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 minia ture 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 t hey received itraconazole orally combined with intravenous administrat ion of rifampin at 10 mg/kg/day, Coadministration of rifampin resulted in an Id-fold decrease in the maximum concentration of itraconazole i n 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 cu rve, from 1,652.7 (SD, 297.7) to 75.6 (SD, 30.0) ng . h/ml, The active metabolite of itraconazole, hydroxyitraconazole, was undetectable, Th is study demonstrates that rifampin affects itraconazole kinetics cons iderably at steady state in this miniature-pig model, probably by indu cing hepatic metabolism of itraconazole.