The Journal of antimicrobial chemotherapy | 2021
Absence of drug-drug interactions between γ-hydroxybutyric acid (GHB) and cobicistat.
Abstract
OBJECTIVES\nPotential interactions between CYP3A4 inhibitors and γ-hydroxybutyric acid (GHB) have been suggested as a possible explanation for cases of GHB overdose in recent years among people living with HIV engaged in chemsex. Our objective was to assess the effect of cobicistat on the pharmacokinetics of GHB.\n\n\nMETHODS\nFifteen healthy adults were enrolled in this randomized, double-blind, placebo-controlled, two-arm, crossover clinical trial. Participants underwent two 5\u2009day treatment periods with at least a 1\u2009week washout period between them. In each treatment period, participants received cobicistat (150\u2009mg q24h orally) or matched placebo. On day 5 of each treatment period, participants were given a single oral dose of GHB (25\u2009mg/kg). Plasma concentrations of GHB, subjective effects, blood pressure, heart rate and oxygen saturation were monitored for 5\u2009h after dosing. GHB pharmacokinetic and pharmacodynamic parameters were calculated for each participant during each study period by non-compartmental analysis and were compared using linear mixed-effects models. The study was registered at https://www.clinicaltrialsregister.eu (Eudra-CT number 2019-002122-71) and at https://clinicaltrials.gov (NCT04322214).\n\n\nRESULTS\nTen participants completed the two study periods. No drug-related adverse events that necessitated subject withdrawal or medical intervention occurred during the study. Compared with placebo, none of the primary pharmacokinetic parameters of GHB was substantially changed by the administration of GHB with cobicistat. Similarly, no differences regarding subjective or physiological effects were observed when GHB was administered alone or with cobicistat.\n\n\nCONCLUSIONS\nNeither pharmacokinetic nor pharmacodynamic drug-drug interactions between cobicistat and GHB were identified in this study.