Effect of rilpivirine on the pharmacokinetics of methadone in HIV-Infected Chinese patients

ABSTRACT

Background: The combination of rilpivirine with methadone may result in complex interactions secondary to the induction of oxidative metabolism by rilpivirine.

Research design and methods: TMC278IFD4007 was a single-center, prospective, open-label, multiple-dose study with 12 HIV-infected Chinese participants. The objective was to evaluate the potential effect of rilpivirine on the pharmacokinetics of methadone. The participants received a daily dose of 25 mg rilpivirine for 11 days with individualized methadone ranging from 25 to 100 mg. Pharmacokinetic studies of methadone were conducted on day 1 and 11. Opiate withdrawal symptoms were evaluated.

Results: A large inter-subject variability was noted in methadone pharmacokinetics. Rilpivirine increased methadone minimum and maximum plasma concentrations (Cmin; Cmax) and area under the plasma concentration-time curve versus methadone alone (least-square mean ratio; 90% confidence interval) by 5% (1.05; 0.46, 2.39), 5% (1.05; 0.73, 1.52), and 6% (0.75; 0.74, 1.50) as measured in S-methadone, and 5% (1.05; 0.50, 2.22), 5% (1.05; 0.74, 1.50), and 5% (1.05; 0.76, 1.46) as measured in R-methadone, respectively. No opioid withdrawal symptoms or methadone dose adjustments were reported. Co-administration was well tolerated without serious adverse effects or discontinuations.

Conclusion: Concomitant administration of rilpivirine was unlikely to have significant effects on the pharmacokinetics of methadone.

Trial registration: Chinese Clinical Trial Registry identifier: ChiCTR-TRC-14004908.

KEYWORDS:

• Methadone
• rilpivirine
• HIV
• drug interactions

Author contributions

SL, LH, CY, QM, and HL were involved in the conception and design. SL, LH, QM, and HL mainly contributed to analysis and interpretation of the data. SL, LH, CY, SZ, YZ, SH, RX and XL conducted the study. SL, QM, and HL drafted the paper, and all authors approved this submission. All authors agreed to be accountable for all aspects of the work.

Declaration of interest

QM received support in part from National Institute of Mental Health (K08MH98794). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Support was provided by the grant from Xian Janssen Pharmaceutical Ltd.