Pharmacokinetics/pharmacodynamics cut-off determination for fosfomycin using Monte Carlo simulation in healthy horses
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- KURODA Taisuke
- Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Tochigi, Japan
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- MINAMIJIMA Yohei
- Drug Analysis Department, Laboratory of Racing Chemistry, Tochigi, Japan
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- NIWA Hidekazu
- Microbiology Division, Equine Research Institute, Japan Racing Association, Tochigi, Japan
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- MITA Hiroshi
- Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Tochigi, Japan
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- TAMURA Norihisa
- Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Tochigi, Japan
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- FUKUDA Kentaro
- Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Tochigi, Japan
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- TOUTAIN Pierre-Louis
- Comparative Biomedical Sciences, The Royal Veterinary College, London, United Kingdom Intheres, Ecole Nationale Vétérinaire de Toulouse, France
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- OHTA Minoru
- Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Tochigi, Japan
抄録
<p>Fosfomycin (FOM) is an approved veterinary medicinal product for large animals in Japan, but Clinical breakpoint (CBP) for antimicrobial susceptibility test (AST) is not defined for animals. This study aimed at conducting a pharmacokinetics/pharmacodynamics (PK/PD) analysis to determine the PK/PD cutoff for the CBP in horses. Drug concentrations following single intravenous administration (IV) of 20 mg/kg body weight (BW) FOM in nine horses were measured using liquid chromatography/mass spectrometry. The data were modelled using a nonlinear mixed-effects model, followed by Monte Carlo simulations. A 90% probability of target attainment for a PK/PD target of the ratio of Area Under the free plasma concentration-time curve divided by the minimal inhibitory concentration (MIC) >24 hr was set as PK/PD cut-off. The PK/PD cutoff for FOM 20 mg/kg BW q12 hr IV was estimated with the MIC value of ≤16.0 mg/L, and this regimen was considered effective against E. coli (MIC90; 16.0 mg/L) in healthy horses based on the MIC90 values of the wild population. Owing to the relevance of FOM to human health, veterinarians should use q 12 hr FOM 20 mg /kg against E. coli infections with an MIC <16 µg/mL, as suggested by our PK/PD cutoff after AST.</p>
収録刊行物
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- Ｔｈｅ Ｊｏｕｒｎａｌ ｏｆ Ｖｅｔｅｒｉｎａｒｙ Ｍｅｄｉｃａｌ Ｓｃｉｅｎｃｅ
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Ｔｈｅ Ｊｏｕｒｎａｌ ｏｆ Ｖｅｔｅｒｉｎａｒｙ Ｍｅｄｉｃａｌ Ｓｃｉｅｎｃｅ 86 (4), 413-420, 2024
公益社団法人 日本獣医学会