Effect of rifampicin on the pharmacokinetics of itraconazole in normal volunteers and AIDS patients |
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Authors: | S Jaruratanasirikul S Sriwiriyajan |
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Institution: | (1) Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla 90112, Thailand Tel.: 66-74-212070-9; Fax: 66-74-212900, 212903, 212912, TH |
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Abstract: | 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 · 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 μg · h · 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 μg · h · 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.
Received: 2 September 1997/Accepted in revised form: 16 December 1997 |
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Keywords: | Itraconazole Rifampicin |
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