Utilization of plasma and urine methadone concentration measurements to limit narcotics use in methadone maintenance patients: II. Generation of plasma concentration response curves.

Controversy exists still concerning the proper daily dose of methadone required to eliminate illicit narcotics use. To address this, urine methadone and opioid concentrations were measured prospectively (150 maintenance patients, 18 month period, 9250 urine samples) using fluorescence polarization immunoassay. Results demonstrate that current thresholds (EMIT uses 300 micrograms/L) defining opiate positive urines are overly high (FPIA can go as low as 25 micrograms/L), causing severe underestimation of opioid use in the typical clinic. Using this data, plasma methadone concentration and dose response probability curves were generated for illicit opiate use. Results demonstrate a S-shaped, 24 hr trough plasma methadone concentration response curve with effective concentrations, EC90 = 80 micrograms/L, EC98 = 600 micrograms/L. Plotting mean plasma methadone concentration versus dose gives a monotonically increasing function: Conc = 5.367*dose0.858, raw R-squared = 0.967, corrected R-squared = 0.802. Unfortunately, coefficients of variation for plasma concentrations at each prescribed dose are unacceptably large, explaining poor dose response relationships for some patients.