METHADONE AND HIV/AIDS DRUG INTERACTIONS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。这项研究旨在改善美沙酮维持治疗，阿片类药物滥用治疗和减少艾滋病毒/艾滋病风险的基石，并改善艾滋病毒/艾滋病治疗。美沙酮处置的变异性导致阿片类药物戒断、副作用和艾滋病毒治疗失败。美沙酮首过代谢和全身清除由细胞色素P450的CYP 2B和CYP 3A催化。药物变异性和药物相互作用可影响美沙酮代谢。HIV蛋白酶抑制剂（HIV-PI）是一种有效的抗HIV药物，与美沙酮和许多其他药物之间存在显著的、复杂的和知之甚少的相互作用。本研究旨在确定HIV-PI-美沙酮相互作用的机制，特别是利托那韦-洛匹那韦，评价对正常志愿者肠道CYP 3A活性和首过美沙酮代谢、肝脏CYP 3A和美沙酮清除率、肠道P-糖蛋白（P-gp）活性和P-gp-美沙酮吸收的影响以及临床效应

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This research aims to improve methadone maintenance treatment, the cornerstone of opiate abuse therapy and HIV/AIDS risk reduction, and improve HIV/AIDS treatment. Variability in methadone disposition causes opiate withdrawal, side effects and HIV treatment failures. Methadone first-pass metabolism and systemic clearance are catalyzed by cytochrome P450s CYP2B and CYP3A. CYP variability and drug interactions can affect methadone metabolism. The HIV protease inhibitors (HIV-PI) are potent CYP modulators, causing significant, complex and poorly understood interactions with methadone and numerous other drugs. This study aims to identify the mechanism(s) of HIV-PI-methadone interactions, specifically ritonavir-lopinavir, evaluating effects on intestinal CYP3A activity and first -pass methadone metabolism, hepatic CYP3A and methadone clearance, and intestinal P-glycoprotein (P-gp) activity and P-gp-methadone absorption and clinical effects in normal volunteers