• Eur. J. Clin. Pharmacol. · Jan 1996

    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.

    • C B Eap, T Finkbeiner, M Gastpar, N Scherbaum, K Powell, and P Baumann.
    • Département Universitaire de Psychiatrie Adulte, Hôpital de Cery, Prilly-Lausanne, Switzerland.
    • Eur. J. Clin. Pharmacol. 1996 Jan 1;50(5):385-9.

    MethodsTwenty-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.ResultsA 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).ConclusionAlthough 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.

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