盐酸托烷司琼口腔崩解片在健康人体内的药动学及生物等效性

Pharmacokinetics and bioequivalence of tropisetron hydrochloride orally disintegrating tablets in healthy volunteers

目的建立测定人血浆中托烷司琼浓度的LC/MS/MS法,并用该法研究托烷司琼在健康人体内的药动学特征及其相对生物等效性。方法采用LC/MS/MS法,测定20名健康男性受试者口服含盐酸托烷司琼10 mg的受试制剂和参比制剂后,不同时刻血浆中托烷司琼的浓度,绘制药动学曲线并计算主要药动学参数。结果受试制剂和参比制剂中托烷司琼的主要药动学参数如下:tmax分别为(2.1±0.8)和(2.1±0.8)h;ρmax分别为(15.7±6.2)和(16.1±6.2)μg.L-1,t1/2分别为(9.9±5.0)和(9.4±5.0)h;用梯形法计算,AUC0-t分别为(213.2±162.7)和(210.1±159.2)μg.h.L-1,AUC0-∞分别为(231.0±190.4)和(231.2±190.9)μg.h.L-1。以AUC0-t计算,盐酸托烷司琼口腔崩解片中托烷司琼的相对生物利用度为(102.2±25.7)%。结论盐酸托烷司琼的两种制剂生物等效。

Objective To develop a sensitive and rapid LC/MS/MS method to determine the plasma concen- tration of tropisetron and study the pharmacokinetics and bioequivalence of tropisetron hydrochloride tablets in healthy volunteers. Methods Twenty healthy volunteers were given a single oral dosage of 10 mg tropisetron hydrochloride test and reference formulation. The concentrations of tropisetron in plasma were determined by LC/MS/MS. The plasma concentration-time curves were plotted and the main pharmacokinetic parameters were calculated. Results The main pharmacokinetic parameters of test and reference tablets in plas- ma were shown follows： tmax = （ 2. 1 ± 0. 8 ） and （ 2. 1 ± 0. 8 ） h, Pmax = （ 15. 7 ± 6. 2 ） and （ 16. 1 ± 6. 2）μg.L^-1,t1/2 = （9.9± 5.0）and（9.4 ± 5.0）h, AUC0-t = （213.2 ± 162.7）and （210. 1 ±159.2） μg.h.L^-1 ,AUC0-∞ = （231.0 ± 190. 4） and（231.2 ±190. 9）μg.h.L^-1. The relative bioavailability of tropisetron for test drug was（ 102. 2 ± 25.7 ） %. Conclusions The two kinds of tropisetron formulations are bio- equivalent in healthy volunteers.