Pharmacokinetics of metronidazole in foals: influence of age within the neonatal period.
Abstract: Neonatal foals have unique pharmacokinetics, which may lead to accumulation of certain drugs when adult horse dosage regimens are used. Given its lipophilic nature and requirement for hepatic metabolism, metronidazole may be one of these drugs. The purpose of this study was to determine the pharmacokinetic profiles of metronidazole in twelve healthy foals at 1-2.5 days of age when administered as a single intravenous (IV) and intragastric (IG) dose of 15 mg/kg. Foals in the intravenous group were studied a second time at 10-12 days of age to evaluate the influence of age on pharmacokinetics within the neonatal period. Blood samples were collected at serial time points after metronidazole administration. Metronidazole concentration in plasma was measured using LC-MS. Pharmacokinetic parameters were determined using noncompartmental analysis and compared between age groups. At 1-2.5 days of age, the mean peak plasma concentration after IV infusion was 18.79 ± 1.46 μg/mL, elimination half-life was 11.8 ± 1.77 h, clearance was 0.84 ± 0.13 mL/min/kg and the volume of distribution (steady-state) was 0.87 ± 0.07 L/kg. At 10-12 days of age, the mean peak plasma concentration after IV infusion was 18.17 ± 1.42 μg/mL, elimination half-life was 9.07 ± 2.84 h, clearance was 1.14 ± 0.21 mL/min/kg and the volume of distribution (steady-state) was 0.88 ± 0.06 L/kg. Oral approximated bioavailability was 100%. Cmax and Tmax after oral dosing were 14.85 ± 0.54 μg/mL and 1.75 (1-4) h, respectively. The elimination half-life was longer and clearance was reduced in neonatal foals at 1-2.5 days as compared to 10-12 days of age (P = 0.006, P = 0.001, respectively). This study warrants consideration for altered dosing recommendations in foals, especially a longer interval (12 h).
© 2014 John Wiley & Sons Ltd.
Publication Date: 2014-10-01 PubMed ID: 25271172DOI: 10.1111/jvp.12164Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research studied how a drug called metronidazole works in the bodies of newborn foals (young horses), and found that the drug behaves differently in very young foals compared to slightly older foals. Based on these results, the authors suggest modifying the recommended dose of the drug for newborn horses.
Research Purpose and Methodology
- The primary goal of the research was to understand how metronidazole behaves inside the body of neonatal foals, including how quickly it is eliminated. This is important because metronidazole is lipophilic (it dissolves easily in fats and oils), and requires the liver to break down and remove. Therefore, its use in young foals can potentially lead to the accumulation of the drug in the body when the prescribed dosage meant for adult horses is used.
- The drug was administered to 12 healthy foals at an age of 1-2.5 days through two methods—a single dose given intravenously (IV) and a single dose given intragastrically (IG), both with a strength of 15 mg/kg.
- To study the influence of age on the pharmacokinetics of the drug, the foals that received the drug intravenously were studied again at an age of 10-12 days.
- Blood samples were collected at numerous time points after administering the drug to measure the concentration of metronidazole in plasma. These measurements were done using a method known as LC-MS, or liquid chromatography-mass spectrometry.
Key Findings and Recommendations
- The key findings of the study revealed differences in several pharmacokinetic parameters, like elimination half-life (the time it takes for the body to eliminate half the amount of the drug) and clearance (the rate at which the drug is removed from the body) among young and older neonatal foals. Specifically, at an age of 1-2.5 days the elimination half-life was longer, and clearance was lower as compared to the foals at an age of 10-12 days.
- According to these results, the foals at the age of 1-2.5 days are keeping the drug in their bodies for longer periods than the older foals, which demonstrates that age affects how quickly the drug is broken down and removed.
- Based on these findings, the study recommends adjusting the dosing recommendations for metronidazole in foals, particularly suggesting a longer interval (12 hours) between doses. This is to avoid any adverse health effects due to the accumulation of the drug in the body of very young foals.
Cite This Article
APA
Swain EA, Magdesian KG, Kass PH, Edman JE, Knych HK.
(2014).
Pharmacokinetics of metronidazole in foals: influence of age within the neonatal period.
J Vet Pharmacol Ther, 38(3), 227-234.
https://doi.org/10.1111/jvp.12164 Publication
Researcher Affiliations
- William R. Pritchard Veterinary Medical Teaching Hospital, University of California, Davis, CA, USA.
MeSH Terms
- Age Factors
- Animals
- Animals, Newborn / metabolism
- Anti-Bacterial Agents / blood
- Anti-Bacterial Agents / pharmacokinetics
- Female
- Half-Life
- Horses / metabolism
- Injections, Intravenous / veterinary
- Intubation, Gastrointestinal / veterinary
- Male
- Metronidazole / administration & dosage
- Metronidazole / blood
- Metronidazole / pharmacokinetics
Citations
This article has been cited 2 times.- Kir F, Jusko WJ. Metronidazole Pharmacokinetics Across Species: Meta-Analysis Integrating Allometric Scaling and Minimal Physiologically-Based Pharmacokinetic Modeling. AAPS J 2025 Dec 5;28(1):25.
- Mendoza FJ, Toribio RE. An Overview of Donkey Neonatology. Animals (Basel) 2025 Jul 6;15(13).
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