A population pharmacokinetic model of benzylpenicillin (BP) disposition was developed to compute PK/PD cutoff values for different formulations that are commonly used in equine medicine around the world.

The study analyzed data collected from 40 horses that provided 63 rich profiles of BP corresponding to a total of 1022 individual BP plasma concentrations. The main result of this meta-analysis is that a PK/PD cutoff value of 0.25 mg/L can be guaranteed in 90% of horses for the usual dosage of 12.4 mg/kg per day with the three formulations of procaine BP that have been documented over a sufficient period of time to qualify the full plasma concentration profile (the France, Sweden, and Japan datasets). In contrast, the PK/PD cutoff value is only around 0.0625 mg/L in the case of penethamate and the combination of procaine and benzathine BP, which may still be acceptable for the treatment of more sensitive pathogens such as Streptococcus spp. For IV bolus administration, the routine regimen of 12.36 mg/kg four times at 6-h intervals was also able to achieve a PK/PD cutoff of 0.25 mg/L for all horses.

In conclusion, the PK/PD cutoff of 0.25 mg/L is one dilution lower than the clinical breakpoint released by the Clinical & Laboratory Standards Institute (CLSI; 0.5 mg/ L). From the simulations in this study, the CLSI clinical breakpoint can be achieved with IM procaine BP twice a day at 22,000 IU i.e. 12.4 mg/kg.

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