Replacement of (R)-methadone by a double dose of (R,S)-methadone in addicts: Interindividual variability of the (R)/(S) ratios and evidence of adaptive changes in methadone pharmacokinetics

被引:76
作者
Eap, CB [1 ]
Finkbeiner, T [1 ]
Gastpar, M [1 ]
Scherbaum, N [1 ]
Powell, K [1 ]
Baumann, P [1 ]
机构
[1] RHEIN LAND & HSCH KLIN ESSEN,D-45030 ESSEN,GERMANY
关键词
methadone; enantiomer; metabolism; induction; opioid addicts;
D O I
10.1007/s002280050128
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Methods: Twenty-two patients receiving (R)-methadone maintenance treatment were switched to a double dose of (R, S)-methadone: blood samples were collected before and after the change, and the concentrations of the enantiomers were measured. In the second period, during racemic methadone treatment, important interindividual variability in the stereoselective disposition of the enantiomers of methadone was measured, with (R)/(S) ratios ranging from 0.63 to 2.40. This point should be taken into account particularly with respect to therapeutic drug monitoring of racemic methadone. Results: A significant decrease P < 0.005 in the mean serum concentration/dose ratios of the active (R)-enantiomer before and after the change was measured (mean 3.97 and 3.33). Conclusion: Although of small amplitude (16%), this decrease confirms previously described adaptive changes in methadone pharmacokinetics during racemic methadone maintenance treatment and may necessitate, in some patients, a dose adjustment.
引用
收藏
页码:385 / 389
页数:5
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