The investigators concluded that GZR may be coadministered with methadone without dose adjustment. However, monitor the patient closely as PK parameters of GZR were variably affected when coadministered with methadone.
Grazoprevir vs opioid maintenance agents
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Study Design
In single-center, open-label, fixed sequence, and multiple dose study, 24 HCV-negative adults with ages 18-55 years on stable opiate maintenance therapy with methadone (20-150 mg daily) received grazoprevir (GZR; formerly known as MK-5172) 200 mg once daily for 10 days.
Study Results
Coadministration of GZR (200 mg daily) for 10 days did not significantly impact the pharmacokinetics (PK) of R-methadone (active enantiomer). Geometric mean ratios (GMRs; GZR +methadone / methadone) [90% CIs] of AUC and Cmax for R-methadone were 1.09 [1.02, 1.17] and 1.03 [0.96, 1.11], respectively. Coadministration of GZR (200 mg daily) for 10 days resulted in a slight increase of S-methadone (inactive enantiomer) exposure. GMRs (GZR +methadone / methadone) [90% CIs] of AUC and Cmax for S-methadone were 1.23 [1.12, 1.36] and 1.15 [1.07, 1.25], respectively. Coadministration with methadone modestly decreased GZR AUC by 15% and Cmax by 34%, but [90% CI] were wide; [0.47, 1.53] for AUC and [0.30, 1.45] for Cmax.No symptoms of opiate toxicity or withdrawal were noted.
References
Fraser IP, W Yeh, C Reitmann, et al. Lack of pk interaction between the hcv protease inhibitor mk-5172 and methadone or buprenorphine/naloxone in subjects on opiate maintenance therapy [abstract o_16_pk]. 8th International Workshop On Clinical Pharmacology Of Hepatitis Therapy. Cambridge, USA. ; 2013.
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