Setiawati Effi, Deniati Siti Hawa, Yunaidi Danang Agung, Handayani Lucia Rat, Harinanto Gunawan, Santoso Iwan Dwi, Sari Asriningtyas Purnomo, Rimainar Atika
PT Equilab International, Bioavailability and Bioequivalence Laboratory, Jakarta, Indonesia.
Arzneimittelforschung. 2009;59(9):471-5. doi: 10.1055/s-0031-1296427.
The study was conducted to find out whether the bioavailability of a 500 mg azithromycin (CAS 83905-01-5) tablet (Zycin, test) was equivalent to that of a reference formulation. The pharmacokinetic parameters assessed in this study were the area under the plasma concentration-time curve from time zero to 120 h (AUCt), area under the plasma concentration-time curve from time zero to infinity (AUCinf), the peak plasma concentration of the drug (Cmax), time needed to achieve the peak plasma concentration (tmax), and the elimination half-life (t1/2). This was a randomized, single blind, two-period, cross-over study which included 18 healthy adult male and female subjects under fasting conditions. In each of the two study periods (separated by a washout of two weeks) a single dose of test or reference drug was administered. Blood samples were taken up to 120 h post dose, the plasma was separated and the concentrations of azithromycin were determined by a LC-MS/MS method. In this study, the mean AUCt, AUCinf, Cmax, and t1/2 of azithromycin from the test drug were 4967.49 ng x h x mL(-1), 5871.74 ng x h x mL(-1), 412.14 ng/mL, and 51.32 h, respectively. The mean AUCt, AUCinf, Cmax, and t1/2 of azithromycin from the reference drug were 4276.75 ng x h x mL(-1), 5578.12 ng x h x mL(-1), 419.89 ng/mL, and 51.23 h, respectively. The median tmax of he test drug and reference drug were 3.0 h and 2.0 h, respectively. The geometric mean ratios (90% CI) of the test drug/reference drug for azithromycin were 101.56% (86.61-119.08%) for AUCt, 101.27% (84.97-120.70%) for AUCinf, and 97.78% (84.50-113.16%) for Cmax. Based on this study, it was concluded that the two azithromycin tablets (test and reference drug) were bioequivalent in terms of the rate and extent of absorption.
本研究旨在确定500毫克阿奇霉素（CAS 83905-01-5）片剂（商品名Zycin，试验制剂）的生物利用度是否等同于参比制剂。本研究中评估的药代动力学参数包括从零至120小时的血浆浓度-时间曲线下面积（AUCt）、从零至无穷大的血浆浓度-时间曲线下面积（AUCinf）、药物的血浆峰浓度（Cmax）、达到血浆峰浓度所需的时间（tmax）以及消除半衰期（t1/2）。这是一项随机、单盲、两周期、交叉研究，纳入了18名处于禁食状态的健康成年男性和女性受试者。在两个研究周期中的每个周期（间隔两周洗脱期），给予单剂量的试验药物或参比药物。给药后至120小时采集血样，分离血浆，采用液相色谱-串联质谱法测定阿奇霉素浓度。在本研究中，试验药物的阿奇霉素平均AUCt、AUCinf、Cmax和t1/2分别为4967.49 ng·h·mL⁻¹、5871.74 ng·h·mL⁻¹、412.14 ng/mL和51.32小时。参比药物的阿奇霉素平均AUCt、AUCinf、Cmax和t1/2分别为4276.75 ng·h·mL⁻¹、5578.12 ng·h·mL⁻¹、419.89 ng/mL和51.23小时。试验药物和参比药物的tmax中位数分别为3.0小时和2.0小时。阿奇霉素试验药物/参比药物的几何平均比值（90%置信区间），AUCt为101.56%（86.61-119.08%），AUCinf为101.27%（84.97-120.70%），Cmax为97.78%（84.50-113.16%）。基于本研究，得出结论：两种阿奇霉素片剂（试验药物和参比药物）在吸收速率和程度方面生物等效。
