Effects of rifampin and isoniazid on the pharmacokinetics of diazepam in rabbits
Long, C.F.; Zhang, Y.; Lou, Y.C.
Yao Xue Xue Bao 32(7): 481-484
1997
ISSN/ISBN: 0513-4870 PMID: 11596270 Document Number: 474299
The pharmacokinetics of diazepam (3 mg cntdot kg-1, iv) in rabbits was studied after pretreatment with rifampin (RFP, 100 mg cntdot kg-1 cntdot d-1 X 4), isoniazid (INH, 50 mg cntdot kg-1 cntdot d-1 X 4) and RFP + INH. The results showed that RFP significantly increased cytochrome P-450 content, but the T1/2 and AUC of diazepam were significantly decreased. The plasma clearance (CL) was increased in the RFP group. In the INH group the T1/2 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.