利福平和吡嗪酰胺对大鼠体内异烟肼药代动力学的影响。

The effect of rifampicin and pyrazinamide on isoniazid pharmacokinetics in rats.

作者信息

Baldan Helen M, De Rosa Helene J, Brunetti Iguatemy L, Ximenes Valdecir F, Machado Rosângela G P

机构信息

Departamento de Princípios Ativos Naturais e Toxicologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP, Brasil.

出版信息

Biopharm Drug Dispos. 2007 Nov;28(8):409-13. doi: 10.1002/bdd.570.

DOI:10.1002/bdd.570

PMID:17828712

Abstract

Tuberculosis chemotherapy involves combination of the drugs isoniazid (INH), rifampicin (RMP) and pyrazinamide (PYR) for a 6-month period. The present work investigated the influence of RMP and PYR on the pharmacokinetic parameters of INH when groups of rats were pre-treated for 21 days with INH alone or in combination with RMP and/or PYR, in the following amounts per kg body weight: INH 100 mg; INH 100 mg+RMP 100 mg; INH 100 mg+PYR 350 mg; INH 100 mg+PYR 350 mg+RMP 100 mg. It was found that the co-administration of PYR caused an increase in the INH distribution volume (V(d)/F), half-life of elimination (t(1/2beta)) and clearance (Cl(T)/F), and a decrease in the area under curve 0 to 24 h (AUC). Co-administration of RMP caused an increase in the Cl(T)/F and a decrease in the AUC. The combination INH+PYR+RMP caused an increase in the Cl(T)/F and a decrease in the AUC. These significant pharmacokinetic interactions between the tuberculostatic drugs might be related to differences in the therapeutic and toxic effects.

摘要

结核病化疗需要将异烟肼（INH）、利福平（RMP）和吡嗪酰胺（PYR）联合使用6个月。本研究调查了单独使用INH或与RMP和/或PYR联合使用（每千克体重用量如下：INH 100毫克；INH 100毫克+RMP 100毫克；INH 100毫克+PYR 350毫克；INH 100毫克+PYR 350毫克+RMP 100毫克）预处理大鼠21天后，RMP和PYR对INH药代动力学参数的影响。结果发现，联合使用PYR会导致INH分布容积（V(d)/F）、消除半衰期（t(1/2β)）和清除率（Cl(T)/F）增加，0至24小时曲线下面积（AUC）减少。联合使用RMP会导致Cl(T)/F增加，AUC减少。INH+PYR+RMP联合使用会导致Cl(T)/F增加，AUC减少。这些抗结核药物之间显著的药代动力学相互作用可能与治疗效果和毒性作用的差异有关。