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

Kuroda, Taisuke; Minamijima, Yohei; Mita, Hiroshi; Tamura, Norihisa; Fukuda, Kentaro; Kuwano, Atsutoshi; Toutain, Pierre‐Louis; Sato, Fumio

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.

Citation

Kuroda, T., Minamijima, Y., Mita, H., Tamura, N., Fukuda, K., Kuwano, A., Toutain, P., & Sato, F. (2022). Rational determination of cefazolin dosage regimen in horses based on pharmacokinetics/pharmacodynamics principles and Monte Carlo simulations. Journal of Veterinary Pharmacology and Therapeutics, https://doi.org/10.1111/jvp.13099

• Journal Article Type: Article
• Acceptance Date: Oct 3, 2022
• Online Publication Date: Oct 17, 2022
• Publication Date: Oct 17, 2022
• Deposit Date: Oct 26, 2022
• Publicly Available Date: Oct 31, 2022
• Journal: Journal of Veterinary Pharmacology and Therapeutics
• Print ISSN: 0140-7783
• Electronic ISSN: 1365-2885
• Publisher: American Academy of Veterinary Pharmacology and Therapeutics
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1111/jvp.13099
• Keywords: General Veterinary; Pharmacology
• Additional Information: Received: 2022-05-26; Accepted: 2022-10-03; Published: 2022-10-17