Background: There are currently no pharmacokinetic data in horses on acetaminophen (APAP) or its metabolites following rectal administration, an alternative route when gastrointestinal dysfunction limits oral dosing.
Objective: To describe and compare plasma pharmacokinetics of APAP and its metabolites (APAP-glucuronide and APAP-sulfate) after single rectal and oral administration to adult horses.
Animals: Six healthy university-owned adult geldings.
Methods: Horses received APAP rectally (30 mg/kg), orally (30 mg/kg), and intravenously (10 mg/kg) in a randomized crossover design. Plasma APAP and metabolites were quantified by LC-MS/MS after validation and subject to noncompartmental analysis (Phoenix-WinNonlin).
Results: Rectal administration resulted in lower maximum plasma concentration (Cmax = 5.28 ± 2.62 µg/mL), area under the concentration-time curve (AUC = 16.91 ± 9.69 µg·h/mL), and bioavailability (F = 15.38 ± 8.27 %) compared to the oral route (Cmax = 22.62 ± 5.80 µg/mL, AUC = 89.76 ± 11.65 µg·h/mL, and F = 82.35 ± 22.64 % . In all routes, APAP-sulfate AUC (rectal = 29.14 ± 12.87; oral = 113.10 ± 31.59 µg·h/mL) exceeded that of APAP-glucuronide (rectal = 16.32 ± 12.28; oral = 74.99 ± 35.80 µg·h/mL). For each metabolite, metabolic ratios (AUC metabolite/AUC APAP) were similar after oral, rectal, and intravenous administration.
Conclusions: Rectal administration achieved extrapolated therapeutic levels comparable to humans (5–20 µg/mL), despite lower bioavailability than oral dosing. In contrast to humans, sulfation appears to be the predominant pathway for biotransformation in horses. Similar metabolic ratios were obtained across administration routes.
