采用双向交叉设计的齐多夫定 100 毫克胶囊生物等效性研究

Priyanto P
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引用次数: 0

摘要

齐多夫定是一种合成核苷类似物,特别是一种核苷逆转录酶抑制剂(NRTI),可抑制包括艾滋病病毒在内的逆转录病毒的复制。研究目的:本研究旨在确定 PT Kimia Farma Tbk 公司生产的齐多夫定 100 毫克胶囊与葛兰素史克制药公司生产的 Retrovir 100 毫克胶囊在健康受试者体内的生物等效性:研究采用随机、单剂量、开放标签、双向交叉设计(2 个疗程、2 个阶段和 2 个序列),在空腹状态下进行,每个阶段之间有 7 天的冲洗期。参与并完成研究的 32 名成年男女受试者中有 31 人。一名受试者因个人原因从第二阶段退出。受试者收到了研究说明并签署了知情同意书。受试者在接受试验药物和参照药物前至少禁食 8 小时。在以下时间点采集血液样本 15 次:服药后 0 小时(服药前)、0.16、0.33、0.50、0.75、1、1.5、2、2.5、3、4、5、6、8 和 10 小时。血浆中的药物浓度采用 LC-MS/MS 法测定。本研究计算的药代动力学参数为 AUC0-t、AUC0-inf、Cmax、tmax 和 t½,AUC0-t 和 Cmax 的统计区间为 80.00 - 125.00%,90% 置信区间(CI)为 α = 5.00%。结果根据几何平均比和 90% 置信区间 (CI),计算了试验药齐多夫定(BN: G2 1346 J)与参比药 Retrovir(BN: JN8K)的主要药代动力学参数。AUC0-t和Cmax的结果分别为101.65%(96.77-106.83%)和95.63%(84.09-108.76%),AUC0-t和Cmax的受试者内变异率(%CV)分别为11.49%和30.47%。因此,31 名受试者的数量足以满足研究的需要。结论根据 AUC0-t 和 Cmax 值,由 PT.Kimia Farma Tbk 公司生产的齐多夫定 100 毫克胶囊与葛兰素史克制药公司生产的 Retrovir 100 毫克胶囊具有生物等效性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Bioequivalence Study of Zidovudine 100 Mg Capsule with TwoWay Crossover Design
Zidovudine is a synthetic nucleoside analogue, specifically a nucleoside reverse transcriptase inhibitor (NRTI), that inhibits the replication of retroviruses, including HIV. Study Objective: This study objective was to determine the bioequivalence of Zidovudine 100 mg capsules produced by PT Kimia Farma Tbk compared to Retrovir 100 mg capsules produced by GlaxoSmithKline Pharmaceuticals S.A, in healthy subjects Methods: The study was conducted in a randomized, single-dose, open-label, two-way crossover design (2 treatments, 2 periods, and 2 sequences) under fasting state with 7 (seven) days washed-out period between each period. The number of subjects who participated and completed the study were 31 of 32 adult male and female. One subject dropped out from 2nd period because of personal reason. The subjects received an explanation of the study and signed informed consent. Subjects fasted for a minimum of 8 hours before receiving the test drug and reference drug. Blood samples were collected 15 times at the following time points: 0 hours (before drug administration), 0.16, 0.33, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 10 hours after drug administration. Plasma concentrations of the drug were determined by LC-MS/MS method. The pharmacokinetic parameters calculated in this study are AUC0-t, AUC0-inf, Cmax, tmax, and t½, while the statistical interval proposed was 80.00 - 125.00% for AUC0-t and Cmax with 90% Confidence Interval (CI) with α = 5.00%. Results: The main pharmacokinetic parameters of the test drug Zidovudine (BN: G2 1346 J) compared to reference drug, Retrovir (BN: JN8K) were calculated based on geometric mean ratio and 90% confidence interval (CI). The results for AUC0-t and Cmax were 101.65% (96.77- 106.83%) and 95.63% (84.09-108.76%) respectively, with intra-subject variability (%CV) for AUC0-t and Cmax were 11.49% and 30.47%. Hence, the number of 31 subjects has adequate number for required power of study. Conclusion: Based on the AUC0-t and Cmax values, Zidovudine 100 mg Capsules Produced by PT. Kimia Farma Tbk is bioequivalent to Retrovir 100 mg Capsules Produced by GlaxoSmithKline Pharmaceuticals S.A.
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