Department of Psychiatry, University of California San Francisco, CA, USA.
Clin Infect Dis. 2012 Feb 1;54(3):414-23. doi: 10.1093/cid/cir799. Epub 2011 Nov 18.
This study examined drug interactions between buprenorphine, a partial opioid agonist used for opioid dependence treatment and pain management, and the protease inhibitors (PIs) darunavir-ritonavir and fosamprenavir-ritonavir.
The pharmacokinetics of buprenorphine and its metabolites and symptoms of opioid withdrawal or excess were compared in opioid-dependent, buprenorphine-naloxone-maintained, human immunodeficiency virus (HIV)-negative volunteers (11 for darunavir-ritonavir and 10 for fosamprenavir-ritonavir) before and after 15 days of PI administration. PI pharmacokinetics and adverse effects were compared between the buprenorphine-maintained participants and an equal number of sex-, age-, race-, and weight-matched, healthy, non-opioid-dependent volunteers who received darunavir-ritonavir or fosamprenavir-ritonavir but not buprenorphine.
There were no significant changes in buprenorphine or PI plasma levels and no significant changes in medication adverse effects or opioid withdrawal. Increased concentrations of the inactive metabolite buprenorphine-3-glucuronide suggested that darunavir-ritonavir and fosamprenavir-ritonavir induced glucuronidation of buprenorphine.
Dose adjustments are not likely to be necessary when buprenorphine and darunavir-ritonavir or fosamprenavir-ritonavir are coadministered for the treatment of opioid dependence and HIV disease.
本研究考察了丁丙诺啡(一种用于治疗阿片类药物依赖和疼痛管理的部分阿片激动剂)与蛋白酶抑制剂(PI)达芦那韦-利托那韦和福沙那韦-利托那韦之间的药物相互作用。
在开始接受 PI 治疗的 15 天前后,比较了丁丙诺啡-纳洛酮维持的、人类免疫缺陷病毒(HIV)阴性的阿片类药物依赖志愿者(达芦那韦-利托那韦组 11 人,福沙那韦-利托那韦组 10 人)的丁丙诺啡及其代谢物的药代动力学和阿片类药物戒断或过量的症状。还比较了丁丙诺啡维持组与接受达芦那韦-利托那韦或福沙那韦-利托那韦但未接受丁丙诺啡的、数量相同的、性别、年龄、种族和体重匹配的、健康的、非阿片类药物依赖志愿者的 PI 药代动力学和不良反应。
丁丙诺啡或 PI 的血浆水平没有显著变化,药物不良反应或阿片类药物戒断也没有显著变化。无活性代谢物丁丙诺啡-3-葡糖苷酸的浓度增加表明,达芦那韦-利托那韦和福沙那韦-利托那韦诱导了丁丙诺啡的葡糖苷酸化。
当丁丙诺啡与达芦那韦-利托那韦或福沙那韦-利托那韦联合用于治疗阿片类药物依赖和 HIV 疾病时,不需要调整剂量。