[Effects of rifampin and isoniazid on the pharmacokinetics of diazepam in rabbits].
The pharmacokinetics of diazepam (3 mg.kg-1, i.v.) in rabbits was studied after pretreatment with rifampin (RFP, 100 mg.kg-1.d-1 x 4), isoniazid (INH, 50 mg.kg-1.d-1 x 4) and RFP + INH. The results showed that RFP significantly increased cytochrome P-450 content, but the T 1/2 and AUC of diazepam were significantly decreased. The plasma clearance (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 significantly decreased. However, cytochrome P-450 content and the pharmacokinetic parameters of diazepam were not changed in the RFP + INH group. Our results indicate that RFP induces the activity of hepatic microsomal enzymes and increases the metabolism of diazepam, INH inhibits the activity of hepatic microsomal enzymes and decreases the metabolism of diazepam in rabbits.
Long
C F
CF
Department of Pharmacology, Beijing Medical University, Beijing 100083.
Zhang
Y
Y
Lou
Y C
YC
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003975:Diazepam / Q000493:pharmacokinetics*; D007538:Isoniazid / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D011817:Rabbits; D011897:Random Allocation; D012293:Rifampin / Q000494:pharmacology*
D003577:Cytochrome P-450 Enzyme System; D003975:Diazepam; D007538:Isoniazid; D012293:Rifampin