Methadone Serum Concentration Monitoring in Palliative Care Patients with Cancer-Induced Bone Pain: A Short Communication

Background: Therapeutic drug monitoring of methadone for opioid replacement therapy in the management of opioid dependence is well-described. However, only a few studies have described the correlation between serum methadone concentration and cancer pain during palliative care. 

Methods: Patients were recruited from an exploratory randomized controlled trial (RCT) comparing methadone rotation with other opioid rotations for refractory cancer-induced bone pain. Serum methadone trough levels and 2-ethylidene-1,5-dimethyl-3,3-diphe-nylpyrrolidine (EDDP) levels on day 14 of the rotation were analyzed using validated liquid chromatography-mass spectrometry. The average and worst pain intensities were rated at baseline and on day 14, preceding the recorded methadone levels. The Common Terminology Criteria for Adverse Events composite score was used to determine the adverse effects of methadone. The Spearman r was used to examine the correlation between methadone trough levels and pain reduction. 

Results: Among the 20 patients who were randomized to receive methadone in the RCT, eight consented to this substudy. The mean (SD) steady-state 24-hour methadone dose was 11.6 (2.6) mg, whereas the mean (SD) serum methadone trough concentration was 93.7 (45.6) ng/mL with an acceptable adverse effect profile. All patients had an EDDP concentration of,0.01 mg/L, suggesting good metabolite clearance. 

Conclusions: The reported methadone concentration required for therapeutic benefit was significantly lower than that reported previously. The study highlights that further appropriately powered studies are required to establish the role of routine trough methadone monitoring in patients newly rotated for the management of refractory cancer pain.