Pharmacokinetics of single-dose oral acetaminophen with and without concurrent administration of silymarin or N-acetylcysteine in orange-winged Amazon parrots (Amazona amazonica).

OBJECTIVE

To determine the pharmacokinetics of acetaminophen (N-acetyl-para-aminophenol [APAP]) and its metabolites after oral administration of a single dose of APAP, with or without silymarin or N-acetylcysteine (NAC), to orange-winged Amazon parrots (Amazona amazonica).

METHODS

Eight parrots received, in 3 separate studies, 1 of the following oral treatments: (1) APAP (100 mg/kg) with silymarin (50 mg/kg, twice, q 12 h); (2) APAP (100 mg/kg) with NAC (400 mg/kg); or (3) APAP (100 mg/kg) alone. For each study, blood samples were collected over 24 hours after drug administration to evaluate plasma concentrations of APAP, APAP-glucuronide, and APAP-sulfate. Pharmacokinetic parameters were calculated. Plasma biochemistry panels were performed before and after each study. In a fourth study, a single oral dose of APAP (100 mg/kg) was administered to 8 additional parrots for adverse effects evaluation alone.

RESULTS

Pharmacokinetic parameters for APAP, APAP-glucuronide, and APAP-sulfate were established. The APAP maximum plasma concentration, time of maximal plasma concentration, and half-life across studies ranged from 2,016.9 to 2,917.2 ng/mL, 1.13 to 2.1 hours, and 1.3 to 1.45 hours, respectively. Acetaminophen had marked metabolism to APAP-glucuronide and negligible to APAP-sulfate. Concurrent administration of APAP with silymarin resulted in a mild but significant elevation in glutamate dehydrogenase.

CONCLUSIONS

Acetaminophen plasma concentrations were lower than in other avian species despite a relatively high dose. Acetaminophen has fast absorption, short half-life, and marked glucuronidation. Single oral dose administration of APAP, alone or with NAC, appears safe based on plasma biochemistries. Multidose and pharmacodynamic studies are needed.

CLINICAL RELEVANCE

This is the first pharmacokinetic study of APAP in psittacines, which has the potential to be an effective and safe component of multimodal analgesia in these species.