Pharmacokinetic interaction between HCV protease inhibitor boceprevir and methadone or buprenorphine in subjects on stable maintenance therapy.

Abstract

PURPOSE:

Intravenous opioid use is a common route of hepatitis C virus (HCV) infection; consequently, the prevalence of HCV is high among patients on methadone or buprenorphine/naloxone. The authors evaluated the pharmacokinetic interaction of boceprevir with methadone or buprenorphine/naloxone in patients on stable maintenance therapy.

METHODS:

This was a two-center, open-label, fixed-sequence study in 21 adult volunteers on stable maintenance therapy. Oral methadone (20-150 mg once daily) or sublingual buprenorphine/naloxone (8/2-24/6 mg once daily) was administered alone or in combination with boceprevir (800 mg every 8 h) on days 2-7. Pharmacokinetic sampling occurred before and up to 24 h after the dose on days 1 and 7.

RESULTS:

Coadministration of boceprevir reduced the area under the concentration-time curve during a dosing interval τ (AUC τ ) and maximum observed plasma (or serum) concentration (C max) of R-methadone (geometric mean ratios (GMRs) [90 % confidence intervals (CIs)], 0.85 [0.74, 0.96] and 0.90 [0.71, 1.13]) and S-methadone (GMRs [90 % CIs], 0.78 [0.66, 0.93] and 0.83 [0.64, 1.09]). Boceprevir increased the AUC τ and C max of buprenorphine (GMRs [90 % CIs], 1.19 [0.91, 1.58] and 1.18 [0.93, 1.50]) and naloxone (GMRs [90 % CIs], 1.33 [0.90, 1.93] and 1.09 [0.79, 1.51]). Boceprevir exposure upon methadone or buprenorphine/naloxone coadministration was not clinically different from historical controls and there was no evidence of opioid withdrawal or excess.

CONCLUSIONS:

There was no clinically meaningful impact of boceprevir on methadone or buprenorphine pharmacokinetics, suggesting that methadone/buprenorphine dose adjustments are not required upon coadministration with boceprevir. Individual patients may differ in their clinical experience and clinicians should maintain vigilance when coadministering these medications.

• Authors: Ellen G J Hulskotte, R Douglas Bruce, Hwa-Ping Feng, Lynn R Webster, Feng Xuan, Wen H Lin, Edward O'Mara, John A Wagner, Joan R Butterton
• Journal: European journal of clinical pharmacology (Eur J Clin Pharmacol) Vol. 71 Issue 3 Pg. 303-11 (Mar 2015) ISSN: 1432-1041 [Electronic] Germany
• PMID: 25666027 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Buprenorphine, Naloxone Drug Combination
• Protease Inhibitors
• Buprenorphine
• N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide
• Proline
• Methadone

Topics

• Adolescent
• Adult
• Aged
• Buprenorphine (adverse effects, blood, pharmacokinetics)
• Buprenorphine, Naloxone Drug Combination (adverse effects, blood, pharmacokinetics)
• Drug Interactions
• Female
• Humans
• Maintenance Chemotherapy
• Male
• Methadone (adverse effects, blood, pharmacokinetics)
• Middle Aged
• Opiate Substitution Treatment (adverse effects)
• Proline (adverse effects, analogs & derivatives, blood, pharmacokinetics)
• Protease Inhibitors (adverse effects, blood, pharmacokinetics)
• Young Adult