Translational Development and Clinical Pharmacology, Summit, NJ, USA.
Non-Clinical Development, Celgene Corporation, Summit, NJ, USA.
Clin Pharmacol Drug Dev. 2019 Apr;8(3):346-354. doi: 10.1002/cpdd.470. Epub 2018 May 10.
Pomalidomide is an immunomodulatory drug and the dosage of 4 mg per day taken orally on days 1-21 of repeated 28-day cycles has been approved in the European Union and United States to treat patients with relapsed/refractory multiple myeloma. Because pomalidomide is extensively metabolized prior to excretion, a total of 32 subjects (8 healthy subjects in group 1; 8 subjects with severe hepatic impairment in group 2; 8 subjects with moderate hepatic impairment in group 3; and 8 subjects with mild hepatic impairment in group 4) were enrolled in a multicenter, open-label, single-dose study to assess the impact of hepatic impairment on pomalidomide exposure. Following administration of a single oral dose of 4-mg pomalidomide, the geometric mean ratios of pomalidomide total plasma exposures (AUC) were 171.5%, 157.5%, and 151.2% and the geometric mean ratios of pomalidomide plasma peak exposures (C ) were 75.8%, 94.8%, and 94.2% for subjects with severe, moderate, or mild hepatic impairment, respectively, versus healthy subjects. Pomalidomide administered as a single oral 4-mg dose was safe and well tolerated by healthy subjects and subjects with severe, moderate, or mild hepatic impairment. Based on the pharmacokinetic results from this study, the pomalidomide prescribing information approved by the US Food and Drug Administration recommends for patients with mild or moderate hepatic impairment (Child-Pugh classes A or B), a 3-mg starting daily dose (25% dose reduction) and for patients with severe hepatic impairment (Child-Pugh class C), a 2-mg starting daily dose (50% dose reduction).
泊马度胺是一种免疫调节药物，在欧盟和美国，其每天口服 4 毫克、重复 28 天周期的方案已被批准用于治疗复发性/难治性多发性骨髓瘤患者。由于泊马度胺在排泄前广泛代谢，因此共纳入 32 名受试者（1 组 8 名健康受试者；2 组 8 名严重肝损伤受试者；3 组 8 名中度肝损伤受试者；4 组 8 名轻度肝损伤受试者）进行了一项多中心、开放标签、单次剂量研究，以评估肝损伤对泊马度胺暴露的影响。在给予 4 毫克单口服剂量泊马度胺后，与健康受试者相比，严重、中度或轻度肝损伤受试者的泊马度胺总血浆暴露（AUC）几何均数比值分别为 171.5%、157.5%和 151.2%，泊马度胺血浆峰暴露（C ）几何均数比值分别为 75.8%、94.8%和 94.2%。单次口服 4 毫克泊马度胺治疗在健康受试者和严重、中度或轻度肝损伤受试者中安全且耐受良好。基于该研究的药代动力学结果，美国食品和药物管理局批准的泊马度胺处方信息建议轻度或中度肝损伤（Child-Pugh 分级 A 或 B）患者的起始日剂量为 3 毫克（剂量减少 25%），严重肝损伤（Child-Pugh 分级 C）患者的起始日剂量为 2 毫克（剂量减少 50%）。
