Pharmacokinetics and safety of repeated oral dosing of acetaminophen in adult horses.

Abstract

There are no published studies on the pharmacokinetics of acetaminophen at the dosage used clinically (20mg/kg), nor has the safety of multiple doses in horses been investigated. Define the pharmacokinetic parameters of oral acetaminophen at 20mg/kg in adult horses as a single dose, and twice daily for 14days to assess the safety of multiple dosing. Pharmacokinetic study, multiple dose safety study. Eight healthy Thoroughbred geldings were given acetaminophen (20mg/kg; 500mg tablets) orally as a single dose followed by doses every 12h for 14days. Serial blood samples were collected for determination of plasma acetaminophen concentrations using high performance liquid chromatography with ultraviolet detection. Serum biochemical analysis, gastroscopy and liver biopsy were examined during the safety study. Following a single dose, mean maximum concentration (Cmax ) was 16.61μg/mL at 1.35h (Tmax ), and drug concentration was below the lower limit of detection in most horses by 24h. Elimination half-life (T1/2 ) was 2.78h. No significant accumulation was noted following multiple doses. Average Cmax of acetaminophen following multiple oral dosing was 15.85μg/mL, with a Tmax of 0.99h and T1/2 of 4h. Serum activities of sorbitol dehydrogenase were significantly decreased and total bilirubin concentrations were significantly increased following the last dose. No statistically significant changes were noted in gastroscopy scores. Only one dose level (20mg/kg) was studied, sample size was small and only a single breed and sex was used, with no pretreatment liver biopsies. This study described the pharmacokinetics of acetaminophen following single and multiple 20mg/kg oral doses in adult horses and demonstrated the safety of acetaminophen with multiple oral dosing over 14days. The summary is available in Portuguese - see Supporting information.