利福平及异烟肼对家兔体内地西泮药代动力学的影响

• 作 者: 龙超峰 张远 楼雅卿
• 机 构: 北京医科大学基础医学院药理学系
• 出 处: 药学学报
• 发表日期: 1997年07期
• 关键词: 利福平 异烟肼 地西泮 药物代谢酶 微粒体 药代动力学

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Ｔ１／２β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

The effects of rifampicin (100 mg · kg-1 · d-1 × 4) and isoniazid (50 mg · kg-1 × 4) on rabbits were studied by HPLC. A generation of dynamics. The results showed that after administration of rifampicin group liver microsomal cytochrome P 450 content increased 98.1%, the diazepam T1 / 2β decreased from 98.77 ± 19.38min to 40.08 ± 17.77min ; AUC decreased from 14352 ± 4141mg · min · L-1 to 7910 ± 1146mg · min · L-1; CL increased from 2241 ± 812ml · min-1 · kg-1 To 4396 ± 1038ml · kg-1 · min-1. The isoniazid group showed the opposite effect. The combination of rifampicin and isoniazid on P  450 content and the kinetics of diazepam had no significant effect. Tip Rifampicin induced hepatic liver enzymes in rabbits can accelerate the metabolism of diazepam in vivo, isoniazid inhibition of liver enzymes reduce the metabolism of diazepam