Population pharmacokinetic modeling of gentamicin in dogs
DOI:
https://doi.org/10.5433/1679-0359.2026v47n1p289Keywords:
Aminoglycosides, Canine, Nephrotoxicity, Pharmacometrics, Population pharmacokinetics.Abstract
This study used population pharmacokinetic (popPK) modeling to predict therapeutic efficacy and assess nephrotoxicity risk associated with gentamicin administration in dogs. The model was developed in Monolix 2024 R1 (Lixoft SAS, Simulations Plus Company) using plasma concentrationtime data obtained from the literature. Monte Carlo simulations were subsequently performed in Simulx 2024 (Lixoft SAS, Simulations Plus Company) for gentamicin doses of 2, 4, 6, and 8 mg kg-1 to evaluate therapeutic target attainment and exposure associated with nephrotoxicity risk. The model that best described the observed data was a two-compartment model with linear elimination. Predicted therapeutic efficacy was assessed using the Probability of Target Attainment (PTA) based on the PK/PD target fCmax/MIC ≥ 10 across a range of minimum inhibitory concentrations (MICs). Nephrotoxicity risk was evaluated according to the duration for which plasma gentamicin concentrations remained above the primary nephrotoxicity-risk threshold of 2 μg mL-1. The 8 mg kg-1 regimen achieved PTA values ≥ 90% for pathogens with MIC ≤ 2.0 μg mL-1 and represented the highest-performing simulated regimen among those evaluated. For this regimen, the mean time above the 2 μg mL-1 nephrotoxicity-risk threshold ranged from 4 to 8 hours. These findings support the use of gentamicin against pathogens with MICs ≤ 2 μg mL-1 when administered using extended dosing intervals. However, dose and interval adjustments may be required in critically ill patients. Overall, the popPK approach provides a useful framework for precision dosing, supporting improved predicted efficacy and safety across different dosing regimens.
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Copyright (c) 2026 Kevellyn Silveira Gomes Martins, Larissa Alexandra Félix, Lucas Wamser Fonseca Gonzaga, Karina Krauss Ferraz Vasconcelos, Diego Díaz, João Vitor Fernandes Cotrim de Almeida, Aline Carvalho Pereira, Marcos Ferrante, Nelsa Widerhon
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