Pharmacokinetics of acetaminophen after intravenous and oral administration in fasted and fed Labrador Retriever dogs

Abstract

Acetaminophen (paracetamol) is used in dogs to manage fever and mild pain. The aim of this study was to assess the pharmacokinetics of acetaminophen in both fed and fasted Labrador Retrievers after a single intravenous and oral administration (20 mg/kg). Six healthy dogs underwent three treatments in a randomized block study (a,n = 2; b,n = 2; c,n = 2). In phase one, group a received acetaminophen intravenously, group b and c orally after being fasted and fed, respectively. In phase two and three, groups were swapped, and the experiment was repeated. At the end of the trial, each dog received the same treatment. Acetaminophen plasma concentrations were detected using a validated HPLC‐UV method. The pharmacokinetic analysis was performed using a noncompartmental model. Clearance, volume at steady state and half‐life of acetaminophen in Labrador Retrievers were 0.42 L/kg hr, 0.87 L/kg and 1.35 hr, respectively. No significant statistical differences were found between fasted and fed dogs regarding maximum plasma concentration, time at maximum concentration and bioavailability as measured by the AUC. Feeding does not significantly affect the acetaminophen oral pharmacokinetics.

Effects of Acetaminophen or Ibuprofen Monotherapy in Febrile Children: A Meta-Analysis of Randomized Controlled Trials

“…Out of twenty-four included studies with the oral route of medication, there was only one study with the intravenous route of acetaminophen and one study with the rectal or oral route of acetaminophen and intravenous route of ibuprofen. There was a difference in pharmacokinetics when the administration route was different, which might have led to the variation of time-related antipyretic efficacy [ 52 , 53 ]. Nevertheless, there was no outcome difference when these two studies with different routes of medication were weeded out from the analysis.…”

Paracetamol: A Focus on Dogs

“…The clearance of APAP in dogs ranged from 0.42 L/h/kg (Sartini et al, 2021) to 1.74 L/h/kg (Neirinckx et al, 2010). The clearance was slower in Labrador retriever dogs compared to that found in Beagles, Greyhounds and Galgo Español dogs (Kukanich, 2010;Neirinckx et al, 2010;Koyanagi et al, 2014;Serrano-Rodríguez et al, 2019).…”

“…Consequently, the oral bioavailability differences reported in dogs (Neirinckx et al, 2010 44%;Koyanagi et al, 2014 100%) might be assumed to be due to diverse metabolisms in canine breeds (1st pass and glucuronidation) (Bock et al, 2002). A recent study (Sartini et al, 2021), in line with the human findings, affirmed that no statistically significant differences were found between fasted and fed dogs regarding bioavailability, Cmax and Tmax, thus feeding did not significantly affect the APAP absorption process neither its PK.…”

“…Further evidencing its potential for post-surgical use, the administration of the recommended dose of APAP in dogs (20 mg/kg every 8 h) (Sartini et al, 2021) can be used instead of NSAIDs, especially if these are contraindicated (Berry, 2015). To note that recently, a recommended drug combination suggested for analgesia in dogs, is an oral opioid formulation plus APAP (Plumb, 2015;Muir, 2015).…”

Erratum

“…In the article by Sartini et al (2021), Figures 2 and 3 were wrongly swapped in the published version. The correct figures are presented below.…”