Pharmacokinetics of single dose administration of three increasing doses of acetaminophen per os in 1-3-month-old foals.

Abstract

Acetaminophen is a common analgesic and antipyretic drug used in human medicine and might be an alternative to nonsteroidal anti-inflammatory drugs for treating pain and pyrexia in foals. The pharmacokinetics and safety of differing doses of acetaminophen have not been investigated in foals. To determine the plasma pharmacokinetics and any changes in haematology and biochemistry profiles following oral administration of single doses of acetaminophen at 10, 20, and 40 mg/kg to foals. Randomised cross-over pharmacokinetic study. Six Quarter Horse (two colts and four fillies) foals received 10, 20, and 40 mg/kg acetaminophen orally once. Haematology and biochemistry profiles were performed before and 7 days after each drug administration. Blood samples were collected over 64 h after drug administration and were used to quantify plasma acetaminophen concentrations by liquid chromatography. Pharmacokinetic parameters were determined using compartmental analysis. Median (range) acetaminophen plasma concentrations were 4.4 (1.8-5.1), 6.3 (2.6-12.6), and 14 (7.3-18)μg/ml for the 10, 20, and 40 mg/kg doses, respectively. Median acetaminophen area under the concentration versus time curve (AUC)0-∞ ranged from 25 (11-32), 41 (22-74), and 105 (82-142)h × μg/ml for the 10, 20, and 40 mg/kg doses, respectively. Dose-normalised maximal concentrations and AUC0-∞ values were similar across dose concentrations (p > 0.05). Median terminal half-life for all doses was 2.7-2.8h. Haematology and biochemistry profiles were normal except for blood urea nitrogen and alkaline phosphatase concentrations. Foals were growing throughout the study, starting at 1month and ending at 3months. Deposition of drugs changes with age. The sample size was small and only single doses were evaluated. No liver biopsies were performed. Plasma disposition of acetaminophen after a single oral dose of 10, 20, and 40 mg/kg to 1-3-month-old foals varies greatly with the dose. The analgesic and antipyretic effect in foals is unknown.