Inhibition of morphine metabolism by ketamine

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Xiaoxin QiRobert W Milne

Abstract

Clinical observation of a synergistic effect of ketamine on morphine analgesia remains controversial. Although a pharmacodynamic basis for an interaction has been explored in animal and clinical studies, the possibility of a pharmacokinetic mechanism has not been investigated. Whereas both morphine and morphine-6-glucuronide are effective analgesics, morphine-3-glucuronide (M3G) lacks activity. Thus, changes in the metabolism and disposition of morphine may result in an altered response. First, we investigated the interaction between morphine and ketamine in the isolated perfused rat liver preparation. The clearance of morphine was decreased from 16.8 +/- 4.6 ml/min in the control period to 7.7 +/- 2.8 ml/min in the ketamine-treatment period, with the formation clearance of M3G decreasing from 8.0 +/- 4.1 ml/min to 2.1 +/- 1.1 ml/min. Fractional conversion of morphine to M3G was significantly decreased from 0.46 +/- 0.17 in the control period to 0.28 +/- 0.14 upon the addition of ketamine. The possible mechanism of the interaction was further investigated in vitro with rat liver microsomes as the enzyme source. The formation of M3G followed single-enzyme Michaelis-Menten kinetics, with a mean apparent K(m) of 2.18 +/- 0.45 mM a...Continue Reading

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Citations

Jun 17, 2011·The Clinical Journal of Pain·Howard S Smith
Sep 23, 2014·International Journal of Pediatric Otorhinolaryngology·Gillian Lauder, Anthony Emmott
Apr 26, 2016·Anesthesiology and Pain Medicine·Kianoush SaberiFarinaz Nasiri Nejad
Oct 9, 2012·Peptides·Richard J Bodnar
Oct 9, 2012·The American Journal of Emergency Medicine·John R Richards, Rachel E Rockford
Jan 29, 2014·Paediatric Anaesthesia·Brian J Anderson, John van den Anker
Nov 25, 2017·Basic & Clinical Pharmacology & Toxicology·Tuomas O LiliusPekka V Rauhala
Jun 12, 2018·Expert Opinion on Drug Metabolism & Toxicology·Jui-Tai ChenRuei-Ming Chen
Feb 12, 2017·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jasmina TurkanovicRobert W Milne
Apr 14, 2018·Drugs·Sophia Sheikh, Phyllis Hendry
Feb 20, 2017·Forensic Sciences Research·Ricardo Jorge Dinis-Oliveira
Nov 17, 2019·Journal of Clinical Laboratory Analysis·Hua FangJian-Ping Zhang

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