Methadone Reduced Nevirapine Pharmacokinetic Parameters in People Living With HIV in Malaysia

Abstract

Introduction: The HIV epidemic in Malaysia predominantly affects males (90% of total HIV cases) mostly intravenous drugs users. Nevirapine-based of highly active antiretroviral therapy (HAART) once- or twice-daily dosage improve accessibility and effectiveness of antiretroviral treatment for HIV positive intravenous drug users (IDUs) receiving methadone maintenance treatment. Studies reported that concomitant administration of nevirapine with methadone reduced methadone plasma concentration. Since methadone and nevirapine were both known to be the substrate for cytochrome 2B6 (CYP 2B6), concomitant use of both drugs may affect nevirapine concentration too. However, methadone effect on nevirapine concentration is still unclear. This is a cross sectional study which reports how methadone co-administration affects the pharmacokinetic parameters of nevirapine in people living with HIV (PLHIV). Methods: 112 patients receiving nevirapine-based antiretroviral drugs were recruited. Seventeen were maintained with methadone without withdrawal symptoms. High-performance liquid chromatography was used to measure plasma nevirapine concentrations. Nevirapine population pharmacokinetics was modelled with a non-parametric approach using Pmetrics software. Result: According to univariate analysis, concurrent methadone administration increased the clearance of nevirapine by 25.3% (p = 0.046). Multivariate analysis showed that methadone medication was independently linked with lower nevirapine concentrations and area-under-curve (Cmin was reduced by 15.2%, p = 0.011, Cmax 19.5%; p = 0.003, AUC12 16.2%; p = 0.021 respectively). Conclusion: This study provides in-vivo evidence of methadone co-administration reducing nevirapine exposure. Since a low concentration of nevirapine will lead to treatment failure, monitoring is essential for PLHIV using both medications at the same time.