Pharmacokinetic interactions between buprenorphine/naloxone and once-daily lopinavir/ritonavir.
BACKGROUND
This study was conducted to examine the pharmacokinetic interactions between buprenorphine/naloxone (BUP/NLX) and lopinavir/ritonavir (LPV/r) in HIV-seronegative subjects chronically maintained on BUP/NLX.


METHODS
This study was an open labeled pharmacokinetic study in twelve HIV-seronegative subjects stabilized on at least 3 weeks of BUP/NLX therapy. Subjects sequentially underwent baseline and steady-state pharmacokinetic evaluation of once-daily LPV/r (800/200 mg).


RESULTS
Compared to baseline values, BUP AUC0-24h (46.8 vs. 46.2 ng*hr/mL) and Cmax (6.54 vs. 5.88 ng/mL) did not differ significantly after achieving steady-state LPV/r. Similar analyses of norBUP, the primary metabolite of BUP, demonstrated no significant difference in norBUP AUC0-24 hours (73.7 vs. 52.7 ng x h/mL); however, Cmax (5.29 vs. 3.11 ng/mL) levels were statistically different (P < 0.05) after LPV/r administration. Naloxone concentrations were similarly unchanged for AUC0-24 hours (0.421 vs. 0.374 ng x hr/mL) and Cmax (0.186 vs. 0.186 ng/mL). Using standardized measures, no objective opioid withdrawal was observed. The AUC0-24 hours and Cmin of LPV in this study did not significantly differ from historical controls (159.6 vs. 171.3 microg x hr/mL) and (2.3 vs. 1.3 microg/mL).


CONCLUSIONS
The addition of LPV/r to stabilized patients receiving BUP/NLX did not affect buprenorphine pharmacokinetics but did increase the clearance of norbuprenorphine. Pharmacodynamic responses indicate that the altered norbuprenorphine clearance did not lead to opioid withdrawal. Buprenorphine/naloxone and LPV/r can be safely coadministered without need for dosage modification.
Bruce
Robert Douglas
RD
Department of Medicine, Yale University AIDS Program, New Haven, CT, USA. robert.bruce@yale.edu
Altice
Frederick L
FL
Moody
David E
DE
Morse
Gene D
GD
Andrews
Laurie
L
Lin
Shen-Nan
SN
Fang
Wenfang B
WB
Ma
Qing
Q
Friedland
Gerald H
GH
D000328:Adult; D000701:Analgesics, Opioid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002047:Buprenorphine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009270:Naloxone / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011744:Pyrimidinones / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019438:Ritonavir / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000701:Analgesics, Opioid; D019380:Anti-HIV Agents; D011744:Pyrimidinones; D061466:Lopinavir; D009270:Naloxone; D002047:Buprenorphine; D019438:Ritonavir