Species dependent gentamicin pharmacokinetics and nephrotoxicity in the young horse.
Abstract: Gentamicin pharmacokinetics and nephrotoxic potential were evaluated in twelve 2 to 3 month-old horses. Whereas recent evidence in our clinic indicated that young horses may be especially susceptible to gentamicin nephrotoxicity, young rabbits and rats are usually resistant. Gentamicin (4.5 mg/kg) was given by rapid intravenous injection. Serum gentamicin concentrations over a 13-hour period were fitted to an open, two-compartment, pharmacokinetic model. Subsequently, the same horses were divided into groups of 3 horses each. Each group received 0, 2.2, 4.4 or 8.8 mg gentamicin/kg, intramuscularly, every 12 hours for 15 days. Renal function was monitored. Peak and trough gentamicin concentrations were monitored daily. Renal sections were collected for histopathologic and electron microscopic examination. The (mean +/- SD) serum halflife was 194 +/- 37 minutes, total body clearance (ClB) was 1.65 +/- 0.79 mL/min/kg and volume of distribution at steady state (Vd(ss)) was 30.6 +/- 9.4 L/100 kg. Decreased renal function, as detected by elevated serum urea nitrogen or creatinine concentrations, was detected only in the two youngest foals (including animals in both the 4.4 and 8.8 mg/kg dose groups). The trough serum gentamicin concentrations of these 2 horses increased over time. These horses had the lowest ClB and Vd(ss) in the intravenous study. Morphologic changes were seen in kidneys of all treated horses and were similar to those occurring with gentamicin toxicity in other species. Our results support the clinical impression that very young horses may be more susceptible than adult horses, and adults of other species, to gentamicin nephrotoxicity.
Publication Date: 1983-09-01 PubMed ID: 6642102DOI: 10.1016/s0272-0590(83)80020-7Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study investigates how young horses process gentamicin, a type of antibiotic, and measures its potential damaging effects on their kidneys. It suggests that young horses may be more prone to kidney damage from the drug than adults or individuals of other species.
Research Method
- The researchers observed the effects of gentamicin on twelve horses aged 2 to 3 months in order to determine the drug’s pharmacokinetics (how it is processed by the body) and nephrotoxicity (its potential to damage kidneys).
- The drug was first given to the horses as a rapid intravenous injection and its concentration in the bloodstream over the next 13 hours was monitored and fitted to a pharmacokinetic model.
- Following this, the horses were split into groups of three and given varying doses of gentamicin intramuscularly twice a day for 15 days. One group received no gentamicin as a control.
- The researchers monitored several metrics throughout this experiment to check for signs of kidney damage. This included testing for increased levels of serum urea nitrogen or creatinine in the bloodstream, substances that are usually filtered out by healthy kidneys.
- After completing the course of gentamicin, kidneys were removed from all test subjects and examined for histopathological and electron microscopic changes indicative of gentamicin-induced kidney damage.
Findings
- Gentamicin showed a mean serum half-life of around 194 minutes in the young horses. Its total body clearance rate was determined to be 1.65 mL/min/kg and it had a volume of distribution at steady state of 30.6 L/100 kg.
- Signs of decreased kidney function were primarily observed in the youngest test subjects. This included cases where serum urea nitrogen or creatinine levels were measurably elevated.
- The lowest clearance rates and volumes of distribution at steady state were seen in those horses that exhibited a rise in serum gentamicin concentrations over time, potentially indicative of the damaging effects of the drug on renal function.
- Post-mortem examination of the kidneys showed changes consistent with those seen in cases of gentamicin toxicity in other creatures.
Implications
- The results suggest that very young horses could be more susceptible to kidney damage caused by gentamicin than their adult counterparts or individuals of other species.
- This insight might impact guidelines or recommendations for gentamicin usage in young equine therapy, protecting the subjects from potential harm and saving the veterinary community resources spent on treating negative side-effects of the drug.
Cite This Article
APA
Riviere JE, Coppoc GL, Hinsman EJ, Carlton WW, Traver DS.
(1983).
Species dependent gentamicin pharmacokinetics and nephrotoxicity in the young horse.
Fundam Appl Toxicol, 3(5), 448-457.
https://doi.org/10.1016/s0272-0590(83)80020-7 Publication
Researcher Affiliations
MeSH Terms
- Age Factors
- Animals
- Gentamicins / metabolism
- Gentamicins / toxicity
- Horses
- Injections, Intramuscular
- Injections, Intravenous
- Kidney / drug effects
- Kinetics
- Metabolic Clearance Rate
- Species Specificity
Citations
This article has been cited 5 times.- Aleman MR, True A, Scalco R, Crowe CM, Costa LRR, Chigerwe M. Gentamicin-induced sensorineural auditory loss in healthy adult horses. J Vet Intern Med 2021 Sep;35(5):2486-2494.
- Patil AN, Arora T, Desai A, Tripathi CD. Comparison of the species-sensitive effects of different dosages of calcium and verapamil on gentamicin-induced nephrotoxicity in rats and rabbits. Toxicol Int 2014 Sep-Dec;21(3):225-31.
- Jernigan AD, Hatch RC, Brown J, Crowell WA. Pharmacokinetic and pathological evaluation of gentamicin in cats given a small intravenous dose repeatedly for five days. Can J Vet Res 1988 Apr;52(2):177-80.
- Zhang P, Li Y, Xu P, Zou P, Sheng S, Xiao R, Xu P, Chen Y, Du Y, Ma L, Wang Y. Identification and Exploration of Pyroptosis-Related Genes in Macrophage Cells Reveal Necrotizing Enterocolitis Heterogeneity Through Single-Cell and Bulk-Sequencing. Int J Mol Sci 2025 Apr 24;26(9).
- Huguet AS, Gourbeyre O, Bernand A, Philibert C, Bousquet-Melou A, Lallemand EA, Ferran AA. Comparative bactericidal activity of four macrolides alone and combined with rifampicin or doxycycline against Rhodococcus equi at concentrations achievable in foals. Front Pharmacol 2024;15:1458496.
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