[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. The pits received daily during three weeks oral itraconazole at a dosage of 200 mg at the beginning of the meal, then during the next two weeks oral itraconazole combined with an intravenous administration of rifampin at a dosage of 10 mg/kg/day. The coadministration of rifampin resulted in a 18 fold decrease of the Cmax of itraconazole [from 113.0 (SD: 17.2) to 6.2 ng/ml (SD: 3.9)], and in a 22 fold decrease of the AUC [from 1652.7 (SD: 297.7) to 75.6 ng.h/ml (SD: 30.01)]. The active metabolite of itraconazole, hydroxyitraconazole, was undetectable. This study demonstrates that rifampin considerably affects itraconazole kinetics at steady-state in this model of micropig, probably by inducing the hepatic metabolism of itraconazole.