title: Pharmacokinetic interaction between itraconazole and rifampin in Yucatan miniature pigs.
abstract: 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.
authors.affiliation: Laboratoire de Pharmacocinétique de l'Institut de Bactériologie, Strasbourg, France.
authors.forename: G
authors.initials: G
authors.lastname: Kaltenbach
authors.forename: D
authors.initials: D
authors.lastname: Levêque
authors.forename: J D
authors.initials: JD
authors.lastname: Peter
authors.forename: J
authors.initials: J
authors.lastname: Salmon
authors.forename: H
authors.initials: H
authors.lastname: Elkhaili
authors.forename: A
authors.initials: A
authors.lastname: Cavalier
authors.forename: Y
authors.initials: Y
authors.lastname: Salmon
authors.forename: H
authors.initials: H
authors.lastname: Monteil
authors.forename: F
authors.initials: F
authors.lastname: Jehl
mesh_terms: D000818:Animals; D000904:Antibiotics, Antitubercular / Q000493:pharmacokinetics*; D000935:Antifungal Agents / Q000494:pharmacology*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D005260:Female; D007275:Injections, Intravenous; D017964:Itraconazole / Q000494:pharmacology*; D012293:Rifampin / Q000493:pharmacokinetics*; D013552:Swine; D013556:Swine, Miniature
chemical_list: D000904:Antibiotics, Antitubercular; D000935:Antifungal Agents; D017964:Itraconazole; D012293:Rifampin