齐留通片在健康人体内的药动学

Pharmacokinetics of zileuton tables in healthy volunteers

目的研究齐留通在中国健康人体内单次和多次给药的药动学。方法12名健康志愿者,单次口服齐留通片0.6g或多次口服齐留通片0.6g·次^(-1),每曰4次,连续5d,在设计的时间点取静脉血。采用HPLC-UV法测定血药浓度,研究齐留通的药动学。结果单次口服齐留通片0.6g,平均血药浓度-时间变化规律符合单室模型,主要药动学参数如下:c_(max)为(6.6±s 2.0)mg·L^(-1);t_(max)为(1.9±0.3)h;t_(1/2)为(3.5±1.8)h;AUC_(0-6)为(19±6)mg·h·L^(-1),AUC_(0～12)为(25±8)mg·h·L^(-1);AUC_(0-∞)为(27±10)mg·h·L^(-1);CL/F为(26±8),L·h^(-1)。除t_(1/2)和t_(max)外,其余主要药动学参数在性别间有显著差异(P<0.05)。连续口服齐留通0.6g达到稳态后,主要药动学参数如下:c_(max)^(ss)为(7.4±1.6)mg·L^(-1);c_(min)^(ss)为(2.2±1.0)mg·L^(-1);c_(av)^(ss)为(3.5±1.0)mg·L^(-1);t_(max)^(ss)为(1.2±0.3)h;AUC_(0-6)^(ss)为(21±6)mg·h·L^(-1);AUC_(0-12)^(ss)为(26±8)mg·h·L^(-1);AUC_(0-x)^(ss)为(28±10)mg·h·L^(-1);t_(1/2)为(3.1±1.1)h;DF为(1.5±0.4)。连续给药5d,c_(max)、AUC、t_(1/2)等无明显增加(P>0.05),性别间除t_(max)^(ss)、t_(1/2)和DF外,主要药动学参数有显著差异(P<0.05),女性明显高于男性。结论齐留通片在人体内吸收迅速,分布广泛。中国健康志愿者体内的药动学参数在性别间有明显差异,多次给药后体内无明显蓄积现象。

AIM To evaluate the pharmacokinetics of zileuton in Chinese healthy volunteers. METHODS The plasma samples of 12 healthy volunteers （6 females and 6 males） were collected at the designed time points after a single （0.6 g） dose or multi-doses （0.6 g, 4 times a day, for 5 d） of zileuton tablets, and then pharmacokinetics were studied by HPLC-UV method. RESULTS After a single dose of zileuton, the concentrations-time curves were in accordance with one compartment model with first-order absorption and elimination. The main pharmacokinetic parameters were as follows： cmax, was （6.6 ± s 2.0） mg·L^-1; tmax, was （1.9 ± 0.3） h; t1/2 was （3.5 ± 1.8） h; AUC0-6 was （19± 6） mg·h·L^-1, AUC0-12was （25 ± 8） mg·h·L^-1; AUC0-∞ was （27 ± 10） mg· h· L^-1; CL/F was （26 ± 8） L· h^-1. Except tmax, and t1/2, the main pharmacokinetic parameters of zileuton showed significant difference between male and female （P 〈 0.05） . Parameters of multidose zileuton were as follows： cmax^ss was （7.4± 1.6） mg·L^-1, cmin^ss was （2.2± 1.0） mg·L^-1, cgv^ss was （3.5±1.0） mg· L^-1, tmax^ss was （1.2±0.3） h, AU0-6^ss was （21 ±6） mg·h·L^-1, AU0-12^ss was （26±8） mg·h·L^-1, AUC0-∞^ss was （28± 10） mg·h·L^-1, t1/2 was （3.1 ± 1.1） h, DFwas （1.5 ± 0.4）. Compared with single dose, cmax, AUC and t1/2 of multi-dose didn＇t increased obviously. Except tmax^ss, t1/2, and DF, the main pharmacokinetic parameters of zileuton in female were highter than those in male （P 〉 0.05）. CONCLUSION Zileuton can be absorbed rapidly and distributed widely in the body without accumulation in plasma after multiple-dose of administration. Significant gender differences exist in pharmacokinetic parameters in Chinese healthy volunteers.