The influence of rapid growth in broilers on florfenicol pharmacokinetics – allometric modelling of the pharmacokinetic and haemodynamic parameters

ABSTRACT

1. The aim of this study was to determine if the pharmacokinetics (PK) of florfenicol (FF) undergo age-dependent changes in broilers. Since drug elimination depends on cardiovascular functions, a haemodynamic study was performed in parallel.

2. Broilers of 0.68, 1.27, 2.45 and 5.13 kg were administered FF in a single intravenous dose of 30 mg/kg body weight. Plasma drug concentrations were determined using high-performance liquid chromatography and PK parameters were calculated using a non-compartmental model. Echocardiography was used to measure haemodynamic functions.

3. During growth, the area under the drug concentration-time curve (AUC_inf) increased from 25.7 ± 2.9 to 39.0 ± 8.0 mg h/l. Total body clearance (Cl_B) gradually decreased from 1.19 ± 0.14 to 0.80 ± 0.15 l/h/kg. Elimination half-life increased from 0.73 ± 0.08 to 1.07 ± 0.07 h, whereas volume of distribution (V_ss) remained unchanged. Haemodynamic measurements revealed an increase in cardiac output, from 495 ± 65 to 1303 ± 306 ml/min, in the respective body weight groups.

4. Allometric models for PK and haemodynamic parameters were developed and validated. All models proved to be statistically significant; however, only models for Cl_B and V_ss met stringent validation criteria. Model for Cl_B was used to calculate an optimal dose for a given age group that provides uniform AUC_inf.

5. Age-dependent change in FF kinetics may cause variability in therapeutic response under clinical conditions. A novel approach to the dosing protocol was proposed as a means of optimising therapeutic efficacy.

KEYWORDS:

• Allometry
• broilers
• florfenicol
• growth
• haemodynamics
• pharmacokinetics

Acknowledgements

The authors would like to thank Mr Stanisław Sobczuk and Mrs Halina Stępnik for their excellent technical assistance.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Ministry of Science and Higher Education of the Republic of Poland – Fundamental Research Fund for the Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences: [Grant Number: WdW/312/99/2010].