利福平与异烟肼对苯妥英动力学的影响。
Influence of rifampicin and isoniazid on the kinetics of phenytoin.
作者信息
Kay L, Kampmann J P, Svendsen T L, Vergman B, Hansen J E, Skovsted L, Kristensen M
出版信息
Br J Clin Pharmacol. 1985 Oct;20(4):323-6. doi: 10.1111/j.1365-2125.1985.tb05071.x.
Clearance of phenytoin after i.v. injection of 100 mg was studied in six patients before and after 2 weeks daily treatment with 450 mg rifampicin, and in 14 patients with tuberculosis receiving standard treatment with 450 mg rifampicin, 300 mg isoniazid, and 1200 mg ethambutol daily. Acetylator status was measured by urinary acetylated sulphadimidine. Clearance of phenytoin in patients receiving only rifampicin increased from 46.7 ml min-1 +/- 20.6 ml min-1 to 97.8 ml min-1 +/- 33.4 ml min-1 (P less than 0.01), while clearance in patients on three drugs increased from 47.1 +/- 23.4 ml min-1 to 81.3 ml min-1 +/- 41.6 ml min-1 (P less than 0.01). No significant differences were observed between the six fast acetylators and the eight slow acetylators. Phenytoin kinetics were unchanged after further 3 months of combined treatment. Rifampicin is a strong inducer of the elimination of phenytoin. Combined treatment with isoniazid has no counter-acting effect in either fast or slow acetylators.
在6例患者静脉注射100 mg苯妥英后，研究了其在每日服用450 mg利福平2周前后的清除率，并在14例接受450 mg利福平、300 mg异烟肼和1200 mg乙胺丁醇标准治疗的结核病患者中进行了研究。通过尿中乙酰化磺胺嘧啶测定乙酰化状态。仅接受利福平治疗的患者中苯妥英的清除率从46.7 ml·min⁻¹±20.6 ml·min⁻¹增加到97.8 ml·min⁻¹±33.4 ml·min⁻¹（P<0.01），而接受三种药物治疗的患者清除率从47.1±23.4 ml·min⁻¹增加到81.3 ml·min⁻¹±41.6 ml·min⁻¹（P<0.01）。在6例快乙酰化者和8例慢乙酰化者之间未观察到显著差异。联合治疗3个月后苯妥英动力学未改变。利福平是苯妥英消除的强诱导剂。异烟肼联合治疗对快乙酰化者或慢乙酰化者均无拮抗作用。
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