@article {3076,
	title = {Pharmacokinetic interactions between buprenorphine/naloxone and tipranavir/ritonavir in HIV-negative subjects chronically receiving buprenorphine/naloxone.},
	journal = {Drug and alcohol dependence},
	volume = {105},
	year = {2009},
	month = {2009 Dec 1},
	pages = {234-9},
	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.},
	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},
	issn = {1879-0046},
	doi = {10.1007/s10461-009-9532-3},
	author = {Bruce, R Douglas and Altice, Frederick L and Moody, David E and Lin, Shen-Nan and Fang, Wenfang B and Sabo, John P and Wruck, Jan M and Piliero, Peter J and Conner, Carolyn and Andrews, Laurie and Friedland, Gerald H}
}
