Pharmacokinetics and pharmacodynamics of a buprenorphine subcutaneous depot formulation (CAM2038) for once-weekly dosing in patients with opioid use disorder
Pharmacokinetics and pharmacodynamics of a buprenorphine subcutaneous depot formulation (CAM2038) for once-weekly dosing in patients with opioid use disorder
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DOI：
10.1016/j.jsat.2017.04.008
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发表时间：
2017-07-01
影响因子：
3.9
通讯作者：
Tiberg, Fredrik
中科院分区：
文献类型：
--
作者：
Haasen, Christian;Linden, Margareta;Tiberg, Fredrik
舌下丁丙诺啡对阿片类药物依赖治疗有效，但与误用、滥用和转移有关。目前的I/II期研究评估了一种新的丁丙诺啡皮下储存制剂，每周给药一次（CAM2038 q1w），用于接受阿片类药物使用障碍维持治疗的患者，每日舌下丁丙诺啡。方法：丁丙诺啡停药48小时后，患者在研究前每日舌下维持剂量的基础上接受单次CAM2038 q1w剂量。cam2038qlw剂量为7.5、15、22.5和30 mg，采用顺序剂量递增设计。进行以下评估：丁丙诺啡和去甲丁丙诺啡的药代动力学、药效学（使用主观和临床阿片戒断量表进行评估）和舌下丁丙诺啡救援药物的摄入时间。结果：单次给药CAM2038 q1w显示丁丙诺啡的剂量比例药效学（C-max和AUC(0-7d)），时间至Cmax h，表观终末半衰期为3-5天，支持每周一次给药。平均而言，患者的阿片类戒断症状从基线开始迅速而持久地减少，在给药CAM2038 q1w后至少7天内测量的SOWS和COWS值为零或非常低。首次使用丁丙诺啡抢救的中位时间为10天。由于CAM2038 q1w剂量的选择是基于患者的研究前维持剂量，因此在药效学上没有发现剂量依赖性。CAM2038 qw是安全的，总体耐受性良好。结论：评估了一种新型每周给药一次的丁丙诺啡皮下储存制剂的药代动力学和药效学，提示其在阿片类药物使用障碍患者的维持治疗中的效用。(C) 2017爱思唯尔公司版权所有。
Introduction: Sublingual buprenorphine is effective for opioid dependence treatment but associated with misuse, abuse, and diversion. The present Phase I/II study evaluated a novel buprenorphine subcutaneous depot formulation for once-weekly dosing (CAM2038 q1w) in patients receiving maintenance treatment for opioid use disorder with daily sublingual buprenorphine.Methods: After discontinuation of buprenorphine for 48 h, patients received a single CAM2038 q1w dose based on their pre-study daily sublingual maintenance dose. CAM2038 qlw doses of 7.5, 15, 22.5, and 30 mg were administered in a sequential dose-escalating design. The following assessments were performed: pharmacokinetics of buprenorphine and norbuprenorphine, pharmacodynamics (evaluated using the Subjective and Clinical Opiate Withdrawal Scales), and time to intake of rescue sublingual buprenorphine medication.Results: Single doses of CAM2038 q1w indicated dose-proportional buprenorphine pharmacoldnetics (C-max and AUC(0-7d)), with time to Cmax h and an apparent terminal half-life of 3-5 days, supporting once-weekly dosing. On average, patients showed a rapid and extended decrease in opiate-withdrawal symptoms from baseline, with zero or very low SOWS and COWS values measured at least up to 7 days after dosing of CAM2038 q1w. The median time to first use of rescue buprenorphine was 10 days. No dose dependence was seen in the pharmacodynamics, attributable to the selection of CAM2038 q1w doses based on patients' pre-study maintenance doses. CAM2038 qlw was safe and generally well tolerated.Conclusions: Pharmacokinetics and pharmacodynamics of a novel buprenorphine subcutaneous depot formulation for once-weekly dosing was evaluated, suggesting utility in maintenance treatment of patients with opioid use disorder. (C) 2017 Elsevier Inc. All rights reserved.