A Single-Dose Study to Evaluate the Relative Bioavailability, Safety, and Tolerability of Monthly Extended-Release Buprenorphine at Alternative Injection Locations in Adult Participants with Opioid Use Disorder.

IF 2.9 3区医学 Q2 PHARMACOLOGY & PHARMACY Clinical Drug Investigation Pub Date : 2024-11-14 DOI:10.1007/s40261-024-01406-7

Celine M Laffont, Olga Lapeyra, Dipti Mangal, Robert Dobbins

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Abstract

Background and objectives: Buprenorphine extended-release monthly formulation (BUP-XR, SUBLOCADE^®) is approved for treatment of moderate-to-severe opioid use disorder (OUD) following subcutaneous injection in the abdomen. This open-label pharmacokinetic study assessed three alternative injection locations (upper arm, thigh, buttocks) to offer additional flexibility considering the chronic nature of the disease and patient preferences.

Methods: Following stabilization on 12/3 mg/day of sublingual buprenorphine/naloxone for ≥ 7 days, participants with moderate-to-severe OUD were randomized to receive a single 300-mg BUP-XR injection in the upper arm, thigh, buttocks, or abdomen (reference). Serial blood samples were taken to measure buprenorphine plasma concentrations over 28 days and assess buprenorphine relative bioavailability. Safety evaluations included treatment-emergent adverse events and assessments of injection site pain, tenderness, erythema, induration, and swelling.

Results: A total of 88 participants received a single subcutaneous injection of 300-mg BUP-XR in the upper arm (N = 21), thigh (N = 23), buttocks (N = 22), or abdomen (N = 22); 81/88 (92%) completed the study. Buprenorphine plasma exposure (area under the plasma concentration-time curve over 28 days) was comparable across injection site groups with mean buprenorphine plasma concentrations sustained at approximately 2 ng/mL (therapeutic target concentration) or above. Buprenorphine maximum plasma concentration (C_max) was approximately 39% and 52% higher after injection in the upper arm and thigh, respectively, versus the abdomen, while comparable between buttocks and abdomen. Higher C_max values were not associated with an increased incidence of adverse events. Safety and injection site tolerability were comparable across injection groups.

Conclusions: These pharmacokinetic and safety findings support BUP-XR injection into the upper arm, thigh, and buttocks.

Trial registration: Clinicaltrials.gov: NCT05704543.

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单剂量研究：评估阿片类药物使用失调症成年参与者在其他注射地点使用月度缓释丁丙诺啡的相对生物利用度、安全性和耐受性。

背景和目标：丁丙诺啡缓释月配方（BUP-XR，SUBLOCADE®）获准用于治疗中重度阿片类药物使用障碍（OUD），腹部皮下注射。这项开放标签药代动力学研究评估了三个替代注射位置（上臂、大腿、臀部），以提供更多灵活性，同时考虑到该疾病的慢性性质和患者的偏好：中度至重度 OUD 患者在稳定服用 12/3 毫克/天的丁丙诺啡/纳洛酮≥ 7 天后，被随机分配到上臂、大腿、臀部或腹部（参考）接受单次 300 毫克 BUP-XR 注射。在 28 天内连续采集血样以测量丁丙诺啡的血浆浓度，并评估丁丙诺啡的相对生物利用度。安全性评估包括治疗突发不良事件以及注射部位疼痛、触痛、红斑、压痕和肿胀评估：共有 88 名参与者在上臂（21 人）、大腿（23 人）、臀部（22 人）或腹部（22 人）单次皮下注射 300 毫克 BUP-XR；81/88（92%）人完成了研究。各注射部位组的丁丙诺啡血浆暴露量（28 天血浆浓度-时间曲线下面积）相当，平均丁丙诺啡血浆浓度维持在约 2 纳克/毫升（治疗目标浓度）或以上。上臂和大腿注射后的丁丙诺啡最大血浆浓度（Cmax）分别比腹部高出约 39% 和 52%，而臀部和腹部则相当。较高的 Cmax 值与不良事件发生率的增加无关。各注射组的安全性和注射部位耐受性相当：这些药代动力学和安全性研究结果支持在上臂、大腿和臀部注射 BUP-XR：试验注册：Clinicaltrials.gov：试验注册：Clinicaltrials.gov：NCT05704543。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Drug Investigation 医学-药学

CiteScore

5.90

自引率

3.10%

发文量

108

审稿时长

6-12 weeks

期刊介绍： Clinical Drug Investigation provides rapid publication of original research covering all phases of clinical drug development and therapeutic use of drugs. The Journal includes: -Clinical trials, outcomes research, clinical pharmacoeconomic studies and pharmacoepidemiology studies with a strong link to optimum prescribing practice for a drug or group of drugs. -Clinical pharmacodynamic and clinical pharmacokinetic studies with a strong link to clinical practice. -Pharmacodynamic and pharmacokinetic studies in healthy volunteers in which significant implications for clinical prescribing are discussed. -Studies focusing on the application of drug delivery technology in healthcare. -Short communications and case study reports that meet the above criteria will also be considered. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Clinical Drug Investigation may be accompanied by plain language summaries to assist readers who have some knowledge, but non in-depth expertise in, the area to understand important medical advances.