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 determine whether a blood concentration of (R)-methadone can be associated with therapeutic response in addict patients in methadone maintenance treatment. Trough 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 during a 2-month period prior to blood sampling. A large interindividual variability of (R)-methadone concentration-to-dose-to-weight ratios was found (mean, S.D., median, range: 112, 54, 100, 19-316 ng x kg/ml x mg). With regard 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 400 ng/ml) but not with (S)-methadone concentrations. A higher specificity was calculated for (R)- than for (R,S)-methadone, as the number of non-responders 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 concentration-to-dose-to-weight ratios, theoretical doses of racemic methadone could be as small as 55 mg/day and as large as 921 mg/day to produce a plasma (R)-methadone concentration of 250 ng/ml in a 70-kg patient. This demonstrates the importance of individualizing methadone treatment.
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Unité de Biochimie et Psychopharmacologie Clinique, Département Universitaire de Psychiatrie Adulte, Hôpital de Cery, CH-1008, Prilly-Lausanne, Switzerland. chin.eap@inst.hospvd.ch
Bourquin
M
M
Martin
J
J
Spagnoli
J
J
Livoti
S
S
Powell
K
K
Baumann
P
P
Déglon
J
J
D000328:Adult; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008691:Methadone / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D008875:Middle Aged; D009294:Narcotics / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D009293:Opioid-Related Disorders / Q000534:rehabilitation*; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
D009294:Narcotics; D008691:Methadone