Pharmacokinetics, pharmacodynamic efficacy prediction indices, and Monte Carlo simulations of enrofloxacin for the treatment of colibacillosis in broiler chickens.

Abstract

BACKGROUND: Enrofloxacin is one of the most used antibiotics for the treatment of respiratory and gastrointestinal tract diseases in poultry farming worldwide. Pharmacokinetics/pharmacodynamics (PK/PD) modeling is a strategy that allows dose optimization for antibiotic therapy by considering relevant bacteria's microbiological aspects. AIM: This study aimed to establish a pharmacokinetic model of enrofloxacin in broilers using a nonlinear mixed-effects Model and predict the effectiveness of various oral dosing regimens across a distribution ofminimum inhibitory concentrations (MIC) for two PK/PD targets (AUC/MIC ≥ 125 andAUC/MIC = 28.32). METHODS: A PK model was constructed using the Monolix 2024R1 software based on previously published data, which involved 12 clinically healthy male Cobb broilers (38-40 days old, 2.27 ± 0.95 kg). This model served as the basis for Monte Carlo simulations (single oral dose of 10, 20, 30, and 50 mg/kg) and the probability of target attainment (PTA) analysis. The PTA for each protocol was evaluated according to the distribution of MICs considering two PK/PD targets to ensure a comprehensive assessment of treatment efficacy. RESULTS: The best-fit PK model that evaluated the PK of enrofloxacin following intravenous and oral administration was a two-compartment model with first-order absorption and linear elimination. Given the calculated epidemiological cutoff value of 0.125 μg/ml, a dose of 10 mg/kg is adequate for theAUC/MIC ≥ 28.32 target, but insufficient for theAUC/MIC ≥ 125 target, which requires a higher dose of 20 mg/kg. CONCLUSION: The PK/PD approach applied in Cobb broiler chickens demonstrates the potential for dose optimization based on MIC distribution, supporting Antimicrobial Stewardship efforts. However, further complementary studies are required to evaluate the predictive capabilities of these indices and to establish the optimal PK/PD targets forefficacy.