Objective: To investigate the effects of rifampicin on the pharmacokinetics of itraconazole in humans.
Methods: Our study was conducted with six healthy normal volunteers and three AIDS patients. All subjects received a 200 mg single dose of oral itraconazole on day 1 and day 15 and 600 mg of oral rifampicin once daily from day 2 to day 15. Itraconazole pharmacokinetics studies were carried out on day 1 (phase 1) and day 15 (phase 2). The limit of detection for itraconazole concentration was 16 ng x ml(-1).
Results: Concentrations itraconazole were higher when it was administered alone than when it was administered with rifampicin. Coadministration of rifampicin resulted in undetectable levels of itraconazole in all subjects except one normal volunteer. The mean AUC0-24 was 3.28 vs 0.39 microg x h x ml(-1) in phase 1 and 2, respectively, in healthy normal volunteers. Therefore, the estimated minimum decrease of the mean AUC0-24 of itraconazole in phase 2 was approximately 88% compared with phase 1. The mean AUC0-24 was 1.07 vs 0.38 microg x h x ml(-1) in phase 1 and 2, respectively, in AIDS patients. Therefore, the estimated minimum decrease of the mean AUC0-24 of itraconazole in phase 2 was approximately 64% compared with phase 1.
Conclusion: Rifampicin has a very strong inducing effect on the metabolism of itraconazole, so that these two drugs should not be administered concomitantly.