A Population Pharmacokinetic Model of Gentamicin in Hospitalized Neonatal Foals

Information on safe and effective gentamicin dosing in foals is limited. This study aimed to provide guidance regarding optimal dosing regimens by means of a population pharmacokinetic (popPK) model. Gentamicin plasma concentration of 290 samples from 72 hospitalized foals (≤ 14 days old), treated with intravenous (IV) gentamicin, was measured using a validated LC-MS/MS method. A 2-compartment popPK model was developed with age as a significant covariate on clearance. The final popPK model was used to simulate the commonly used clinical dosing regimens. Mean simulated fAUC_0-24H (10th-90th percentile) in respectively 1-day-old and 14-day-old foals following IV administration of 6.6 mg/kg q24h was 66.3 mg/L*h (44.7-91.2) and 41.9 mg/L*h (26.0-61.0) and following 12 mg/kg q36h 120.5 mg/L*h (81.3-165.8) and 76.2 mg/L*h (47.3-110.9). Trough concentrations were < 2 mg/L for both dosing regimens, irrespective of age. Based on a pharmacodynamic target of fAUC_0-24H/MIC > 80, the 12 mg/kg q36h regimen has a higher probability of target attainment (PTA) than 6.6 mg/kg q24h. A simulated hypothetical dose of 15 mg/kg q36h demonstrated promising PTA with mean trough values ≤ 2 mg/L. Despite substantial interindividual variability, the model provides a rational basis for selecting a dosing regimen in hospitalized neonatal foals.