Methadone and buprenorphine pharmacokinetics and pharmacodynamics when coadministered with fostemsavir to opioid‐dependent, human immunodeficiency virus seronegative participants

Article date: August 2019

By: Katy Moore, Mindy Magee, Heather Sevinsky, Ming Chang, Susan Lubin, Elsa Myers, Peter Ackerman, Cyril Llamoso in Volume 85, Issue 8, pages 1771-1780


Regional human immunodeficiency virus (HIV) prevalence rates are high in people with history of injection drug use, including those managed with maintenance opioids. Fostemsavir (FTR) is an oral prodrug of temsavir, a first‐in‐class attachment inhibitor that binds HIV‐1 gp120, preventing initial HIV attachment and entry into host immune cells. Here we determine the impact of FTR on the pharmacokinetics of opioids methadone (MET: R‐, S‐ and total) or buprenorphine and norbuprenorphine (BUP and norBUP) when coadministered.


Study 206216 (NCT02666001) was a Phase I, open‐label study, assessing the effect of FTR 600 mg (extended‐release formulation) twice daily on pharmacokinetics of MET or BUP and norBUP, in non‐HIV‐infected participants on stable maintenance therapy with MET (40–120 mg; n = 16) or BUP plus naloxone (8–24 mg plus 2–6 mg; n = 16); pharmacodynamic response was assessed using standard opioid rating scales.


Following coadministration with FTR, dose‐normalized MET (R‐, S‐ and total) exposures (maximum concentration in plasma, area under the plasma concentration–time curve over the dosing interval and concentration in plasma at 24 hours) increased 9–15% and BUP and norBUP exposures increased 24–39%. The 90% confidence interval ranges for MET (1.01–1.21) and BUP and norBUP (1.03–1.69) were within respective no‐effect ranges (0.7–1.43 and 0.5–2.0). Opioid pharmacodynamic scores were similar with and without MET/BUP with no symptoms of withdrawal/overdose; no new safety signal for FTR when combined with a stable opioid regimen.


FTR did not impact MET and had no clinically significant impact on BUP pharmacokinetics. Standardized assessments of opioid pharmacodynamics were unchanged throughout FTR administration with MET or BUP. FTR can be administered with MET or BUP without dose adjustment.

DOI: 10.1111/bcp.13964

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