Pharmacokinetic and Pharmacodynamic Study of the Concomitant Administration of Methadone and TMC125 in HIV‐Negative Volunteers.
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Study Design
In an open‐label, add‐on, 1‐way interaction trial, 16 male HIV‐negative volunteers on stable methadone maintenance therapy received 100 mg etravirine bid for 14 days. Plasma concentrations and pharmacokinetic parameters of R‐ and S‐methadone isomers were determined on days −1, 7, and 14 and of etravirine on days 7 and 14. Safety and tolerability were assessed
Study Results
The LSmeans ratios (90% confidence interval) for AUC24h, Cmax, and Cmin of the pharmacologically active R‐methadone were 1.08 (1.02–1.13), 1.03 (0.97–1.09), and 1.12 (1.05–1.19), respectively, on day 7 and 1.06 (0.99–1.13), 1.02 (0.96–1.09), and 1.10 (1.02–1.19), respectively, on day 14 compared with methadone alone. No withdrawal symptoms were observed; dose adjustment of methadone was not required.
Study Conclusions
The concomitant administration of etravirine and methadone was generally safe and well tolerated. Of note, the dosing of etravirine in this study is lower than that used clinically, and the significance of this finding is unknown. As dosed in the study, etravirine has no clinically relevant effect on the pharmacokinetics or pharmacodynamics of methadone. No dose adjustment for methadone is anticipated when coadministered with the concomitant use of etravirine.
References
Scholler-Gyure M, Brink W, Kakuda TN, Woodfall B, Smedt GD, Vanaken H, Hoetelmans RM. Pharmacokinetic and pharmacodynamic study of the concomitant administration of methadone and tmc125 in hiv‐negative volunteers. Journal Of Clinical Pharmacology. 2008; 3: 322-329.
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