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Pharmacokinetic‐pharmacodynamic relationships of methadone infusions in patients with cancer pain
Author(s) -
Inturrisi Charles E,
Portenoy Russell K,
Max Mitchell B,
Colburn Wayne A,
Foley Kathleen M
Publication year - 1990
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1990.77
Subject(s) - methadone , pharmacodynamics , sedation , anesthesia , medicine , cancer pain , pharmacokinetics , opioid , clinical pharmacology , pain relief , pharmacology , cancer , receptor
To determine the relationship between changes in plasma methadone concentration and pharmacodynamic effects, plasma methadone profiles and pharmacodynamics (analgesia and sedation) were measured during and after the continuous infusion of methadone for 180 to 270 minutes in 15 patients with pain caused by cancer. An increase in plasma methadone concentration resulted in a rapid increase in pain relief or sedation. The estimates of values of 50% of maximum effect (C ss 50) for pain relief and sedation obtained with a pharmacokinetic‐pharmacodynamic model varied tenfold to twentyfold among patients; the mean C ss 50 value for pain relief (0.359 ± 0.158 [SD] μg/ml) was virtually the same as the mean C ss 50 value for sedation (0.336 ± 0.205 [SD] μg/ml). Similarly, the mean γ (slope function) for pain relief (4.4 ± 3.8 [SD]) and sedation (5.8 ± 5.4 [SD]) did not differ. Examination of hysteresis plots of data obtained during the infusion and for 4 to 5 hours after cessation of the infusion revealed a very rapid equilibration between plasma methadone values and the sites mediating pain relief. There was no indication of the development of tolerance to the pharmacodynamic effects of methadone during the study. This report describes a method for quantitating the pharmacokinetic‐pharmacodynamic relationships of the desirable and undesirable effects of opioid analgesics. Clinical Pharmacology and Therapeutics (1990) 47, 565–577; doi: 10.1038/clpt.1990.77