盐酸托烷司琼胶囊的人体药动学和生物等效性研究

 目的研究盐酸托烷司琼胶囊的人体药动学和相对生物利用度并求证国产盐酸托烷司琼胶囊的生物等效性。方法18名男性健康志愿者随机交叉给药,分别单剂量口服国产的盐酸托烷司琼胶囊(受试试剂)及进口的盐酸托烷司琼胶囊(参比试剂),采用HPLC-二极管阵列紫外法测定受试者血浆中的盐酸托烷司琼的浓度,计算两者药动学参数及相对生物利用度,并求证两制剂的生物等效性。结果口服两制剂后的主要药动学参数:t_max分别为(1.86±0.43)和(2.03±0.52)h,ρ_max分别为(11.73±3.05)和(11.25±3.30)μg·L^-1,AUC_(0～24)分别为(111.89±39.86)和(113.61±40.34)μg·h·L^-1;t_1/2(kα)分别为(0.79±0.29)和(0.82±0.25)h;t_1/2(ke)分别为(5.08±1.92)和(5.48±2.08)h;Ke分别为(0.16±0.06)和(0.14±0.05)h^-1。国产盐酸托烷司琼对于进口盐酸托烷司琼的平均相对生物利用度F-AUC_0～24为(98.55±10.37)%,F-AUC_0-inf为(99.77±18.66)%。两种胶囊剂的ρ_max,AUC_(0-24),AUC_0-inf经对数转换后3P97程序方差分析和双单侧t检验(α=0.05),结果表明,两种制剂在给药周期及处方间均无显著性差异(P>0.05),两制剂间生物等效。结论国产盐酸托烷司琼和进口盐酸托烷司琼生物等效。

Pharmacokinetic and Bioequivalence Study of Tropisetron Chlorate Capsule in Human

OBJECTIVE To study the pharmacokinetics and relative bioavailability of tropisetron hydrochloride capsules in healthy volunteers and to evaluate the bioequivalence.METHODS A single dose of 10 mg reference and test tropisetron capsules was given to 18 healthy volunteers in a randomized 2-way cross-over study.The concentrations of tropisetron hydrochloride in plasma were determined by RP-HPLC-UV.RESULTS The main pharmacokinetic parameters of two formulations,reference and test drug were as follows:t_max(1.86±0.43) and(2.03±0.52)h,ρ_max(11.73±3.05) and(11.25±3.30) μg·L^-1,AUC_0～24(111.89±39.86) and(113.61±40.34) μg·h·L^-1;AUC_0-inf(139.71±60.35) and(142.22±57.34) μg·h·L^-1,t_1/2(kα)(0.79±0.29) and(0.82±0.25)h;t_1/2(ke)(5.08±1.92) and((5.48±2.08)) h,Ke(0.16±0.06) and(0.14±0.05) h^-1,respectively.The relative bioavailability of AUC_0～24 and AUC_0-inf were(98.55±10.37)% and(99.77±18.66)%.Using 3P97 program,the results of variance and two one-sided test statistical analysis for Lnρ_max,LnAUC_0～24 and LnAUC_0-inf showed that two formulations were bioequivalent.CONCLUSION The reference and test tropisetron capsules are bioequivalent.