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  • Title: Pharmacokinetics and pharmacodynamics of methadone enantiomers in hospice patients with cancer pain.
    Author: Auret K, Roger Goucke C, Ilett KF, Page-Sharp M, Boyd F, Oh TE.
    Journal: Ther Drug Monit; 2006 Jun; 28(3):359-66. PubMed ID: 16778720.
    Abstract:
    Racemic methadone is increasingly used to manage cancer pain. The authors studied 13 terminally ill patients with cancer pain, who underwent switching (rotation) from morphine to methadone. The relationship between initial morphine dose and final methadone dose, the pharmacokinetics of R- and S- methadone, and the degree of pain control and side effects were investigated. Preswitching serum morphine concentrations and second daily plasma concentrations of methadone were measured. The brief pain inventory (BPI) was used to assess pain every second day. "Worst pain" as measured by the BPI improved by >/=20% in 6 of the 13 patients. The mean morphine to methadone conversion ratio was 5.2 with wide interpatient variability (range 1.3 to 11). Average steady-state concentrations were 197 (98 to 379) mug/L and 272 (55 to 378) mug/L for R- and S-methadone, respectively. Mean population pharmacokinetic parameters for a 1-compartment model were 455 L and 338 L for apparent volume of distribution and 53.3 hours and 31.5 hours for half-life for R- and S- methadone, respectively. Bayesian estimates of apparent oral clearance for individual patients were 0.082 (0.052 to 0.112) L/kg/h and 0.117 (0.061 to 0.173) L/kg/h for R- and S- methadone, respectively (mean and 95% confidence interval). The low and variable clearance values generally resulted in slow achievement of steady-state concentrations over several days; inappropriately high plasma methadone levels occurred in 1 patient. Whereas optimal pain control was achieved in 46% of patients, there was no relationship with plasma concentrations of methadone. Best practice for methadone use in this patient group should include monitoring of both pain and methadone concentration.
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