A population pharmacokinetic study of ampicillin therapy in hospitalized foals

Background Pharmacokinetic studies on ampicillin in foals are limited, underscoring a relevant gap in knowledge, particularly regarding the treatment of critically ill neonatal foals. Hypothesis/Objectives To evaluate the adequacy of the ampicillin dosing regimen in hospitalized foals and, if necessary, suggest alternative dosing strategies to achieve effective ampicillin concentrations. Animals Data were collected from 12 hospitalized foals. Methods Foals were treated with 20 mg/kg ampicillin intravenously every 6 h. Plasma samples were obtained within the first 48 h, and the minimum inhibitory concentration (MIC) was determined for pathogen-positive patients. Ampicillin concentrations were quantified using liquid chromatography–tandem mass spectrometry. A population pharmacokinetic model was developed using a nonlinear mixed-effects approach (stochastic approximation expectation–maximization or SAEM algorithm), and a pharmacodynamic evaluation of different dose regimens was conducted using Monte Carlo simulations. Results A 2-compartment model with first-order elimination was selected. Age significantly influenced peripheral compartment volume and clearance. The model demonstrated excellent internal validation, with 97% of observed values within prediction intervals and robust stability, as confirmed by bootstrap and visual predictive checks. Pharmacodynamic simulations indicated that a dosage regimen of 20 mg/kg every 6 h achieved optimal PTA (≥90%) for MICs of 0.06-0.25 mg/L with a 50% fT > MIC target. For higher MICs or a 100% fT > MIC target, more frequent dosing (q4h) and higher doses (30-40 mg/kg) were necessary. Conclusions and clinical importance The results from the simulations highlight the clinical importance of adjusting dosing regimens based on foal characteristics and MIC to ensure effective treatment, especially in critically ill foals.