Vaughan Adetola, Mensah Cassius K, Pennycuff Jenny, Venneman Sandy S, Risborough Victoria, Baker Dewleen G, Nowak Kayla J, Williams Rick L, Nolen Tracy L, Kosten Thomas R, Verrico Christopher D
J Addict Med. 2025 Aug 11. doi: 10.1097/ADM.0000000000001557.
PT150, a novel competitive glucocorticoid receptor antagonist, is hypothesized to be a potential treatment for alcohol use disorder, with safety studies as an important first step for medication development. We aimed to assess PT150 safety and tolerability, including impact on pharmacokinetics when administered concomitantly with ethanol in healthy participants.
This nonrandomized, single-site, drug-drug interaction study of PT150, coadministered with oral ethanol (alcohol beverage), was conducted at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, TX. Participants, each of whom received the same exposure sequence and served as their own control, were healthy, alcohol-experienced volunteers aged 21-64 years. Blood samples were obtained before and after 1.03 mL/kg ethanol exposure, before and after the fifth dose of PT150 (900 mg/d), and again before and after a sixth dose of PT150 (900 mg/d) administered with 1.03 mL/kg of ethanol. The primary pharmacokinetic outcomes included differences in peak plasma concentrations (Cmax), time to reach peak plasma concentrations (tmax), terminal elimination half-life (t1/2), and area under the concentration-time curve (AUC) of PT150 alone and in combination with ethanol.
There was no statistically significant evidence that coexposure to ethanol impacted PT150 pharmacokinetics, and no statistically significant evidence that coexposure to PT150 impacted ethanol pharmacokinetics. There were no clinically significant abnormal electrocardiograms or serious adverse events.
These data suggest that coadministration of PT150 and alcohol does not produce significant pharmacokinetic interactions, supporting the feasibility of evaluating PT150 in future clinical trials for alcohol use disorder.
PT150是一种新型竞争性糖皮质激素受体拮抗剂，据推测它可能是治疗酒精使用障碍的一种潜在药物，安全性研究是药物研发的重要第一步。我们旨在评估PT150的安全性和耐受性，包括在健康受试者中与乙醇同时给药时对药代动力学的影响。
这项关于PT150与口服乙醇（酒精饮料）联合使用的非随机、单中心药物相互作用研究在德克萨斯州休斯顿的迈克尔·E·德贝基退伍军人事务医疗中心进行。参与者均为21至64岁、有饮酒经历的健康志愿者，他们都接受相同的暴露顺序并作为自身对照。在摄入1.03 mL/kg乙醇前后、第五剂PT150（900 mg/d）给药前后以及第六剂PT150（900 mg/d）与1.03 mL/kg乙醇联合给药前后采集血样。主要药代动力学指标包括单独使用PT150以及PT150与乙醇联合使用时的血浆峰浓度（Cmax）、达峰时间（tmax）、末端消除半衰期（t1/2）和浓度-时间曲线下面积（AUC）的差异。
没有统计学上显著的证据表明同时接触乙醇会影响PT150的药代动力学，也没有统计学上显著的证据表明同时接触PT150会影响乙醇的药代动力学。没有具有临床意义的异常心电图或严重不良事件。
这些数据表明，PT150与酒精联合给药不会产生显著的药代动力学相互作用，这支持了在未来酒精使用障碍的临床试验中评估PT150的可行性。
