1. Pharmacokinetics and effects of codeine in combination with acetaminophen on thermal nociception in horses.
- Author
-
Tueshaus T, McKemie DS, Kanarr K, Kass PH, and Knych HK
- Subjects
- Humans, Horses, Animals, Nociception, Drug Therapy, Combination veterinary, Codeine therapeutic use, Codeine adverse effects, Analgesics therapeutic use, Pain, Postoperative drug therapy, Pain, Postoperative veterinary, Drug Combinations, Double-Blind Method, Acetaminophen therapeutic use, Horse Diseases drug therapy
- Abstract
Codeine and acetaminophen in combination have proven to be an effective analgesic treatment for moderate-to-severe and postoperative pain in humans. Studies have demonstrated that codeine and acetaminophen, when administered as sole agents, are well tolerated by horses. In the current study, we hypothesized that administration of the combination of codeine and acetaminophen would result in a significant thermal antinociceptive effect compared with administration of either alone. Six horses were administered oral doses of codeine (1.2 mg/kg), acetaminophen (20 mg/kg), and codeine plus acetaminophen (1.2 mg/kg codeine and 6-6.4 mg/kg acetaminophen) in a three-way balanced crossover design. Plasma samples were collected, concentrations of drug and metabolites determined via liquid chromatography-mass spectrometry, and pharmacokinetic analyses were performed. Pharmacodynamic outcomes, including effect on thermal thresholds, were assessed. Codeine C
max and AUC were significantly different between the codeine and combination group. There was considerable inter-individual variation in the pharmacokinetic parameters for codeine, acetaminophen, and their metabolites in horses. All treatments were well tolerated with minimal significant adverse effects. An increase in the thermal threshold was noted at 1.5 and 2 h, from 15 min through 6 h and 0.5, 1, 1.5, and 3 h in the codeine, acetaminophen, and combination groups, respectively., (© 2023 John Wiley & Sons Ltd.)- Published
- 2023
- Full Text
- View/download PDF