Transdermal Buprenorphine for Opiate Antagonist Therapy

描述(申请人提供)：阿片拮抗剂疗法是最近戒断的阿片成瘾者的重要治疗方法。丁丙诺啡是一种混合激动剂和拮抗剂，它通过阻断主观阿片奖励来消除生理强化。丁丙诺啡最近以舌下片的形式上市，非常有效，是美沙酮或纳曲酮受试者的首选。Biotek建议通过开发3天经皮给药系统来改进丁丙诺啡的治疗。这样的贴片将提供稳定的激动剂治疗，以促进依从性。如果这样的贴片能够含有相对较少的丁丙诺啡，颠覆和滥用的动机将是微乎其微的。在第一阶段获得的人体皮肤体外实验结果强烈支持这种贴剂的可行性，而对兔的刺激性研究表明它将是无刺激性的。阶段 II将建立适用于GMP生产的贴片规格，确认所选制剂的体外性能，制备和表征GMP临床样品，启动稳定性研究，提交IND，并进行安全性和药代动力学的初步人体研究。

DESCRIPTION (provided by applicant): Opiate antagonist therapy is an important treatment for recently withdrawn opiate addicts. Buprenorphine is a mixed agonist-antagonist which eliminates physiological reinforcement by blocking subjective opiate reward. Recently marketed as sublingual tablets, buprenorphine is very effective and is preferred by subjects to methadone or naltrexone. BIOTEK proposes to improve buprenorphine therapy by developing a 3-day transdermal delivery system. Such a patch would provide steady maintenance of agonist therapy to foster compliance. If such a patch can be made to contain relatively little buprenorphine, the motivation for subversion and abuse will be minimal. In vitro results on human skin obtained during Phase I strongly support the feasibility of such a patch, and rabbit irritation studies suggest that it will be non-irritating. Phase II will establish patch specifications suitable for GMP manufacture, confirm the in vitro performance of the selected formulation, prepare and characterize GMP clinical samples, initiate stability studies, submit an IND, and conduct an initial human study of safety and pharmacokinetics.