Liver damage indices as a tool for modifying methadone maintenance treatment: A cross-sectional study

Abstract

Aim To assess the effect of liver damage on methadone metabolism in opiate addicts undergoing methadone maintenance treatment (MMT). Methods This cross-sectional study recruited 74 patients treated at the outpatient clinic of Public Health Institute of Split-Dalmatia County from 2013-2016. Concentrations of methadone and its main inactive metabolite were measured in participants’ biological samples on regular checkups. Urine samples obtained before oral methadone intake, and blood and urine samples obtained 90 minutes after methadone intake were analyzed using gas chromatography/mass spectrometry. Participants were divided into groups according to liver damage criteria: hepatitis C virus status (positive, negative, or clinical remission); aspartate aminotransferase to platelet ratio (APRI) index (<0.7 and ≥0.7); and fibrosis-4 score (<1.45, 1.45-3.25, >3.25). Results Metabolic ratio and methadone metabolite concentration in plasma decreased linearly with HCV infection status by the factor of 1.67 (P= 0.001) and 2.2 (P= 0.043), respectively. Metabolic ratio in plasma decreased in patients with APRI index ≥0.7 by the average factor of 2.12 (P= 0.01) and methadone metabolite concentration in plasma decreased by the factor of 6.16 (P= 0.009). Metabolic ratio in urine decreased with the severity of fibrosis-4 score by the average factor of 1.63 (P= 0.008), whereas methadone metabolite concentration decreased by the factor of 3.53 (P= 0.007). Conclusion Liver damage decreases methadone metabolism. Indices of liver function should be calculated regularly during MMT for methadone dose titration.