Objective: To investigate the effect of pretreatment with rifampicin (rifampin) on the pharmacokinetics of tinidazole in healthy male volunteers. Design: Before/after non-blinded investigation conducted in healthy volunteers. Study Participants: 12 healthy male volunteers with a mean age of 24 ± 3y ears. Methods: After an overnight fast, tinidazole (500mg tablet) was administered to the volunteers, either alone or after a 5-day pretreatment period with a once-daily dose of rifampicin 600mg (2 × 300mg capsules) under direct observation. Serum concentrations of tinidazole were measured by reverse-phase high performance liquid chromatography. Pharmacokinetic parameters were determined from noncompartmental model analysis using the computer program RAMKIN. Results: A significant difference was observed in area under the concentrationtime curve (AUC) from 0 to 48 hours (254.77 ± 31.46 vs 208.07 ± 25.57 mg h/L, p < 0.0001), AUC from 0 to infinity (299.86 ± 47.70 vs 231.54 ± 36.19 mg h/L, p < 0.0001], elimination half-life (16.98 ± 2.73 vs 13.93 ± 3.45h, p < 0.0018) and clearance (27.62 ± 3.61 vs 35.82 ± 4.95 ml/h/kg, p < 0.0001) of tinidazole administered before and after rifampicin pretreatment. However, peak concentration (Cmax), time to reach Cmax and apparent volume of distribution were not affected significantly. Conclusions: Rifampicin pretreatment reduced the AUC of tinidazole by 23% and increased the clearance by 29%. This may be due to increased metabolism of tinidazole as a result of the induction of cytochrome P450 2C9 and 3A4 in liver/intestine and/or P-glycoprotein−mediated exsorption into the intestines. This interaction, however, may not have significant clinical relevance and does not warrant dosage adjustment because the extent of alteration in bioavailability of tinidazole is less than 25%.