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Veterinary surgery : VS2022; 52(1); 87-97; doi: 10.1111/vsu.13896

Potassium penicillin and gentamicin pharmacokinetics in healthy conscious and anesthetized horses.

Abstract: To determine the effects of general anesthesia on the safety and efficacy of co-administered potassium penicillin G (PEN) and gentamicin (GENT) in horses. Methods: Nonrandomized crossover. Methods: Six adult, Thoroughbred horses. Methods: Horses were administered PEN (22 000 IU/kg IV) and GENT (6.6 mg/kg IV). Plasma samples were collected over a 6 h period and synovial fluid was collected at 30 min and 6 h respectively. Drug administration and sample collection protocols were repeated after at least a 48 hour washout period and induction of anesthesia using xylazine/ketamine and maintenance with isoflurane gas. Drug concentrations were determined using ultrapressure liquid chromatography with mass spectrometry. A 2-compartment model was used to determine pharmacokinetics and differences were determined between conscious and anesthetized horses using paired t-tests (significance P < .05). Results: Potassium penicillin g and GENT had higher minimum plasma concentrations (PEN 0.44 vs. 0.11 μg/mL, P = .002; GENT 3.0 vs. 1.9 μg/mL, P = .009), longer half lives (PEN 71 vs. 59 min, P = .018; GENT 149 vs. 109 min, P = .038), and slower clearances (PEN 3.41 vs. 5.1 mL/kg/min, P = .005; GENT 1.18 vs. 1.48 mL/kg/min, P = .028) in anesthetized horses vs. conscious horses. The PEN concentrations remained above the breakpoint minimum inhibitory concentration (MIC, 0.5 μg/mL) for 332 min in anesthetized vs. 199 min in conscious horses. The GENT concentrations reached 10 times higher than the breakpoint MIC (2 μg/mL) in all horses and were maintained for 58 vs. 59 min in anesthetized and conscious states, respectively. Synovial fluid concentrations were higher in conscious horses vs. anesthetized horses at 30 min for PEN (7.0 vs. 0.93 μg/mL, P < .001) and 30 (5.3 μg/mL vs. 0.79 μg/mL, P < .001) and 360 min (3.4 vs. 1.82 μg/mL, P < .003) for GENT. Conclusions: General anesthesia resulted in lower intrasynovial concentrations and delayed clearance of PEN/GENT in horses. Conclusions: Redosing healthy anesthetized horses with PEN prior to 4-5 h is not necessary. When administered to anesthetized horses, intravenous PEN/GENT may not reach adequate intrasynovial concentrations to treat or prevent common pathogens. The doses or dosing intervals of antimicrobials administered to horses undergoing anesthesia may need to be adjusted to ensure maintenance of safe and effective plasma concentrations.
© 2022 American College of Veterinary Surgeons.
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Publication Date: 2022-10-26 PubMed ID: 36286077DOI: 10.1111/vsu.13896Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article explores the effects of general anesthesia on how potassium penicillin G and gentamicin, two commonly administered drugs, are absorbed and processed in horses.

Methods

  • The study conducted was nonrandomized crossover in design, involving six adult, Thoroughbred horses.
  • Both potassium penicillin G and gentamicin were administered to these horses, and plasma samples were taken over a six-hour period. Synovial fluid was also collected at two points: 30 minutes and six hours after administration.
  • This drug administration and sample collection process was repeated after a minimum of 48 hours (a washout period). In this next round, anesthesia was induced using a mixture of xylazine, ketamine, and then maintained with isoflurane gas.
  • Utrapressure liquid chromatography along with mass spectrometry were used to determine the drug concentrations. A 2-compartment model allowed the team to figure out the pharmacokinetics.
  • Comparisons were then made between the results from conscious and anesthetized horses, using paired t-tests to identify significant differences.

Results

  • The researchers found that both potassium penicillin G and gentamicin demonstrated higher minimum plasma concentrations, longer half-lives, and slower clearances in anesthetized horses when compared to conscious horses.
  • The synovial fluid concentrations were also found to be significantly higher in conscious horses, as compared to anesthetized horses.

Conclusions

  • The study concluded that general anesthesia results in lower intrasynovial concentrations and delayed clearance of both drugs in horses.
  • The findings suggest that there is no need to redose healthy, anesthetized horses with PEN within 4-5 hours. However, when administered to anesthetized horses, intravenous potassium penicillin G and gentamicin may not reach adequate intrasynovial concentrations to prevent or treat common pathogens.
  • The research implies that the doses or dosing intervals of antimicrobials administered to horses under anesthesia might need to be adjusted to maintain safe and effective plasma concentrations.

Cite This Article

APA
Wilson KE, Bogers SH, Council-Troche RM, Davis JL. (2022). Potassium penicillin and gentamicin pharmacokinetics in healthy conscious and anesthetized horses. Vet Surg, 52(1), 87-97. https://doi.org/10.1111/vsu.13896

Publication

Veterinary surgery : VS
ISSN: 1532-950X
NlmUniqueID: 8113214
Country: United States
Language: English
Volume: 52
Issue: 1
Pages: 87-97

Researcher Affiliations

Wilson, Katherine E
  • Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, USA.
Bogers, Sophie H
  • Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, USA.
Council-Troche, R McAlister
  • Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, USA.
Davis, Jennifer L
  • Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, USA.

MeSH Terms

  • Horses
  • Animals
  • Penicillins
  • Gentamicins / pharmacology
  • Penicillin G / pharmacokinetics
  • Xylazine / pharmacology
  • Isoflurane

Grant Funding

  • Equine Research Competition, Virginia-Maryland College of Veterinary Medicine

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Citations

This article has been cited 2 times.
  1. Ferran AA, Roques BB, Chapuis L, Kuroda T, Lacroix MZ, Toutain PL, Bousquet-Melou A, Lallemand EA. Predicted efficacy and tolerance of different dosage regimens of benzylpenicillin in horses based on a pharmacokinetic study with three IM formulations and one IV formulation. Front Vet Sci 2024;11:1409266.
    doi: 10.3389/fvets.2024.1409266pubmed: 38881781google scholar: lookup
  2. Lallemand EA, Bousquet-Mélou A, Chapuis L, Davis J, Ferran AA, Kukanich B, Kuroda T, Lacroix MZ, Minamijima Y, Olsén L, Pelligand L, Portugal FR, Roques BB, Santschi EM, Wilson KE, Toutain PL. Pharmacokinetic-pharmacodynamic cutoff values for benzylpenicillin in horses to support the establishment of clinical breakpoints for benzylpenicillin antimicrobial susceptibility testing in horses. Front Microbiol 2023;14:1282949.
    doi: 10.3389/fmicb.2023.1282949pubmed: 37954237google scholar: lookup
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