VetCAST method for determination of the pharmacokineticpharmacodynamic cut-off values of a long-acting formulation of florfenicol to support clinical breakpoints for florfenicol Antimicrobial Susceptibility Testing in cattle

Toutain, P-L and Sidhu, P K and Lees, P and Rassouli, A and Pelligand, L (2019) VetCAST method for determination of the pharmacokineticpharmacodynamic cut-off values of a long-acting formulation of florfenicol to support clinical breakpoints for florfenicol Antimicrobial Susceptibility Testing in cattle. Frontiers in Microbiology, 10 (1310).

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Abstract

The PK/PD cut-off (PK/PDCO ) value of florfenicol for calf pathogens was determined for long acting formulations (MSD Nuflor® and a bioequivalent generic product). PK/PDCO is one of the three MICs considered by VetCAST, a sub-committee of the European Committee on Susceptibility Testing, to establish a Clinical Breakpoint for interpreting Antimicrobial Susceptibility Testing. A population model was built by pooling three pharmacokinetic data sets, obtained from 50 richly sampled calves, receiving one of two formulations (the pioneer product and a generic formulation). A virtual population of 5000 florfenicol disposition curves was generated by Monte Carlo Simulations over the 96 h of the assumed duration of action of the formulations. From this population, the maximum predicted MIC, for which 90% of calves can achieve some a priori selected critical value for two PK/PD indices, AUC/MIC and T>MIC, was established. Numerical values were established for two bacterial species of the bovine respiratory disease complex, Pasteurella multocida and Mannheimia haemolytica. It was concluded that the PK/PDCO of florfenicol for both AUC/MIC and T>MIC was 1 mg/L.

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