Therapeutic Drug Monitoring in Buprenorphine/Naloxone Treatment for Opioid Use Disorder: Clinical Feasibility and Optimizing Assay Precision

Abstract

Introduction Compliance with sublingual buprenorphine/naloxone (SL-BUP/NX) is associated with higher abstinence from illicit opioid use. Therapeutic drug monitoring (TDM) has been recommended for adherence monitoring of buprenorphine (BUP) maintenance treatment for opioid use disorder (OUD), but to date there have been no reported clinical applications. In this TDM feasibility study, we investigated BUP assay precision in 15 adults with OUD who had been stabilized on buprenorphine/naloxone. Methods Using solid phase extraction, BUP recovery was contrasted at 100 mMol and 1 Molar of acetic acid wash solution. Precision was determined by applying the condition generating highest recovery using 0.2 ng/mL and 10 ng/mL standards. Four blood samples were drawn to examine the BUP peak and trough plasma concentrations, and BUP elimination rate was estimated. BUP recovery was examined again in a random sample and contrasted with the concentration predicted applying first-order kinetics. Results Higher BUP recovery was achieved with 1 Molar wash (94.3%; p=0.05). Precision ranged from 15–20%. The estimated limit of detection (LoD) and limit of quantitation (LoQ) were 0.02 and 0.069 ng/mL, respectively. BUP peak and trough concentrations were successfully examined, and BUP trough concentrations were replicated confirming steady state. BUP concentrations were predicted at a variance of −7.20% to 1.54 %. Conclusions TDM for BUP maintenance treatment of OUD is feasible, and simple adjustment of the assay conditions enhances BUP recovery.

Lower buprenorphine elimination rate constant is associated with lower opioid use

“…The first sample was drawn 40 min post the BUP dose representing the peak plasma concentration; the second sample was drawn 30 min prior to the BUP/NX-F dose representing trough plasma concentration and repeated 48 h later. Applying a pharmacokinetic model, the measured peak and trough BUP concentrations at steady-state concentration were used to estimate the BUP EL.R constant (Elarabi et al 2020 ) during the inpatient treatment. Quantitation of BUP was done using liquid chromatography tandem spectrometry according validated method that was tested for clinical feasibility and accuracy.…”

“…Quantitation of BUP was done using liquid chromatography tandem spectrometry according validated method that was tested for clinical feasibility and accuracy. A fourth blood sample was drawn at random and BUP plasma level was quantified to validate the estimated BUP elimination rate during the pilot phase to demonstrate the feasibility and reliability of therapeutic drug monitoring (TDM) and pharmacokinetic model adopted in this trial (Elarabi et al 2020 ).…”

Effectiveness of incentivised adherence and abstinence monitoring in buprenorphine maintenance: a pragmatic, randomised controlled trial

“…On arrival, they were given their dose of BUP, they took a UDS and had a blood sample drawn. A pharmacokinetic model was applied to predict BUP concentration [15]. If the UDS confirmed abstinence for opioids and was positive for BUP, the participant was given a further 14‐day supply (with same directions) and asked to return to the clinic 2 weeks later. On return to the clinic, the procedure was repeated and the predicted BUP concentration (estimated from the previous visit) was contrasted with the BUP concentration on the day.…”

“…On arrival, they were given their dose of BUP, they took a UDS and had a blood sample drawn. A pharmacokinetic model was applied to predict BUP concentration [15]. If the UDS confirmed abstinence for opioids and was positive for BUP, the participant was given a further 14-day supply (with same directions) and asked to return to the clinic 2 weeks later.…”

“…Accordingly, this study is a contribution toward closing this gap. As a precursor, we optimised a laboratory quantification method for BUP monitoring, demonstrating that this was feasible during routine clinical operations [15]. Including TDM procedures, we developed a novel incentivised medication adherence and abstinence monitoring (I‐AAM) protocol.…”