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Updated: Jul 22, 2025
An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
Pharmacokinetics of multiple oral doses of acetaminophen in equine neonates
Cosette Faivre1, David M Wong1, Nicolas F Villarino2
1Department of Veterinary Clinical Sciences, Iowa State University, Ames, IA.
Insights
Neonatal foals tolerated oral acetaminophen well at both tested dosages. Further studies are needed to establish optimal acetaminophen dosing for pain and fever relief in foals.
Area of Science:
- Veterinary Pharmacology
- Equine Medicine
- Drug Pharmacokinetics
Background:
- Acetaminophen (APAP) is a common analgesic and antipyretic.
- Limited pharmacokinetic data exists for oral APAP in neonatal foals.
- Understanding APAP disposition is crucial for safe and effective therapeutic use in foals.
Purpose of the Study:
- To evaluate the pharmacokinetics and clinical safety of oral acetaminophen in neonatal foals.
- To compare two dosing regimens: 40 mg/kg every 12 hours (q12h) versus 60 mg/kg every 24 hours (q24h).
- To assess safety over a 14-day administration period.
Main Methods:
- Twelve healthy neonatal foals were divided into two groups (n=6 each).
- Foals received either 40 mg/kg q12h or 60 mg/kg q24h acetaminophen for 14 days.
- Plasma acetaminophen concentrations were measured using HPLC; pharmacokinetic parameters were calculated via non-compartmental analysis. Hematology and biochemistry were monitored.
Main Results:
- No significant changes in hematology or biochemistry profiles were observed.
- Mild elevations in liver enzymes (GGT, SDH) were noted in some foals.
- The 60 mg/kg q24h dose yielded a higher median Cmax (28 μg/mL) compared to 40 mg/kg q12h (23 μg/mL).
- Area under the curve (AUC0-8h) was greater for the 60 mg/kg dose (128 h•µg/mL) than the 40 mg/kg dose (100 h•µg/mL).
- Trough plasma concentrations decreased over time for both regimens.
Conclusions:
- Neonatal foals demonstrate good tolerance to oral acetaminophen at both 40 mg/kg q12h and 60 mg/kg q24h.
- These findings support the potential use of oral acetaminophen in foals.
- Further research is recommended to determine optimal analgesic and antipyretic dosage regimens for foals.
Objective:
To determine the pharmacokinetics and clinical safety of acetaminophen after oral administration of 40 mg/kg q 12 hours or 60 mg/kg q 24 hours for 14 days.
Animals:
12 healthy light-breed neonatal foals.
Procedures:
6 foals received acetaminophen at 40 mg/kg q 12 hours and 6 foals received 60 mg/kg q 24 hours for 14 days. The study dates were January 31 to April 15, 2023. Physical examinations were performed daily. Plasma disposition of acetaminophen was determined after the first, mid-point drug administration. Hematology and biochemistry analysis was performed before the study, day 7, and the last day of drug administration. Plasma acetaminophen concentrations were determined by high-performance liquid chromatography. Plasma pharmacokinetic parameters were estimated using noncompartmental analysis.
Results:
No statistically significant changes occurred on hematology or biochemistry profiles. Elevations in γ-glutamyl transferase (GGT) and sorbitol dehydrogenase (SDH) were noted in 4 foals at various time points. The maximum plasma concentration (Cmax) occurred within 2 hours for both doses. The 60 mg/kg dose resulted in a larger median Cmax (range) at 28 μg/mL (22-32) than the 40 mg/kg dose at 23 μg/mL (19-27). The median area under the concentration-vs-time curve from 0 to 8 hours (AUC0-8 hour [range]) was 100 h•µg/mL (82-100) at 40 mg/kg and 128 h•µg/mL (120-168) for 60 mg/kg. Trough concentrations decreased over time for both regimens.
Clinical Relevance:
Foals tolerate oral acetaminophen at 40 mg/kg q 12 hours or 60 mg/kg q 24 hours. Further analgesic and antipyretic studies will help to delineate optimal dosage regimens of acetaminophen to treat foals.
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