Metabolism, pharmacokinetics and selected pharmacodynamic effects of codeine following a single oral administration to horses

Sophie R. Gretler, Carrie J Finno, Daniel S. McKemie, Philip H. Kass, Heather K Knych

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Objective: To describe the pharmacokinetics and selected pharmacodynamic variables of codeine and its metabolites in Thoroughbred horses following a single oral administration. Study design: Prospective experimental study. Animals: A total of 12 Thoroughbred horses, nine geldings and three mares, aged 4–8 years. Methods: Horses were administered codeine (0.6 mg kg–1) orally and blood was collected before administration and at various times until 120 hours post administration. Plasma and urine samples were collected and analyzed for codeine and its metabolites by liquid chromatography–mass spectrometry, and plasma pharmacokinetics were determined. Heart rate and rhythm, step counts, packed cell volume and total plasma protein were measured before and 4 hours after administration. Results: Codeine was rapidly converted to the metabolites norcodeine, codeine-6-glucuronide (C6G), morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Plasma codeine concentrations were best represented using a two-compartment model. The Cmax, tmax and elimination t½ were 270.7 ± 136.0 ng mL–1, 0.438 ± 0.156 hours and 2.00 ± 0.534 hours, respectively. M3G was the main metabolite detected (Cmax 492.7 ± 35.5 ng mL–1), followed by C6G (Cmax 96.1 ± 33.8 ng mL–1) and M6G (Cmax 22.3 ± 4.96 ng mL–1). Morphine and norcodeine were the least abundant metabolites with Cmax of 3.17 ± 0.95 and 1.42 ± 0.79 ng mL–1, respectively. No significant adverse or excitatory effects were observed. Conclusions and clinical relevance: Following oral administration, codeine is rapidly metabolized to morphine, M3G, M6G, C6G and norcodeine in horses. Plasma concentrations of M6G, a presumed active metabolite of morphine, were comparable to concentrations reported previously following administration of an analgesic dose of morphine to horses. Codeine was well tolerated based on pharmacodynamic variables and behavioral observations.

Original languageEnglish (US)
JournalVeterinary Anaesthesia and Analgesia
StateAccepted/In press - 2020


  • codeine
  • horse
  • metabolism
  • pharmacodynamics
  • pharmacokinetics

ASJC Scopus subject areas

  • veterinary(all)


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