Alisporivir + Methadone = Unknown or no reaction

Study Design

Part I: In an open-label screening study, the effect of steady state alisporivir on the pharmacokinetics (PK) of R- (active) and S- methadone was evaluated after a single dose of methadone. 16 healthy subjects received a single 5 mg dose of methadone on Day 1. After 7-day washout period, subjects received alisporivir (ALV) 600mg twice daily for 7days, followed by coadministration of ALV 600mg + methadone 5mg single dose on Day 8.Part 2: In a randomized, placebo-controlled, double blind study, the effect of ALV on the steady-state PK of R- and S- methadone was evaluated. 22 opioid-dependent patients on stable methadone maintenance therapy (MMT; =150 mg daily) were randomized (2:1; 14 ALV vs 8 placebo) to receive ALV 600 mg BID or placebo for 7 days. Blood samples were collected for R- and S-methadone concentrations prior to and after dose administration.

Study Results

In healthy subjects, geometric mean ratios (GMRs; ALV+methadone/ methadone) [90% CIs] of AUC and Cmax for R-methadone were 1.12 [1.04, 1.22] and 0.88 [0.78, 0.99], respectively; GMRs (ALV+methadone/ methadone) [90% CIs] of AUC and Cmax for S-methadone were 1.03 [0.94, 1.13] and 0.85 [0.77, 0.95], respectively. In opioid-dependent patients on stable MMT, geometric mean ratios (GMRs; ALV+methadone/ methadone) [90% CIs] of AUC and Cmax for R-methadone were 1.071 [0.958, 1.196] and 1.001 [0.904, 1.109], respectively; GMRs (ALV+methadone/ methadone) [90% CIs] of AUC and Cmax for S-methadone were 1.014 [0.895, 1.150] and 1.002 [0.889, 1.129], respectively.

Study Conclusions

References

Kovacs SJ, J Ke, A Barve, et al. Effect of therapeutic doses of alisporivir on methadone pharmacokinetics in healthy subjects and patients on stable methadone maintenance therapy (mmt) [abstract 840]. 48th Annual Meeting Of The European Association For The Study Of The Liver (easl). Amsterdam. ; 2013.