L-METHADONE AND D,L-METHADONE IN METHADONE-MAINTENANCE TREATMENT - A COMPARISON OF THERAPEUTIC EFFECTIVENESS AND PLASMA-CONCENTRATIONS

The clinical effectiveness of I-methadone maintenance treatment (LMMT) carried out using d,l-methadone or I-methadone have been compared wit h ambulatory heroin-dependent subjects. A total of 40 heroin-dependent subjects, previously maintained on I-methadone in Frankfurt am Main, were divided into two groups under randomised double-blind conditions and received either an equivalent dose of I-methadone as d,l-methadone or remained on the previous I-methadone treatment. Requests for a cha nge in the dose of d,l-methadone and I-methadone were recorded, urine samples for determination of illicit drug use were collected and the i ndividual level of opiate craving was determined over a 22-day observa tion period. There was no significant difference between the two group s ill the number requests for a dose change (dose increase < 10%). How ever, there was a significant increase in heroin use in the group whic h continued to receive I-methadone, Although there was less variabilit y in opiate craving in the group receiving d,l-methadone, the mean int ensity of opiate craving did not differ between the two groups. The me an I-methadone dose:l-methadone plasma concentration ratio, an index o f the bioavailability of I-methadone in individual subjects, showed no significant change when the treatment was changed to dl-methadone. Th e mean d-methadone:l-methadone plasma concentration ratio was 1.17. Th ere was no significant difference between these ratios for day 15 and day 22. The l-methadone:EDDP plasma concentration ratio in the l-metha done Stereoisomers group was 22.2 and the dl-methadone:EDDP plasma con centration ratio was 18.4. The plasma EDDP concentration in the d, I-m ethadone group increased 3-fold after starting treatment with d, I-met hadone. These findings suggest that d,l-methadone can be used in metha done maintenance treatment of heroin-dependent subjects but that furth er studies are required to evaluate pharmacokinetic interactions betwe en methadone enantiomers.