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Abstract
1. The pharmacokinetics of the antimycobacterial agent rifabutin were studied in healthy volunteers, following single (450 mg) and repeated (450 mg once daily for 10 days) oral administration.
2. After repeated administration, induction of metabolism was indicated by lower AUC and Cmin values, compared to the corresponding theoretical values. The elimination half-life was unchanged after repeated administration.
3. Induction of presystemic extrahepatic metabolism, which seems to be important in the availability of rifabutin, should be mainly responsible for the decrease in the AUC observed, while induced systemic clearance (if any) should be of minor importance.
4. Induction of presystemic extrahepatic metabolism after repeated administration has also been reported for rifampicin, an antibiotic agent with hepatic enzyme-inducing properties, which has a structure similar to rifabutin but a different pharmacokinetic profile.
