Comparative pharmacokinetics and a clinical laboratory evaluation of intravenous acetaminophen in Beagle and Galgo Español dogs

Abstract

Objective: To assess the pharmacokinetics (PK) and conduct a clinical laboratory evaluation of acetaminophen in Beagle and Galgo Español (GE) dogs.

Study design: Prospective randomized experimental trial.

Animals: A total of 20 healthy dogs - 10 Beagles and 10 GE (six males and four females in both groups).

Methods: Acetaminophen (10 and 20 mg kg^-1) was administered intravenously (IV) to the dogs on two different occasions. Plasma concentrations were analysed by high-performance liquid chromatography. PK analysis was undertaken using compartmental modelling with ADAPT 5 software. Simulations after multiple IV doses were investigated. Clinical laboratory values such as red blood cell (RBC) count, haemoglobin (Hb), haematocrit (Ht), white blood cell (WBC) count, platelet count, total proteins, alanine aminotransferase (ALT), aspartate aminotransferase, urea and creatinine were measured before and 24 hours after acetaminophen administration in combination with clinical examination to assess side effects resulting from the drug.

Results: A two-compartmental model best described time-concentration profiles of acetaminophen. PK parameters were different as a result of a breed effect. For doses of 10 and 20 mg kg^-1, respectively, clearance values were 1.70 (1.15-2.27) and 1.62 (1.06-2.86) L kg^-1 hour^-1 for Beagles and 1.18 (0.70-1.39) and 1.08 (0.67-1.35) L kg^-1 hour^-1 for GE; elimination half-life values were 2.64 (0.52-4.46) and 2.86 (0.87-4.63) hours for Beagles and 3.49 (1.89-7.80) and 4.57 (2.08-8.90) hours for GE. Significant differences were also found between GE and Beagles in the RBC count, Ht, Hb, WBC count and serum ALT before drug administration, and these differences were maintained 24 hours later, independent of the dosage used. For each breed, no side effects resulting from IV acetaminophen administration were observed at doses of either 10 or 20 mg kg^-1.

Conclusions and clinical relevance: IV PK of acetaminophen was different between Beagles and GE dogs. Side effects were not detected. Further studies are necessary to evaluate the PK in a clinical context.

Keywords: Beagles; Galgo Español; acetaminophen; clinical laboratory values; pharmacokinetics.