Distinct Relations Among Plasma Concentrations Required for Different Pharmacological Effects in Oxycodone, Morphine, and Fentanyl
- 11 November 2011
- journal article
- Published by Taylor & Francis Ltd in Journal of Pain & Palliative Care Pharmacotherapy
- Vol. 25 (4), 318-334
- https://doi.org/10.3109/15360288.2011.620689
Abstract
Several clinical reports showed that adverse effect profiles are not the same in morphine, oxycodone, and fentanyl. The authors investigated whether the relationship between plasma concentrations for antinociceptive effect and for various pharmacological effects differed among oxycodone, morphine, and fentanyl under controlled experimental setting using animal models. Oxycodone induced constipation and an antinociceptive effect in a similar concentration-dependent manner, whereas morphine required approximately 9-fold higher plasma concentration for antinociceptive effect compared with that for constipation when 50% effective plasma concentration (EC50) levels were compared. The EC50 values for inhibition of behavioral activity were 2.1-, 2.7-, and 1.3-fold higher than those for antinociceptive effect in oxycodone, morphine, and fentanyl, respectively. Respiratory inhibition was observed even at higher plasma concentrations in all three opioids, and the differences in the EC50 values compared with those for antinociceptive effects were 234.5-fold (oxycodone), 233.1-fold (morphine), or 104.2-fold (fentanyl). These results showed that oxycodone, morphine, and fentanyl exhibited unique patterns of plasma concentrations required for different pharmacological effects. The different adverse effect profiles observed in a clinical setting appear to be resulted from, at least in part, distinct intrinsic pharmacological profiles among these μ-opioid receptor agonists.Keywords
This publication has 22 references indexed in Scilit:
- μ-Opioid Receptors: Correlation of Agonist Efficacy for Signalling with Ability to Activate InternalizationMolecular Pharmacology, 2010
- Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actionsProceedings of the National Academy of Sciences of the United States of America, 2009
- Opioid Rotation from Oral Morphine to Oral Oxycodone in Cancer Patients with Intolerable Adverse Effects: An Open-Label TrialJapanese Journal of Clinical Oncology, 2008
- The evasive nature of drug efficacy: implications for drug discoveryTrends in Pharmacological Sciences, 2007
- Treatment of opioid-induced gut dysfunctionExpert Opinion on Investigational Drugs, 2007
- Morphine, Oxycodone, Methadone and Its Enantiomers in Different Models of Nociception in the RatAnesthesia & Analgesia, 2006
- Pharmacokinetic–Pharmacodynamic Modeling of OpioidsJournal of Pain and Symptom Management, 2005
- Possible involvement of μ1-opioid receptors in the fentanyl- or morphine-induced antinociception at supraspinal and spinal sitesLife Sciences, 2002
- Psychostimulants as adjuvant analgesicsJournal of Pain and Symptom Management, 1994
- Adverse Effects of Systemic Opioid AnalgesicsDrug Safety, 1992