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

Abstract

Background: 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. Objectives: 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. Study design: Randomised cross-over pharmacokinetic study. Methods: 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. Results: 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 2.7–2.8 h. Haematology and biochemistry profiles were normal except for blood urea nitrogen and alkaline phosphatase concentrations. Main limitations: Foals were growing throughout the study, starting at 1 month and ending at 3 months. Deposition of drugs changes with age. The sample size was small and only single doses were evaluated. No liver biopsies were performed. Conclusion: 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.