齐留通片在健康人体内的药动学

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。

Pharmacokinetics of zileuton tables in healthy volunteers

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(0.6g,4 times a day,for 5d)of zileuton tablets,and then the 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:c_(max)was(6.6±s 2.0)mg·L~(-1);t_(max)was(1.9±0.3)h;t_(1/2)was(3.5±1.8)h;AUC_(0-6)was(19±6)mg·h·L~(-1),AUC_(0-12)was(25±8)mg·h·L~(-1);AUC_(0-∞) was(27±10)mg·h·L~(-1);CL/F was(26±8)L·h~(-1).Except t_(max)and t_(1/2),the main pharmacokinetic parameters of zileuton showed significant difference between male and female(P<0.05).Parameters of multi- dose zileuton were as follows:c_(max)~(ss)was(7.4±1.6)mg·L~(-1),c_(max)~(ss)was(2.2±1.0)mg·L~(-1),c_(av)~(ss)was(3.5±1.0)mg·L~(-1),t_(max)~(ss)was(1.2±0.3)h,AUC_(0-6)~(ss)was(21±6)mg·h·L~(-1),AUC_(0-12)~(ss)was(26±8)mg·h·L~(-1),AUC_(0-∞)~(ss)was(28±10)mg·h·L~(-1),t_(1/2)was(3.1±1.1)h,OF was(1.5±0.4).Compared with single dose,c_(max),AUC and t_(1/2)of multi-dose didn't increased obviously.Except t_(max)~(ss),t_(1/2),and DF,the main pharmacokinetic parameters of zileuton in female were bighter 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 pharrnaeokinetic parameters in Chinese healthy volunteers.