A population pharmacokinetic study of ampicillin therapy in hospitalized foals

Abstract

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.