Pharmacokinetics of multiple oral doses of acetaminophen in equine neonates.

The study looks at how neonatal foals’ body processes acetaminophen administered orally at two different dosage regimens for 14 days, and assesses its clinical safety. The results suggest that foals can tolerate these dosages well, with no significant changes seen in their blood workup or biochemistry profiles.

Research Methodology

• The study was conducted on 12 healthy light-breed neonatal foals. Each foal was given two different dosages of acetaminophen: 6 received 40 mg/kg every 12 hours and the other 6 received 60 mg/kg every 24 hours, for a total duration of 14 days.
• The study was carried out between January 31 and April 15, 2023. Daily physical examinations were performed on all the foals.
• The concentrations of acetaminophen in the plasma were measured after the first and mid-point drug administrations, using high-performance liquid chromatography.
• Blood work and biochemistry analysis was carried out before commencement of the study, on the 7th day, and on the last day of drug administration.
• The pharmacokinetic parameters of the drug in the body (how it is absorbed, distributed, metabolized and expelled) were determined using a noncompartmental analysis approach.

Findings

• No significant changes were observed in the profiles generated from hematology or biochemical analysis. This indicates that the acetaminophen doses administered did not lead to any significant alterations in the biochemical or hematological functions of the foals.
• However, there were observed elevations in enzymatic activity, specifically γ-glutamyl transferase (GGT) and sorbitol dehydrogenase (SDH), in 4 foals at various points during the study..
• The maximum concentration (Cmax) of acetaminophen in the plasma occurred within 2 hours for both doses.
• The 60 mg/kg dosage produced a higher median Cmax of 28 μg/mL compared to 23 μg/mL with the 40 mg/kg dose.
• The median area under the concentration-vs-time curve from 0 to 8 hours (AUC0-8 hour), which is a measure of the overall drug exposure, was higher for the 60 mg/kg dosage.
• The trough concentrations, which are the lowest concentration levels in the bloodstream, decreased over time for both regimens.

Conclusions

• The study found that neonatal foals are able to tolerate oral administration of acetaminophen, with the two dosage regimens used in the study not resulting in any significant adverse effects observable through hematology or biochemistry profiles.
• However, it is recommended that further studies be conducted to explore the pain-relieving and fever-reducing effects of acetaminophen in foals to propose optimal dosage regimens.