Tipranavir Ritonavir Induction of Buprenorphine Glucuronide Metabolism in HIV-Negative Subjects Chronically Receiving Buprenorphine Naloxone
Background: Previous reports on the pharmacokinetic of tipranavir (TPV) and buprenorphine (BUP)/ naloxone found that coadministration resulted in an 80% reduction in the area under the curve AUC of the primary BUP metabolite, norBUP, without any pharmacodynamic consequences. This study was conducted...
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Published in | The American journal of drug and alcohol abuse Vol. 37; no. 4; pp. 224 - 228 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Informa Healthcare
01.07.2011
Taylor & Francis Taylor & Francis Ltd |
Subjects | |
Online Access | Get full text |
ISSN | 0095-2990 1097-9891 1097-9891 |
DOI | 10.3109/00952990.2011.568081 |
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Summary: | Background: Previous reports on the pharmacokinetic of tipranavir (TPV) and buprenorphine (BUP)/ naloxone found that coadministration resulted in an 80% reduction in the area under the curve AUC of the primary BUP metabolite, norBUP, without any pharmacodynamic consequences. This study was conducted to characterize how tipranivir/ritonavir effects the glucuronide metabolites of BUP and may explain the reduction in the norBUP. Methods: HIV-seronegative subjects stabilized on at least 3 weeks of BUP/naloxone sequentially underwent baseline and steady-state pharmacokinetic evaluation of twice daily TPV 500 mg coadministered with ritonavir 200 mg (TPV/r). Results: Twelve subjects were enrolled and ten completed the study. The steady-state pharmacokinetics for BUP-3-glucuronide (BUP-3G) and norBUP-3-glucuronide (norBUP-3G) in the presence and absence of steady-state TPV/r were analyzed. The Cmax of BUP-3G was 8.78 ± 5.23 ng/mL without TPV/r and increased to 12.7 ± 11.7 after steady state of TPV/r was achieved. The AUC of BUP-3G was 31.1 ± 19.4 (ng/mL) (h) without TPV/r and increased to 58. 6 ± 49.5 after steady state of TPV/r was achieved (p = .0966). In contrast, steady-state norBUP-3G AUC0-24 h (p = .0216) and Cmax (p = .0088) were significantly decreased in the presence of steady-state TPV/r. Conclusions and Scientific Significance: This study further elucidates the effects of TPV/r on glucuronidation. The current evaluation of glucuronide metabolites of BUP and norBUP are suggestive of combined inhibition of Uridine diphosphate (UDP)-glucuronosyltransferase of the 1A family and cytochrome P450 3A4 that spares UGT2B7 leading to a shunting of BUP away from production of norBUP and toward BUP-3G as seen by a statistically significant increase in the AUC of BUP-3G. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Feature-1 content type line 23 |
ISSN: | 0095-2990 1097-9891 1097-9891 |
DOI: | 10.3109/00952990.2011.568081 |