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
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