Compliance with Methadone-Based Substitutive Treatment: A Proposed Model Based on Immunoassay Urinary Sample Screening

Methadone (MTD) maintenance treatment is a recognized method to reduce illicit opiate abuse. Because of the difficulties of collecting 24-hour urines routinely, the monitoring of MTD compliance is currently done with random urinary screening. However, monitoring of MTD compliance by random urinary screening lacks accuracy because of its highly variable pharmacokinetics, leading to false positive or negative results. This study's objective was to identify factors influencing the reliability of urinary screening of methadone for MTD compliance monitoring in a field setting involving usual care for opiate-dependent patients. In a cross-sectional population-based study, 1981 urine samples obtained from 68 patients in parallel with drug dose, gender, and weight were analyzed by MTD enzyme immunoassay (EMITO). Urinary pH was measured, and positive threshold was determined experimentally by box-plot analysis. Multivariate determinants of MTD excretion were established with step-wise multiple regression analysis. On this basis, adjusted values for MTD excretion were proposed and verified with an (S)-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) assay from independent urine samples that were negative or doubtful by the MTD assay. MTD excretion was higher in men, decreased with increased urinary pH, and increased with daily dosage of MTD; these factors explain 32% of the total variance of urinary MTD. Adjustment on these 3 variables (urinary pH, sex, daily dosage) improved the prediction of compliance to MTD treatment. Threshold was stable across pH values and in agreement with EDDP results. The influence of simple variables such as gender, urinary pH, and daily dosage on urinary MTD excretion could be put in evidence and accounted for. Adjusted values of urinary MTD are more reliable than the raw values for monitoring compliance to MTD treatment.