METHADONE AND HIV/AIDS DRUG INTERACTIONS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本研究旨在改善阿片类药物滥用治疗和降低艾滋病毒/艾滋病风险的基石美沙酮维持治疗，改善艾滋病毒/艾滋病治疗。美沙酮处置的可变性导致阿片戒断、副作用和HIV治疗失败。细胞色素p4500s CYP2B和CYP3A催化美沙酮的首过代谢和全身清除。CYP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）是有效的CYP调节剂，与美沙酮和许多其他药物产生重要的、复杂的、鲜为人知的相互作用。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，评估对正常志愿者肠道CYP3A活性和美沙酮首过代谢、肝脏CYP3A和美沙酮清除、肠道p-糖蛋白（P-gp）活性和美沙酮吸收和临床效果的影响

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