Pharmacokinetics and pharmacodynamics of methadone in patients with chronic pain Journal Article
| Authors: | Inturrisi, C. E.; Colburn, W. A.; Kaiko, R. F.; Houde, R. W.; Foley, K. M. |
| Article Title: | Pharmacokinetics and pharmacodynamics of methadone in patients with chronic pain |
| Abstract: | Concentrations of methadone in plasma, estimates of pain relief, and pupillary size were determined after a single intravenous dose (10 to 30 mg) of methadone hydrochloride to eight patients with chronic pain, five of whom had cancer. The pharmacokinetic parameter estimates reveal rapid and extensive distribution (Varea) and a slow apparent elimination half-life (t1 2) (mean Varea = 3.59 L/kg and harmonic mean t1 2 = 23 hours). The harmonic mean blood clearance is 106 ml/min, the harmonic mean renal clearance is 3.9 ml/min, the mean hepatic extraction ratio is 0.089, and plasma protein binding is 86% to 89%. These results suggest that only the free (unbound) fraction of methadone present in blood is extracted by the liver and that methadone can be classified as a low (hepatic)-extraction drug. The data were fit to a pharmacokinetic-pharmacodynamic model to obtain estimates of the steady-state plasma methadone concentration required to produce 50% of the maximum pain relief. This value varied from 0.04 to 1.13 μg/ml (mean = 0.29 μg/ml). These results indicate substantial interindividual variation in the relationship between changes in plasma methadone concentration and analgesia in patients with chronic pain receiving opioids. A pharmacokinetic-pharmacodynamic model may be useful for the individualization of analgesic dosage and therefore the optimization of pain management in patients with chronic pain. © 1987. |
| Keywords: | adult; aged; middle aged; major clinical study; blood proteins; pain; pharmacodynamics; cancer pain; central nervous system; chronic disease; pethidine; kinetics; blood pressure; chronic pain; methadone; morphine; drug therapy; hydromorphone; analgesia; therapy; half-life; intravenous drug administration; pharmacokinetics; levorphanol; oxycodone; visual system; cancer; humans; human; male; female; priority journal; pupil |
| Journal Title: | Clinical Pharmacology & Therapeutics |
| Volume: | 41 |
| Issue: | 4 |
| ISSN: | 0009-9236 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1987-04-01 |
| Start Page: | 392 |
| End Page: | 401 |
| Language: | English |
| DOI: | 10.1038/clpt.1987.47 |
| PUBMED: | 3829576 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 5 February 2021 -- Source: Scopus |
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