Related Experiment Videos
Pharmacokinetics of gentamicin in newborn to 30-day-old foals
L E Cummings1, A J Guthrie, J D Harkins
1Department of Veterinary Physiology, Pharmacology, and Toxicology, School of Veterinary Medicine, Louisiana State University, Baton Rouge 70803.
Insights
Gentamicin elimination in foals improves with age, reaching adult levels by 30 days. However, foals show higher volume of distribution (Vd) than adult horses, indicating differences in drug distribution.
Area of Science:
- Pharmacokinetics and Pharmacodynamics
- Veterinary Medicine
- Neonatal Animal Physiology
Background:
- Gentamicin is a crucial antibiotic for treating bacterial infections in foals.
- Understanding gentamicin pharmacokinetics in neonatal foals is vital for effective and safe therapeutic use.
- Age-related changes in drug metabolism and distribution can significantly impact treatment outcomes.
Purpose of the Study:
- To characterize the pharmacokinetic profile of gentamicin in Thoroughbred foals.
- To investigate age-dependent changes in gentamicin disposition from birth to 30 days of age.
- To compare gentamicin pharmacokinetics between foals and adult mares.
Main Methods:
- Intravenous administration of gentamicin sulfate (4 mg/kg) to 6 Thoroughbred foals on days 1, 5, 10, 15, and 30 postpartum.
- Administration of gentamicin to mares on day 40 postpartum for comparison.
- Analysis of serum gentamicin concentrations using a two-compartment model to determine pharmacokinetic parameters (elimination rate constant, volume of distribution, total body clearance).
Main Results:
- The overall elimination rate constant in foals increased significantly with age, reaching adult levels by 30 days.
- The volume of distribution (Vd) in foals was significantly higher than in mares, particularly at 5 and 10 days of age.
- Total body clearance (ClB) of gentamicin in foals increased with age and approached adult levels by day 30, with lower ClB observed on day 1 and day 15 compared to day 30.
Conclusions:
- Gentamicin pharmacokinetics in foals mature significantly between birth and 30 days of age.
- Higher Vd in foals suggests differences in drug distribution compared to adult horses.
- These findings are critical for optimizing gentamicin dosing regimens in neonatal foals to ensure therapeutic efficacy and minimize toxicity.
Abstract:
Gentamicin sulfate, equivalent to 4 mg of gentamicin base/kg of body weight, was administered IV to 6 Thoroughbred foals on day 1 (12 to 24 hours of age) and at 5, 10, 15, and 30 days after birth. On day 40 after parturition, gentamicin was given to the mares at a dosage similar to that used in foals. Decay of serum gentamicin concentrations was best described by a 2-compartment model. Among foals, the overall elimination rate constant at 30 days of age was significantly (P less than 0.05) greater than at days 1, 10, and 15. There was, however, no difference in the overall elimination rate constant between foals and mares. The volume of distribution (Vd), determined on the basis of total area under the disposition curve, did not change between day 1 and day 30. Mean values of Vd of foals were between 1.5 and 2.5 times higher than the mean Vd of the mares; however, only values from the foals at days 5 and 10 were significantly greater. Both age and interindividual differences were reflected in the total body clearance (ClB) of gentamicin. Total body clearance of gentamicin of foals on day 1 was less than that of foals on days 5, 10, and 30. Additionally, C1B of gentamicin on day 15 was less than that on day 30. There was no significant difference between ClB of foals and mares except for the day-30 group, which had a higher clearance rate than did the adults. Protein binding of gentamicin was less than 30% in all groups, and there were no apparent age-related differences.