METHADONE AND HIV/AIDS DRUG INTERACTIONS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究旨在改善美沙酮维持治疗，这是阿片类药物滥用治疗和降低艾滋病毒/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会导致鸦片类药物戒断、副作用和艾滋病毒治疗失败。美沙酮的首过代谢和全身清除是由细胞色素P450、细胞色素P450、细胞色素P450B和细胞色素P3A催化的。CYP的可变性和药物相互作用会影响美沙酮的代谢。HIV蛋白水解酶抑制剂(HIV-PI)是一种有效的CYP调节剂，可与美沙酮和许多其他药物产生显著、复杂且鲜为人知的相互作用。本研究旨在明确HIV-PI-美沙酮相互作用的机制(S)，特别是利托那韦-洛匹那韦，评价其对正常志愿者肠道细胞色素P3A活性和首过美沙酮代谢、肝脏细胞色素P3A和美沙酮清除、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疗效。

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