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

Citation
Cb. Eap et al., Plasma concentrations of the enantiomers of methadone and therapeutic response in methadone maintenance treatment, DRUG AL DEP, 61(1), 2000, pp. 47-54
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
DRUG AND ALCOHOL DEPENDENCE
ISSN journal
0376-8716 → ACNP
Volume
61
Issue
1
Year of publication
2000
Pages
47 - 54
Database
ISI
SICI code
0376-8716(200012)61:1<47:PCOTEO>2.0.ZU;2-I
Abstract
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.