Background and objectiveRifampin (INN, rifampicin) causes several drug interactions with coadministered antidiabetic drugs. Rosiglitazone is a novel thiazolidinedione antidiabetic drug, but little is known about the drug interaction between rifampin and rosiglitazone. Our objective was to investigate the effect of rifampin on the pharmacokinetics of rosiglitazone in humans.MethodIn an open‐label, randomized, 2‐way crossover study, 10 healthy Korean male subjects were treated once daily for 6 days with 600 mg rifampin or with placebo. On day 7, a single dose of 8 mg rosiglitazone was administered orally. Plasma rosiglitazone concentrations were measured.ResultsRifampin significantly decreased the mean area under the plasma concentration–time curve for rosiglitazone by 65% (2947.9 ng · h/mL versus 991.5 ng · h/mL, P < .001) and the mean elimination half‐life from 3.9 to 1.5 hours (P < .001). The peak plasma concentration of rosiglitazone was significantly decreased by rifampin (537.7 ng/mL versus 362.3 ng/mL, P < .01). The apparent oral clearance of rosiglitazone increased about 3‐fold after rifampin treatment (2.8 L/h versus 8.5 L/h, P < .001).ConclusionThis study showed that rifampin affected the disposition of rosiglitazone in humans, probably by the induction of cytochrome P450 (CYP) 2C8 and, to a lesser extent, CYP2C9. Therefore caution should be exercised during the coadministration of rifampin and rosiglitazone.Clinical Pharmacology & Therapeutics (2004) 75, 157–162; doi: 10.1016/j.clpt.2003.10.003