Sarma G R, Immanuel C, Kailasam S, Narayana A S, Venkatesan P
Am Rev Respir Dis. 1986 Jun;133(6):1072-5. doi: 10.1164/arrd.1986.133.6.1072.
The effect of daily administration of rifampin on the direct conversion of isoniazid to isonicotinic acid and hydrazine by isoniazid hydrolase was investigated in 6 slow and 8 rapid acetylators of isoniazid. The proportion of isoniazid metabolized through this direct pathway during the first 6 h was estimated from the ratio of total isonicotinic acid formed to acetylisoniazid in urine after administration of isoniazid or acetylisoniazid. In slow acetylators, this proportion was approximately 3% when isoniazid alone was administered and approximately 6% during the maximal phase of induction caused by the daily administration of rifampin in addition to isoniazid (p less than 0.001); in rapid acetylators, the proportions were considerably less (less than 1 and 2.5%, respectively), suggesting that isoniazid hydrolase was induced by rifampin. The increased formation of hydrazine, a known hepatotoxic agent in animals, could explain the substantially higher frequency of the occurrence of hepatitis in slow than in rapid acetylators among tuberculous patients treated with daily rifampin and isoniazid.
在6名异烟肼慢乙酰化者和8名异烟肼快乙酰化者中，研究了每日服用利福平对异烟肼水解酶将异烟肼直接转化为异烟酸和肼的影响。通过服用异烟肼或乙酰异烟肼后尿液中形成的总异烟酸与乙酰异烟肼的比率，估算出前6小时内通过该直接途径代谢的异烟肼比例。在慢乙酰化者中，单独服用异烟肼时该比例约为3%，在除异烟肼外每日服用利福平引起的诱导最大阶段约为6%（p<0.001）；在快乙酰化者中，该比例明显较低（分别小于1%和2.5%），这表明利福平可诱导异烟肼水解酶。肼是一种已知的动物肝毒性剂，其生成增加可以解释在每日服用利福平和异烟肼治疗的结核病患者中，慢乙酰化者肝炎发生率明显高于快乙酰化者。
