An open source interactive physiologically based pharmacokinetic (iPBPK) model of tylosin in broiler chickens and laying hens.

Abstract

Tylosin, a broad-spectrum macrolide antibiotic, is used to treat chronic respiratory infectious diseases in both urban and commercial broiler chickens and laying hens in an extra-label manner. To ensure food safety and facilitate extra-label withdrawal interval (WDI) estimations, a physiologically based pharmacokinetic (PBPK) model for tylosin in broiler chickens and laying hens was developed. The model structure encompassed plasma, crop, gizzard, small intestine, colon, muscle, liver, kidney, fat, rest of body, and an integrated reproductive system consisting of the ovary and oviduct (for hens). This model adequately predicted the pharmacokinetics of tylosin in plasma, tissues, egg yolk and white under different scenarios in both broilers and layers with determination coefficients of 0.87 and 0.78, respectively. The model was converted to a user-friendly web-based interface. The estimated WDIs were 2.0, 3.0, 4.0, 2.0, and 2.0 days for eggs, kidney, liver, muscle, and fat, respectively, based on FDA tolerance after daily oral administration at 110 mg/kg tylosin via medicated water for five consecutive days in laying hens. This model provides a useful and flexible tool for food safety assessment of tylosin in chickens and lays the groundwork for extrapolating to other drugs in other poultry species.