Enrofloxacin Dose Optimization for the Treatment of Colibacillosis in Broiler Chickens Using a Drinking Behaviour Pharmacokinetic Model
Robin Temmerman, Ludovic Pelligand, Wim Schelstraete, Gunther Antonissen, An Garmyn, Mathias Devreese
Abstract
Enrofloxacin is frequently administered via drinking water for the treatment of colibacillosis in broiler chickens. However, the EMA/CVMP has urged to re-evaluate historically approved doses, especially for antimicrobials administered via drinking water. In response, the objectives of this study were two-fold. First, to evaluate the pharmacokinetics (PK) of enrofloxacin following IV, PO and drinking water administration. Second, to predict the efficacy of a range of doses in the drinking water for the treatment of APEC infections. For the first objective, PK parameters were estimated by fitting a one-compartmental model with a zero-order IV infusion and an oral absorption lag function to the simultaneously modelled IV and PO data. After fixing these parameter values, a drinking behaviour pharmacokinetic (DBPK) model was developed for the description and prediction of drinking water PK profiles by adding three model improvements (different diurnal and nocturnal drinking rates, inter-animal variability in water consumption and taking account of dose non-proportionality). The subsequent simulations and probability of target attainment (PTA) analysis predicted that a dose of 12.5 mg/kg/24 h is efficacious in treating colibacillosis with an MIC up to 0.125 μg/mL (ECOFF), whereas the currently registered dose (10 mg/kg/24 h) reaches a PTA of 66% at ECOFF.