利福平及异烟肼对家兔体内地西泮药代动力学的影响

EFFECTS OF RIFAMPIN AND ISONIAZID ON THE PHARMACOKINETICS OF DIAZEPAM IN RABBITS

摘要: 用HPLC测定方法,研究了家兔多次ig利福平(100mg·kg^-1·d^-1×4)及异烟肼(50mg·kg^-1×4)后,对iv地西泮的药代动力学。结果表明,给药后利福平组肝微粒体细胞色素P-450含量增加98.1%,使地西泮的T_1/2β由98.77±19.38min减少到40.08±17.75min;AUC由143.52±41.41mg·min·L^-1减少到79.10±11.46mg·min·L^-1;CL由22.41±8.12ml·min^-1·kg^-1增加到43.96±10.38ml·kg^-1·min^-1。异烟肼组则表现出相反的作用。而利福平与异烟肼合用组对P-450含量及地西泮的动力学均无显著影响。提示利福平诱导家兔肝药酶的作用可加速地西泮的体内代谢过程,异烟肼抑制肝药酶减低地西泮的代谢。

Abstract: The pharmacokinetics of diazepam(3 mg · kg^-1,iv) in rabbits was studied after pretreatment with rifampin(RFP,100mg · kg^-1·d^-1×4),isoniazid (INH,50 mg·kg^-1·d^-1×4 ) and RFP+INH.The results showed that RFP significantly increased cytochrome P-450 content (CL) was increased in the RFP group. In the INH group the T_1/2 and AUC of diazepam were significantly increased and the CL was sigifiacntly decreased. However, cytochrome P-450 content and the pharmacokinetic parameters of diazepam were not changed in the RFP+INH group.