title: Pharmacokinetics and pharmacodynamics of oral acetaminophen in combination with codeine in healthy Greyhound dogs.
abstract: The purpose of this study was to determine the pharmacokinetic and antinociceptive effects of an acetaminophen/codeine combination administered orally to six healthy greyhounds. Antinociception was assessed using an electronic von Frey (vF) device as a mechanical/pressure model. Acetaminophen was administered at a dose of 600 mg (14.4-23.1 mg/kg) and codeine phosphate at 90 mg (2.1-3.3 mg/kg) equivalent to 67.5 mg codeine base (1.6-2.5 mg/kg). The geometric mean maximum plasma concentrations of acetaminophen, codeine, and codeine-6-glucuronide were 7.95 μg/mL, 11.0 ng/mL, and 3819 ng/mL, respectively. Morphine concentrations were <1 ng/mL. The terminal half-lives of acetaminophen, codeine, and codeine-6-glucuronide were 0.94, 1.71, and 3.12 h. There were no significant changes in vF thresholds, except at 12 h which decreased on average by 17% compared to baseline. The decrease in vF thresholds at 12 h could be due to aversion, hyperalgesia, or random variability. The lack of antinociception in this study could be due to a true lack of antinociception, lack of model sensitivity, or specificity. Further studies using different models (including clinical trials), different dog breeds, multiple dose regimens, and a range of dosages are needed prior to recommended use or concluding lack of efficacy for oral acetaminophen/codeine in dogs.
authors.affiliation: Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.
authors.forename: B
authors.initials: B
authors.lastname: KuKanich
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D003061:Codeine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D004285:Dogs / Q000378:metabolism; D004338:Drug Combinations; D010146:Pain / Q000188:drug therapy
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D004338:Drug Combinations; D000082:Acetaminophen; C061773:codeine-6-glucuronide; D003061:Codeine