Moltó José, Bailón Lucía, Pérez-Mañá Clara, Papaseit Ester, Miranda Cristina, Martín Soraya, Mothe Beatriz, Farré Magí
Department of Infectious Diseases, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
Fundació Lluita contra la Sida, Badalona, Spain.
J Antimicrob Chemother. 2021 Dec 24;77(1):181-184. doi: 10.1093/jac/dkab359.
Potential 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.
Fifteen healthy adults were enrolled in this randomized, double-blind, placebo-controlled, two-arm, crossover clinical trial. Participants underwent two 5 day treatment periods with at least a 1 week washout period between them. In each treatment period, participants received cobicistat (150 mg q24h orally) or matched placebo. On day 5 of each treatment period, participants were given a single oral dose of GHB (25 mg/kg). Plasma concentrations of GHB, subjective effects, blood pressure, heart rate and oxygen saturation were monitored for 5 h 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).
Ten 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.
Neither pharmacokinetic nor pharmacodynamic drug-drug interactions between cobicistat and GHB were identified in this study.
近年来，在从事性接触化学物质使用的艾滋病毒感染者中，出现了γ-羟基丁酸（GHB）过量的病例，有人提出细胞色素P450 3A4（CYP3A4）抑制剂与GHB之间的潜在相互作用可能是一个解释。我们的目的是评估考比司他对GHB药代动力学的影响。
15名健康成年人参加了这项随机、双盲、安慰剂对照、双臂交叉临床试验。参与者经历了两个为期5天的治疗期，其间至少有1周的洗脱期。在每个治疗期，参与者接受考比司他（150毫克，口服，每24小时一次）或匹配的安慰剂。在每个治疗期的第5天，给参与者口服单次剂量的GHB（25毫克/千克）。给药后5小时监测GHB的血浆浓度、主观效应、血压、心率和血氧饱和度。通过非房室分析计算每个参与者在每个研究期的GHB药代动力学和药效学参数，并使用线性混合效应模型进行比较。该研究已在https://www.clinicaltrialsregister.eu（欧盟临床试验编号2019-002122-71）和https://clinicaltrials.gov（NCT04322214）注册。
10名参与者完成了两个研究期。研究期间未发生需要受试者退出或医疗干预的药物相关不良事件。与安慰剂相比，考比司他与GHB联合给药后，GHB的主要药代动力学参数均未发生实质性变化。同样，单独使用GHB或与考比司他联合使用时，在主观或生理效应方面未观察到差异。
本研究未发现考比司他与GHB之间存在药代动力学或药效学药物相互作用。
