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Zhongguo yao li xue bao = Acta pharmacologica Sinica

Effects of rifampicin on pharmacokinetics of isoniazid and its metabolite acetylhydrazine in rats.


PMID 1302435

Abstract

After i.v. and i.p. injections of isoniazid (Iso) 40 mg.kg-1 to male Wistar rats, the plasma levels of Iso, acetylisoniazid (AcIso), and acetylhydrazine (AcHz) were determined by spectrophotometric method and gas chromatography. The results suggested that the pharmacokinetic behavior of Iso in rats belonged to a 2-compartment model. The plasma levels of AcHz in rifampicin (Rif 30 mg.kg-1)-pretreated rats were lowered vs the control (P < 0.05 or < 0.01). The T1/2 of AcHz was shortened by Rif (control group 3.3 h, Rif-pretreated group 1.4 h) after i.v. injection of AcHz 10 mg.kg-1 to rats and the results showed that AcHz was converted to its active metabolites quickly by increasing the oxidative elimination rate of AcHz, which is related to the higher incidence of liver necrosis caused by Iso and Rif in combination.

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