Pharmacokinetic interaction between itraconazole and rifampin in Yucatan miniature pigs.

The objective of this study was to examine the effects of rifampin on itraconazole pharmacokinetics, at steady state, in three Yucatan miniature pigs. Daily for 3 weeks, the pigs received 200 mg of itraconazole orally at the beginning of each meal, and for the following 2 weeks they received itraconazole orally combined with intravenous administration of rifampin at 10 mg/kg/day. Coadministration of rifampin resulted in an 18-fold decrease in the maximum concentration of itraconazole in serum, from 113.0 (standard deviation [SD] 17.2) to 6.2 (SD, 3.9) ng/ml and a 22-fold decrease in the area under the concentration-time curve, from 1,652.7 (SD, 297.7) to 75.6 (SD, 30.0) ng.h/ml. The active metabolite of itraconazole, hydroxyitraconazole, was undetectable. This study demonstrates that rifampin affects itraconazole kinetics considerably at steady state in this miniature-pig model, probably by inducing hepatic metabolism of itraconazole.