Perucca E, Grimaldi R, Frigo G M, Sardi A, Mönig H, Ohnhaus E E
Department of Internal Medicine and Therapeutics, University of Pavia, Italy.
Eur J Clin Pharmacol. 1988;34(6):595-9. doi: 10.1007/BF00615223.
The comparative enzyme inducing effects of rifabutin and the chemically related drug rifampicin have been investigated in 8 normal subjects. Rifampicin 600 mg daily for 7 days caused considerable shortening of the antipyrine half-life and a marked increase in antipyrine clearance, associated with an increased rate of conversion to norantipyrine and, to a lesser extent, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine. The urinary excretion of 6-beta-hydroxycortisol was also markedly increased, while plasma GGT activity showed only a slight albeit statistically significant elevation. In the same subjects, rifabutin in the proposed therapeutic dosage (300 mg daily) for 7 days also enhanced the metabolic elimination of antipyrine, with preferential stimulation of the demethylation pathway, and increased the excretion of 6-beta-hydroxycortisol, but the magnitude of the effects was significantly less than after rifampicin. No significant change in plasma GGT was seen. The results indicate that, contrary to the findings in animals, rifabutin does have enzyme inducing properties in man, although at the dosages assessed they were considerably less than those of rifampicin.
已在8名正常受试者中研究了利福布汀与化学相关药物利福平的比较酶诱导作用。每天服用600 mg利福平，连续7天，可使安替比林半衰期显著缩短，安替比林清除率显著增加，同时转化为去甲安替比林的速率加快，在较小程度上转化为4-羟基安替比林和3-羟甲基安替比林的速率也加快。6-β-羟基皮质醇的尿排泄也显著增加，而血浆γ-谷氨酰转移酶（GGT）活性仅略有升高，尽管具有统计学意义。在同一受试者中，以建议的治疗剂量（每天300 mg）服用利福布汀7天，也增强了安替比林的代谢消除，优先刺激去甲基化途径，并增加了6-β-羟基皮质醇的排泄，但作用程度明显小于服用利福平后。血浆GGT未见显著变化。结果表明，与在动物中的发现相反，利福布汀在人体中确实具有酶诱导特性，尽管在所评估的剂量下，其酶诱导特性远低于利福平。
