Abstract Background Interpretation of urine buprenorphine and norbuprenorphine concentrations is widely used to assess adherence during treatment for opioid use disorder. However, the relationships between dose, timing of sample collection, and metabolite ratios remain unclear, leading to potential misinterpretation in clinical practice. Methods Data were collected from patients on a psychiatry unit who were either inducted on or continued buprenorphine therapy and underwent urine testing for buprenorphine and its metabolite, norbuprenorphine. Urine samples were collected 16 to 786 min after the last buprenorphine dose. Norbuprenorphine-to-buprenorphine ratios were calculated. Data analysis using Python included polynomial regression and random forest models. Results Daily buprenorphine doses ranged from 2 to 24 mg. A polynomial regression model predicting time since last dose, using urine buprenorphine concentration, norbuprenorphine-to-buprenorphine (NB/B) ratio, cumulative dose, daily dose, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), resulted in an R2 of 0.620 (P = 0.00006). A random forest model using time since last dose, daily dose of buprenorphine, and cumulative dose of buprenorphine to predict the NB/B ratio achieved an R2 of 0.762. No significant relationship was found between daily dose and urinary concentrations of buprenorphine, norbuprenorphine, or the NB/B ratio. Patient-specific variables like age and body mass index (BMI) were not significant predictors. The NB/B ratio alone was inadequate for estimating adherence, cumulative exposure, or recent dose. Conclusions Urine buprenorphine metabolite concentrations and NB/B ratios alone are insufficient for assessing adherence or guiding dose adjustments. Effective monitoring requires integrating metabolite data with clinical context, dosing history, and precise sample timing to inform treatment personalization and avoid misinterpretation.
Haykal et al. (2026) studied this question.