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Home / Equine Research Bank / Equine Vet J / Rational dosage regimens for cephalothin and cefazolin using...
Equine veterinary journal2021; 53(6); 1239-1249; doi: 10.1111/evj.13406

Rational dosage regimens for cephalothin and cefazolin using pharmacokinetics and pharmacodynamics analysis in healthy horses.

Abstract: First-generation cephalosporins have good activity against gram-positive bacteria and are extensively used in horses. There are few reports of pharmacokinetics and pharmacodynamics (PK/PD) analysis of cephalosporins in horses. Objective: To optimise the dosages of the two first-generation cephalosporins cephalothin (CET) and cefazolin (CEZ) in horses using PK/PD concepts. Methods: Experimental study with single administration. Methods: Drug plasma concentrations following a single intravenous (i.v.) administration of 22 mg/kg bodyweight (bwt) CET in 12 horses and of 10 mg/kg bwt CEZ in six horses were measured using LC-MS/MS. Data were modelled using a nonlinear mixed effect modelling followed by Monte Carlo simulations. Minimum inhibitory concentrations (MICs) against Streptococcus zooepidemicus and Staphylococcus aureus isolated from horses were determined by the microbroth dilution method. Results: The percentages of CET and CEZ binding to serum proteins were 19.9% ± 8.4% and 15.2% ± 8.5% respectively. For both CET and CEZ, the MIC90 against S. zooepidemicus was 0.12 mg/L and against S. aureus was 0.5 mg/L. For CET, to achieve a probability of target attainment (PTA) of 90% for a PK/PD target of a free serum plasma concentration exceeding the MIC90 for 40% of the dosing interval, an empirical CET dosage regimen of 22 mg/kg bwt q8h and 22 mg/kg bwt q4h i.v. administration were required for S. zooepidemicus and S. aureus respectively. For CEZ, the corresponding dosage regimens were 10 mg/kg bwt q12h and 10 mg/kg bwt q8h. Conclusions: Small sample size only in healthy horses. Conclusions: For CET, more frequent administration than that currently recommended (22 mg/kg bwt q6-12h) is required to empirically control S. aureus infection in horses. For CEZ, less frequent administration compared to the dosage regimen currently proposed (10-22 mg/kg bwt q6h) could control S. zooepidemicus and S. aureus infections in horses.
2020 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
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Publication Date: 2021-01-21 PubMed ID: 33341979PubMed Central: PMC8518962DOI: 10.1111/evj.13406Google Scholar: Lookup
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Summary

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The study aims to optimize the dosages of two first-generation cephalosporins, namely cephalothin (CET) and cefazolin (CEZ), in horses through pharmacokinetics and pharmacodynamics (PK/PD) analysis.

Methods

  • The research was an experimental study involving single administration of these drugs. 22 mg/kg bodyweight of CET was administered intravenously in 12 horses, and 10 mg/kg bodyweight of CEZ was administered in six horses.
  • The plasma concentrations of these drugs post-administration were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
  • The data collected was modelled employing the nonlinear mixed effect modelling technique, after which Monte Carlo simulations were performed.
  • The study also involved determining the Minimum Inhibitory Concentrations (MICs) against Streptococcus zooepidemicus and Staphylococcus aureus, two bacterial strains frequently found in horses. MICs were calculated using the microbroth dilution method.

Results

  • Results showed that the percentages of CET and CEZ binding to serum proteins were 19.9% ± 8.4% and 15.2% ± 8.5%, respectively.
  • For both drugs, the MIC against Streptococcus zooepidemicus was 0.12 mg/L, while it was 0.5 mg/L against Staphylococcus aureus.
  • To achieve a probability of target attainment (PTA) of 90%, it was found that CET dosage of 22 mg/kg bodyweight should be administered every 8 hours for S. zooepidemicus while the same dosage should be administered every 4 hours for S. aureus.
  • CEZ dosage of 10 mg/kg bodyweight is required every 12 hours for S. zooepidemicus, and every 8 hours for S. aureus to achieve a 90% PTA.

Conclusions

  • The conclusions were drawn based on a small sample size of only healthy horses.
  • A higher frequency of CET administration than currently recommended is necessary to control S. aureus infection in horses.
  • In comparison, a lower frequency of CEZ administration than currently recommended could effectively control both S. zooepidemicus and S. aureus infections in horses.

Cite This Article

APA
Kuroda T, Minamijima Y, Niwa H, Tamura N, Mita H, Fukuda K, Kaimachi M, Suzuki Y, Enoki Y, Taguchi K, Matsumoto K, Toutain PL, Bousquet-Melou A, Kasashima Y. (2021). Rational dosage regimens for cephalothin and cefazolin using pharmacokinetics and pharmacodynamics analysis in healthy horses. Equine Vet J, 53(6), 1239-1249. https://doi.org/10.1111/evj.13406

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 53
Issue: 6
Pages: 1239-1249

Researcher Affiliations

Kuroda, Taisuke
  • Clinical Veterinary Medicine Division Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.
Minamijima, Yohei
  • Drug Analysis Department, Laboratory of Racing Chemistry, Utsunomiya, Japan.
Niwa, Hidekazu
  • Microbiology Division Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.
Tamura, Norihisa
  • Clinical Veterinary Medicine Division Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.
Mita, Hiroshi
  • Clinical Veterinary Medicine Division Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.
Fukuda, Kentaro
  • Clinical Veterinary Medicine Division Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.
Kaimachi, Masahiro
  • Division of Pharmacodynamics, Keio University Faculty of Pharmacy Tokyo, Japan.
Suzuki, Yuto
  • Division of Pharmacodynamics, Keio University Faculty of Pharmacy Tokyo, Japan.
Enoki, Yuki
  • Division of Pharmacodynamics, Keio University Faculty of Pharmacy Tokyo, Japan.
Taguchi, Kazuaki
  • Division of Pharmacodynamics, Keio University Faculty of Pharmacy Tokyo, Japan.
Matsumoto, Kazuaki
  • Division of Pharmacodynamics, Keio University Faculty of Pharmacy Tokyo, Japan.
Toutain, Pierre-Louis
  • Comparative Biomedical Sciences, The Royal Veterinary College, London, UK.
Bousquet-Melou, Alain
  • INTHERES, Université de Toulouse, INRA, ENVT, Toulouse, France.
Kasashima, Yoshinori
  • Clinical Veterinary Medicine Division Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.

MeSH Terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Cefazolin / pharmacology
  • Cephalothin
  • Chromatography, Liquid / veterinary
  • Horses
  • Microbial Sensitivity Tests / veterinary
  • Staphylococcus aureus
  • Tandem Mass Spectrometry / veterinary

Conflict of Interest Statement

No competing interests have been declared.

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