Title | Pharmacokinetic interactions between buprenorphine/naloxone and tipranavir/ritonavir in HIV-negative subjects chronically receiving buprenorphine/naloxone. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Bruce, Douglas R., Frederick L. Altice, David E. Moody, Shen-Nan Lin, Wenfang B. Fang, John P. Sabo, Jan M. Wruck, Peter J. Piliero, Carolyn Conner, Laurie Andrews, and Gerald H. Friedland |
Journal | Drug and alcohol dependence |
Volume | 105 |
Issue | 3 |
Pagination | 234-9 |
Date Published | 2009 Dec 1 |
ISSN | 1879-0046 |
Keywords | Adult, Anti-Retroviral Agents, Buprenorphine, Drug Interactions, Drug Therapy, Combination, Female, HIV Infections, HIV Seronegativity, Humans, Male, Middle Aged, Naloxone, Narcotic Antagonists, Opioid-Related Disorders, Pyridines, Pyrones, Ritonavir, Treatment Outcome |
Abstract | HIV-infected patients with opioid dependence often require opioid replacement therapy. Pharmacokinetic interactions between HIV therapy and opioid dependence treatment medications can occur. HIV-seronegative subjects stabilized on at least 3 weeks of buprenorphine/naloxone (BUP/NLX) therapy sequentially underwent baseline and steady-state pharmacokinetic evaluation of open-label, twice daily tipranavir 500 mg co-administered with ritonavir 200 mg (TPV/r). Twelve subjects were enrolled and 10 completed the study. Prior to starting TPV/r, the geometric mean BUP AUC(0-24h) and C(max) were 43.9 ng h/mL and 5.61 ng/mL, respectively. After achieving steady-state with TPV/r (> or = 7 days), these values were similar at 43.7 ng h/mL and 4.84 ng/mL, respectively. Similar analyses for norBUP, the primary metabolite of BUP, demonstrated a reduction in geometric mean for AUC(0-24h) [68.7-14.7 ng h/mL; ratio=0.21 (90% CI 0.19-0.25)] and C(max) [4.75-0.94 ng/mL; ratio=0.20 (90% CI 0.17-0.23)]. The last measurable NLX concentration (C(last)) in the concentration-time profile, never measured in previous BUP/NLX interaction studies with antiretroviral medications, was decreased by 20%. Despite these pharmacokinetic effects on BUP metabolites and NLX, no clinical opioid withdrawal symptoms were noted. TPV steady-state AUC(0-12h) and C(max) decreased 19% and 25%, respectively, and C(min) was relatively unchanged when compared to historical control subjects receiving TPV/r alone. No dosage modification of BUP/NLX is required when co-administered with TPV/r. Though mechanistically unclear, it is likely that decreased plasma RTV levels while on BUP/NLX contributed substantially to the decrease in TPV levels. BUP/NLX and TPV/r should therefore be used cautiously to avoid decreased efficacy of TPV in patients taking these agents concomitantly. |
DOI | 10.1007/s10461-009-9532-3 |
Alternate Journal | Drug Alcohol Depend |