Influence of general anaesthesia on the intravenous acetaminophen pharmacokinetics in Beagle dogs

Abstract

Objective: To determine if general anaesthesia influences the intravenous (IV) pharmacokinetics (PK) of acetaminophen in dogs.

Study design: Prospective, crossover, randomized experimental study.

Animals: A group of nine healthy Beagle dogs.

Methods: Acetaminophen PK were determined in conscious and anaesthetized dogs on two separate occasions. Blood samples were collected before, and at 5, 10, 15, 30, 45, 60 and 90 minutes and 2, 3, 4, 6, 8, 12 and 24 hours after 20 mg kg^-1 IV acetaminophen administration. Haematocrit, total proteins, albumin, alanine aminotransferase, aspartate aminotransferase, urea and creatinine were determined at baseline and 24 hours after acetaminophen. The anaesthetized group underwent general anaesthesia (90 minutes) for dental cleaning. After the administration of dexmedetomidine (3 μg kg^-1) intramuscularly, anaesthesia was induced with propofol (2-3 mg kg^-1) IV, followed by acetaminophen administration. Anaesthesia was maintained with isoflurane in 50% oxygen (Fe'Iso 1.3-1.5%). Dogs were mechanically ventilated. Plasma concentrations were analysed with high-performance liquid chromatography. PK analysis was undertaken using compartmental modelling. A Wilcoxon test was used to compare PK data between groups, and clinical laboratory values between groups, and before versus 24 hours after acetaminophen administration. Data are presented as median and range (p < 0.05).

Results: A two-compartmental model best described time-concentration profiles of acetaminophen. No significant differences were found for volume of distribution values 1.41 (0.94-3.65) and 1.72 (0.89-2.60) L kg^-1, clearance values 1.52 (0.71-2.30) and 1.60 (0.91-1.78) L kg^-1 hour^-1 or terminal elimination half-life values 2.45 (1.45-8.71) and 3.57 (1.96-6.35) hours between conscious and anaesthetized dogs, respectively. Clinical laboratory variables were within normal range. No adverse effects were recorded.

Conclusions and clinical relevance: IV acetaminophen PK in healthy Beagle dogs were unaffected by general anaesthesia under the study conditions. Further studies are necessary to evaluate the PK in different clinical contexts.

Keywords: Beagles; acetaminophen; anaesthesia; clinical laboratory variables; isoflurane; pharmacokinetics.