Effect of rifampicin pretreatment on the oral bioavailability of domperidone in healthy human volunteers.

Abstract

Increased exsorption of domperidone was observed from different parts of the small intestine of the rat after pretreatment with rifampicin by the everted sac method. Based on the in vitro studies the effect of rifampicin pretreatment on the pharmacokinetics of domperidone was investigated in eight healthy male volunteers. After an overnight fast, 20 mg domperidone was administered to the volunteers, either alone or after 6 days pretreatment with a once daily dose of 600 mg rifampicin. Serum concentrations of domperidone were estimated by reverse phase HPLC. Pharmacokinetic parameters were determined based on non-compartmental model analysis using the computer program kinetica. Rifampicin pretreatment decreased Cmax, AUCo-∞, AUMC, MRT and t1/2 by 25.11%, 37.76%, 64.97%, 43.71% and 44.48%, respectively. 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 domperidone is co-administered with rifampicin in chronic treatment conditions, such as tuberculosis, leprosy and other infections of joints, bones, etc.