Pharmacokinetics of Acetaminophen and Metabolites after Rectal, Oral and Intravenous Single-Dose Administration in Healthy Adult Horses.

Abstract

Acetaminophen is increasingly used in critically ill horses, but gastrointestinal disease may limit oral administration. There are currently no pharmacokinetic data in horses for acetaminophen (APAP) via alternative routes such as rectal administration. This study described and compared plasma pharmacokinetics of APAP, APAP-glucuronide and APAP-sulfate) after single rectal, oral and intravenous administration to adult horses using a randomized crossover design. Plasma APAP and metabolites were quantified by LC-MS/MS and subject to pharmacokinetic analysis. Rectal administration produced lower systemic exposure than oral administration, with significant differences on maximal plasma concentrations (Cmax 5.28 ± 2.62 vs. 22.62 ± 5.80 μg/mL), area under the curve (AUC 16.91 ± 9.69 vs. 89.76 ± 11.65 μg·h/mL), and bioavailability (15.38 ± 8.27% vs. 82.35 ± 22.64%). In all routes, APAP-sulfate AUC exceeded that of APAP-glucuronide. Despite lower bioavailability, rectal administration was well tolerated and achieved plasma concentrations close to extrapolated therapeutic ranges, supporting its potential clinical applicability.