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.

Bioavailability of suppository acetaminophen in healthy and hospitalized ill dogs

“…In humans, antinociception is reported at plasma APAP levels of 4 μg/ml or greater (Pickering et al., ). Antinociception was not detected with use of an electronic von Frey device with APAP C MAX of 7.95 μg/ml in Greyhounds (KuKanich, ) when administered with codeine. Given the low bioavailability of suppository APAP and antinociception evidence, it is doubtful that suppository APAP at current dosages is of clinical benefit.…”

Clinical evaluation of postoperative analgesia and serum biochemical changes of paracetamol compared to meloxicam and carprofen in bitches undergoing ovariohysterectomy

“…It would be interesting to evaluate the analgesic effects of paracetamol following orthopaedic surgery, for example, or for the treatment of chronic pain. Similarly, further investigation of long-term treatments using different doses of paracetamol may be valuable, as the existing veterinary literature suggests large dose ranges (e.g., between 0.2-10 and 1-25 mg kg -1 , administered intravenously and orally, respectively) [64–66]. A further limitation is that plasma concentrations of paracetamol, meloxicam, and carprofen were not evaluated in the present study.…”

Pharmacogenetics of opioid analgesics in dogs

“…This combination (tylenol-codeine No. 3) has been popular in people to relieve mild to moderate pain (Kukanich, 2016).…”

“…This combination (tylenol—codeine No. 3) has been popular in people to relieve mild to moderate pain (Kukanich, ). A negligible concentration of morphine but substantial amounts of codeine‐6‐G has been detected in the plasma of the study dogs after oral codeine administration (Findlay et al., ; Kukanich, , ).…”

“…3) has been popular in people to relieve mild to moderate pain (Kukanich, ). A negligible concentration of morphine but substantial amounts of codeine‐6‐G has been detected in the plasma of the study dogs after oral codeine administration (Findlay et al., ; Kukanich, , ). In addition to poor oral bioavailability, formation of low amounts of morphine, as seen in CYP2D6 poor metabolizers (Kirchheiner, Keulen, Bauer, & Brockmöller, ), could be attributed to lack of antinociceptive efficacy of codeine in these study (greyhound) dogs.…”