Rational determination of cefazolin dosage regimen in horses based on pharmacokinetics/pharmacodynamics principles and Monte Carlo simulations - Archive ouverte HAL Access content directly
Journal Articles Journal of Veterinary Pharmacology and Therapeutics Year : 2022

Rational determination of cefazolin dosage regimen in horses based on pharmacokinetics/pharmacodynamics principles and Monte Carlo simulations

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Abstract

A pharmacokinetics/pharmacodynamics (PK/PD) approach was used to determine the best empirical dosage regimen of cefazolin (CEZ) after intramuscular (IM) administration of CEZ in horses. Seven horses received a single IM or intravenous (IV) administration of CEZ of 5 mg/kg bodyweight (BW) according to a crossover design. CEZ plasma concentrations were measured using LC-MS/MS. The plasma concentrations in these seven horses and those of six other horses obtained in a previous study with an IV CEZ dose of 10 mg/kg were modelled simultaneously using NonLinear Mixed-Effect modelling followed by Monte Carlo simulations to establish a rational dosage regimen. A 90% Probability of Target Attainment (PTA) for a PK/PD target of a free plasma concentration exceeding MIC90 (fT > (MIC)) for 40% of the dosing interval was set for selecting an effective dosing regimen. The typical half-life of absorption and bioavailability after IM administration were 1.25 h and 96.8%, respectively. A CEZ dosage regimen of 5 mg/kg BW q12h IM administration achieved therapeutic concentrations to control both Streptococcus zooepidemicus and Staphylococcus aureus. For the same dose, the fT > (MIC) after IM administration was significantly longer than after IV administration, and the IM route should be favoured by clinicians for its efficiency and convenience.
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Dates and versions

hal-03881959 , version 1 (02-12-2022)

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Taisuke Kuroda, Yohei Minamijima, Hiroshi Mita, Norihisa Tamura, Kentaro Fukuda, et al.. Rational determination of cefazolin dosage regimen in horses based on pharmacokinetics/pharmacodynamics principles and Monte Carlo simulations. Journal of Veterinary Pharmacology and Therapeutics, 2022, ⟨10.1111/jvp.13099⟩. ⟨hal-03881959⟩
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