Davanço Marcelo Gomes, Fortuny Miguel, Scasso Alejandro, Meulman Jessica, Costa Fernando, da Silva Thalita Martins, Vianna Débora Renz Barreto, Teixeira Leonardo de Souza, Bellorio Karini Bruno, Sampaio Ana Carolina Costa, Vespasiano Celso Francisco Pimentel
Clinical Research Unit, Adium S.A., São Paulo 04794-000, Brazil.
R&D Department, Amarin Technologies S.A., Buenos Aires C1416BQG, Argentina.
Pharmaceutics. 2024 Sep 26;16(10):1249. doi: 10.3390/pharmaceutics16101249.
Buprenorphine is an opioid drug indicated for the management of severe and persistent pain. The buprenorphine transdermal patch provides a non-invasive method of rate-controlled drug release, ensuring constant and predictable drug plasma levels over an extended period. This study aimed to assess the bioequivalence, skin adhesion non-inferiority, and tolerability of two buprenorphine transdermal patches to meet the regulatory requirements for the registration of a generic product in Brazil. A randomized, single-dose, two-period, two-sequence crossover trial was performed involving healthy subjects of both genders. The subjects received a single dose of either the test formulation or the reference formulation (Restiva), separated by a 29-day washout period. For pharmacokinetic analysis, blood samples were collected up to 12 days post-dose and quantified using a validated bioanalytical method. Skin adhesion was assessed over a 7-day period (dosing interval) following patch application. Seventy-six subjects were enrolled and fifty-two completed the study. The 90% confidence intervals for Cmax, AUC, and partial AUCs were within the acceptable bioequivalence limits of 80 to 125%. Adhesion comparison showed the non-inferiority of the test formulation. Based on ANVISA's regulatory requirements, the test and reference formulations were considered bioequivalent and could be interchangeable in clinical practice.
丁丙诺啡是一种用于管理严重和持续性疼痛的阿片类药物。丁丙诺啡透皮贴剂提供了一种非侵入性的速率控制药物释放方法，可确保在较长时间内药物血浆水平恒定且可预测。本研究旨在评估两种丁丙诺啡透皮贴剂的生物等效性、皮肤粘附非劣效性和耐受性，以满足巴西通用产品注册的监管要求。进行了一项随机、单剂量、两期、两序列交叉试验，纳入了男女健康受试者。受试者接受单剂量的试验制剂或参比制剂（Restiva），中间间隔29天的洗脱期。为进行药代动力学分析，在给药后12天内采集血样，并使用经过验证的生物分析方法进行定量。在贴剂应用后的7天（给药间隔）内评估皮肤粘附情况。共招募了76名受试者，52名完成了研究。Cmax、AUC和部分AUC的90%置信区间在80%至125%的可接受生物等效性限度内。粘附性比较显示试验制剂非劣效。根据巴西国家卫生监督局（ANVISA）的监管要求，试验制剂和参比制剂被认为具有生物等效性，在临床实践中可互换使用。
