EFFECTS OF RIFAMPIN AND ISONIAZID ON THE PHARMACOKINETICS OF DIAZEPAM IN RABBITS

The pharmacokinetics of diazepam(3 mg · kg^-1,iv) in rabbits was studied after pretreatment with rifampin(RFP,100mg · kg^-1·d^-1×4),isoniazid (INH,50 mg·kg^-1·d^-1×4 ) and RFP+INH.The results showed that RFP significantly increased cytochrome P-450 content (CL) was increased in the RFP group. In the INH group the T_1/2 and AUC of diazepam were significantly increased and the CL was sigifiacntly decreased. However, cytochrome P-450 content and the pharmacokinetic parameters of diazepam were not changed in the RFP+INH group.