Department of Pharmaceutical Medicine, Hamdard University (Jamia Hamdard), New Delhi, India.
Clin Ther. 2010 Mar;32(3):588-96. doi: 10.1016/j.clinthera.2010.03.004.
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.
背景：缬沙坦是一种选择性血管紧张素 II 型 1 型受体阻滞剂，用于治疗高血压。尽管缬沙坦的生物利用度和药代动力学特性已得到很好的描述，但文献检索并未发现任何关于印度人群中缬沙坦生物利用度的报告。
目的：本研究旨在比较两种品牌仿制药缬沙坦制剂（试验 A 和 B）与品牌创新药物（参比）在健康印度男性中的药代动力学特性。
方法：这是一项单剂量、随机、开放标签、三周期交叉研究，比较了健康印度男性志愿者在禁食条件下服用三种市售品牌缬沙坦 160mg 片剂的药代动力学特性。受试者按随机顺序接受 1 种试验制剂（A 或 B）或缬沙坦 160mg 的参比制剂的单次口服剂量。每个研究期之间有 5 天的洗脱期。给药后 24 小时内按规定时间采集血样。采用 HPLC 法测定血浆缬沙坦浓度。采用非房室法测定药代动力学参数（Cmax、Tmax、AUC（0-t）、AUC（0-∞）和 t1/2）以测试生物等效性。生物等效性的预定监管范围为 90%CI 为 80%至 125%。通过体检、包括生命体征测量和直接询问来评估耐受性。
结果：这项研究在 18 名受试者（平均年龄 24.8 岁；体重 54.5kg；身高 164.67cm）中进行。对于试验制剂 A 与参比制剂，最小二乘均值试验/参比比值的 90%CI 为 Cmax、AUC（0-t）和 AUC（0-∞）分别为 81.18%至 115.74%、77.27%至 108.75%和 79.32%至 108.70%。对于试验 B 与参比，相应值分别为 84.69%至 120.73%、83.72%至 117.84%和 84.40%至 115.67%。在整个研究过程中，受试者均未发现或报告任何不良事件。
结论：在这项针对健康印度男性的单剂量研究中，根据预定的监管标准，缬沙坦 160mg 的试验制剂 B 被认为与参比制剂具有生物等效性，而试验制剂 A 则不然。所有 3 种制剂均具有良好的耐受性。
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