环丙沙星片在中国健康受试者空腹和餐后状态下药代动力学及生物等效性研究

Pharmacokinetics and bioequivalence evaluation of ciprofloxacin tablets in healthy Chinese subjects under fasting and fed conditions

目的:评价中国健康受试者在空腹和餐后状态下口服环丙沙星片的药代动力学特征,并比较两种制剂的生物等效性。方法:采用随机、开放、两周期、双交叉给药设计,分别在空腹和餐后状态下,健康受试者单剂量口服环丙沙星片受试制剂或参比制剂250 mg。采用液相色谱-质谱串联法测定人血浆中环丙沙星的浓度,通过Phoenix WinNonlin 8.0软件采用非房室模型计算药代动力学参数,并评价两种制剂的生物等效性。结果:26例健康受试者随机入组空腹试验并完成研究。受试者空腹口服环丙沙星片后受试制剂和参比制剂的主要药代动力学参数:C_(max)分别为(1626±433)ng/mL和(1597±474)ng/mL,T_(max)分别为0.88(0.50,2.50)h和1.00(0.75,3.00)h,AUC_(0-t)分别为(6662±1376)h·ng·mL^(-1)和(6686±1237)h·ng·mL^(-1),AUC_(0-∞)分别为(6883±1408)h·ng·mL^(-1)和(6898±1261)h·ng·mL^(-1),t_(1/2)分别为(5.34±0.59)h和(5.18±0.60)h。两制剂药代动力学参数C_(max)、AUC_(0-t)、AUC_(0-∞)的几何均值比的90%置信区间分别为:96.03%~111.01%、96.12%~102.22%、96.28%~102.33%。26例健康受试者随机入组餐后试验,1例受试者因不良事件提前退出试验,其余25例受试者完成研究。受试者餐后口服环丙沙星片后受试制剂和参比制剂的药代动力学参数:C_(max)分别为(1134±315)ng/mL和(1104±342)ng/mL,T_(max)分别为1.50(0.50,5.00)h和1.75(0.50,4.02)h,AUC_(0-t)分别为(5041±965)h·ng·mL^(-1)和(5045±961)h·ng·mL^(-1),AUC_(0-∞)分别为(5269±1007)h·ng·mL^(-1)和(5264±1035)h·ng·mL^(-1),t_(1/2)分别为(5.75±0.85)h和(5.51±0.74)h。两制剂药代动力学参数C_(max)、AUC_(0-t)、AUC_(0-∞)的几何均值比的90%置信区间分别为:94.06%~114.12%、96.09%~103.13%、96.33%~103.40%。结论:环丙沙星片受试制剂和参比制剂在中国健康受试者空腹和餐后服用状态下生物等效。

AIM:To evaluate the pharmacokinetic properties and bioequivalence of two ciprofloxacin tablets in healthy Chinese subjects under fasting and fed conditions.METHODS:This is a randomized,open-label,two-period crossover study.Subjects were randomized to receive a single oral dose of the ciprofloxacin test or reference formulations 250 mg under fasting and fed conditions.Human plasma concentrations were determined using a liquid chromatography tandem mass spectrometry method(LC-MS/MS).A non-compartmental method by Phoenix WinNonlin 8.0 software was used for calculating pharmacokinetic parameters and evaluating bioequivalence of the two formulations.RESULTS:A total of 26 healthy subjects were enrolled the study under fasting conditions and completed it.The pharmacokinetic parameter values of the test and reference formulation under fasting conditions were as follows:C_(max) were(1626±433)ng/mL,(1597±474)ng/mL,T_(max) were 0.88(0.50,2.50)h,1.00(0.75,3.00)h,AUC_(0-t) were(6662±1376)h·ng·mL^(-1),(6686±1237)h·ng·mL^(-1),AUC_(0-∞) were(6883±1408)h·ng·mL^(-1),(6898±1261)h·ng·mL^(-1),t_(1/2) were(5.34±0.59)h,(5.18±0.60)h.The 90%confidence intervals of the geometric least-squares mean ratios of the test to reference formulation were 96.03%-111.01%for C_(max),96.12%-102.22%for AUC_(0-t) and 96.28%-102.33%for AUC_(0-∞).A total of 26 healthy subjects were enrolled the study under fed conditions.Due to adverse events,one subjects withdrew from the study after the first period.25 subjects completed the whole study.The pharmacokinetic parameter values of the test and reference formulation under fed conditions were as follows:C_(max) were(1134±315)ng/mL,(1104±342)ng/mL,T_(max) were 1.50(0.50,5.00)h,1.75(0.50,4.02)h,AUC_(0-t) were(5041±965)h·ng·mL^(-1),(5045±961)h·ng·mL^(-1),AUC_(0-∞) were(5269±1007)h·ng·mL^(-1),(5264±1035)h·ng·mL^(-1),t_(1/2) were(5.75±0.85)h,(5.51±0.74)h.The 90%confidence intervals of the geometric least-squares mean ratios of the test to reference formulation were 94.06%-114.12%for C_(max),96.09%-103.13%for AUC_(0-t) and 96.33%-103.40%for AUC_(0-∞).CONCLUSION:The two ciprofloxacin tablets were bioequivalent under fasting and fed conditions.