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Increased exsorption of ornidazole was observed from different parts of the small intestine of the rat after pretreated with rifampicin and sodium butyrate by the everted sac method. Based on the in vitro studies the effect of rifampicin pretreatment on the pharmacokinetics of ornidazole was investigated in eight healthy male volunteers. After an overnight fast, 500 mg ornidazole was administered to the volunteers, either alone or after 6 days pretreatment with a once daily dose of 600 mg rifampicin. Serum concentrations of ornidazole were estimated by reverse phase HPLC. Pharmacokinetic parameters were determined based on non-compartmental model analysis using the computer program Win Nonlin 1.1. Rifampicin preteatment resulted in a significant decrease in AUC, C(max) and t1/2, by 21.16%, 20.43% and 18.11%, respectively. Clearance was increased significantly by 32.14%. This may be due to increased induction of cytochrome P450 enzymes and/or increased expression of P-glycoprotein. This interaction may have clinical significance when ornidazole is co-administered with rifampicin in chronic treatment conditions, such as tuberculosis, leprosy and other infections of joints, bones, etc.

EFFECT OF RIFAMPICIN PRETREATMENT ON THE TRANSPORT ACROSS RAT INTESTINE AND ORAL PHARMACOKINETICS OF ORNIDAZOLE IN HEALTHY HUMAN VOLUNTEERS