Plasma concentrations of the enantiomers of methadone and therapeutic response in methadone maintenance treatment

Methadone is a 50:50 mixture of two enantiomers and (R)-methadone accounts for the majority of its opioid effect. The aim of this study was to determi ne whether a blood concentration of (R)-methadone can be associated with th erapeutic response in addict patients in methadone maintenance treatment. T rough plasma concentrations of (R)-, (S)- and (R,S)-methadone were measured in 180 patients in maintenance treatment. Therapeutic response was defined by the absence of illicit opiate or cocaine in urine samples collected dur ing a 2-month period prior to blood sampling. A large interindividual varia bility of (R)-methadone concentration-to-dose-to-weight ratios was found (m ean, S.D., median, range: 112, 54, 100, 19-316 ng x kg/ml x mg). With regar d to the consumption of illicit opiate (but not of cocaine), a therapeutic response was associated with (R)- (at 250 ng/ml) and (R,S)-methadone (at 40 0 ng/ml) but not with (S)-methadone concentrations. A higher specificity wa s calculated for (R)- than for (R,S)-methadone, as the number of non-respon ders above this threshold divided by the total number of non-responders was higher for (R,S)-methadone (19%) than for (R)-methadone (7%). The results support the use of therapeutic drug monitoring of (R)-methadone in cases of continued intake of illicit opiates. Due to the variability of methadone c oncentration-to-dose-to-weight ratios, theoretical doses of racemic methado ne could be as small as 55 mg/day and as large as 921 mg/day to produce a p lasma (R)-methadone concentration of 250 ng/ml in a 70-kg patient. This dem onstrates the importance of individualizing methadone treatment. (C) 2000 E lsevier Science Ireland Ltd. All rights reserved.