, 164.67 cm). For test formulation A versus the reference formulation, the 90% CIs of the least squares mean test/reference ratios of C(max), AUC(0-t), and AUC(0-infinity) were 81.18% to 115.74%, 77.27% to 108.75%, and 79.32% to 108.70%, respectively. For test B versus reference, the corresponding values were 84.69% to 120.73%, 83.72% to 117.84%, and 84.40% to 115.67%. No adverse events were found or reported by subjects throughout the study. CONCLUSIONS: In this single-dose study in a small sample of healthy Indian male subjects, test formulation B of valsartan 160 mg was considered bioequivalent to the reference formulation as per predetermined regulatory criteria, whereas test formulation A was not. All 3 formulations were well tolerated. Copyright 2010 Excerpta Medica Inc. All rights reserved.
Authors: Lamberto Manzoli; Maria Elena Flacco; Stefania Boccia; Elvira D'Andrea; Nikola Panic; Carolina Marzuillo; Roberta Siliquini; Walter Ricciardi; Paolo Villari; John P A Ioannidis Journal: Eur J Epidemiol Date: 2015-11-30 Impact factor: 8.082