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



Background:

Acetaminophen is a common analgesic and antipyretic drug used in human medicine and might be an alternative to non-steroidal 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 (2 colts, 4 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 hours 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) ug/ml for the 10, 20, and 40 mg/kg doses, respectively. Median acetaminophen area under the concentration vs. time curve (AUC)0-∞ ranged from 25(11-32), 41(22-74), and 105 (82-142)h*ug/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 to 2.8 hours. Haematology and biochemistry profiles were normal except for BUN and alkaline phosphatase concentrations.


Main limitations:

Foals were growing throughout study, starting at 1 month and ending at 3 months. Deposition of drugs change 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 anti-pyretic effect in foals is unknown.


Keywords:

acetaminophen; foal; horse; plasma disposition; safety.



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