盐酸索他洛尔的正常人体药代动力学及生物利用度的研究

EVALUATION OF BIOAVAILABILITY AND PHARMACOKINETICS OFSOTALOL IN HEALTH VOLUNTEERS

本文研究了１２名男性健康志愿者单剂口服国产和进口盐酸索他洛尔片剂１６０ｍｇ的药代动力学和相对生物利用度。按照随机、交叉试验设计，采集服药后０．５，１．０，１．５，２，３，４，６，８，１２，２４，３６，４８ｈ的血样本。ＨＰＬＣ方法测定索他洛尔的血药浓度。两种制剂的药－时曲线符合口服吸收有滞后时间的二房室模型及一级动力学吸收、消除过程。国产索他洛尔的主要药代动力学参数：Ｃｍａｘ１．４５±０．３６ｍｇ／ｌ，Ｔｐｅａｋ２．５±０．９８ｈ，Ｔ１／２β９．６７±１．６７ｈ，ＡＵＣ０－ｔ１４．９２±２．８５ｍｇ·ｈ·Ｌ－１。国产索他洛尔相对于进口制剂的生物利用度为９９．７±１７．８％，国产索他洛尔与进口制剂生物等效。

The pharmacokinetics and relative bioavailability of domestic sotalol tablets were studied in 12 healthy male volunteers. A single oral dose of 160 mg of domestic or imported sotalol (test and reference preparation) was given according to a randomized 2-way cross-over design, blood samples were withdrawn up to 48 hours post administration, and plasma concentrations of sotalol were assayed by a high performance liquid chromatography ( HPLC ) method. The concentration-time curves of two preparations fitted to a two-compartment model with first order absorption and elimination. The main pharmacokinetic parameters of the test preparation were as follows: Cmax 1.45 ±0.36 mg·L-1 , Tpeak 2.50±0.98 h, T1/2β 9.67±1.67 h, AUC0-t 14.92 ±2.85 mg·h·L-1. The pharmacokinetics and relative bioavailability data obtained in the study furnished definite proof of bioequivalence of both domestic and imported sotalol tablets.