Effect of Rifampicin and Isoniazid Coadministration on the Metabolism and Pharmacokinetics of Isoniazid in Mice

Objective To study the pharmacokinetics changes of isoniazid and its metablites in rifampicin and isoniazid coadministrated mice.Methods Plasma samples were collected after 10 consecutive days of administration of isoniazid or rifampicin plus isoniazid once a day to mice.Isoniazid and its metablites-acetylhydrazine and hydrazine were determined by liquid chromatography/tandem mass spectrometry.Results Compared with isoniazid group,Ke,Cmax and AUC0-12h of acetylhydrazine increased significantly and t1/2 decreased significantly in rifampicin coadministrated group.AUC0-12h of hydrazine increased by 20% in rifampicin coadministrated group.Conclusion Acetylhydrazine and hydrazine,metabolites of isoniazid,increased significantly when isoniazid was coadministrated with rifampicin,suggesting that the increase of acetylhydrazine concentration plays a role in the hepatotoxicity of isoniazid and rifampicin coadministration.