title: 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 (AUCinf) increased from 25.7 ± 2.9 to 39.0 ± 8.0 mg h/l. Total body clearance (ClB) 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 (Vss) 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 ClBand Vssmet stringent validation criteria. Model for ClBwas used to calculate an optimal dose for a given age group that provides uniform AUCinf. 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.
authors.affiliation: a Department of Biochemistry, Pharmacology and Toxicology, Faculty of Veterinary Medicine , Wrocław University of Environmental and Life Sciences , Wrocław , Poland.
authors.forename: B
authors.initials: B
authors.lastname: Poźniak
authors.affiliation: a Department of Biochemistry, Pharmacology and Toxicology, Faculty of Veterinary Medicine , Wrocław University of Environmental and Life Sciences , Wrocław , Poland.
authors.forename: P
authors.initials: P
authors.lastname: Pawłowski
authors.affiliation: b Department of Internal Diseases with Clinic for Horses, Dogs and Cats, Faculty of Veterinary Medicine , Wrocław University of Environmental and Life Sciences , Wrocław , Poland.
authors.forename: U
authors.initials: U
authors.lastname: Pasławska
authors.affiliation: c Polpharma Biologics , Gdańsk , Poland.
authors.forename: T
authors.initials: T
authors.lastname: Grabowski
authors.affiliation: a Department of Biochemistry, Pharmacology and Toxicology, Faculty of Veterinary Medicine , Wrocław University of Environmental and Life Sciences , Wrocław , Poland.
authors.forename: A
authors.initials: A
authors.lastname: Suszko
authors.affiliation: a Department of Biochemistry, Pharmacology and Toxicology, Faculty of Veterinary Medicine , Wrocław University of Environmental and Life Sciences , Wrocław , Poland.
authors.forename: M
authors.initials: M
authors.lastname: Lis
authors.affiliation: a Department of Biochemistry, Pharmacology and Toxicology, Faculty of Veterinary Medicine , Wrocław University of Environmental and Life Sciences , Wrocław , Poland.
authors.forename: M
authors.initials: M
authors.lastname: Świtała
mesh_terms: D061605:Administration, Intravenous / Q000662:veterinary; D000367:Age Factors; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D001835:Body Weight; D002645:Chickens / Q000254:growth & development / Q000378:metabolism*; D004452:Echocardiography / Q000662:veterinary; D006439:Hemodynamics; D008297:Male; D008954:Models, Biological; D011897:Random Allocation; D013839:Thiamphenicol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; C035534:florfenicol; D013839:Thiamphenicol
keywords: Allometry; broilers; florfenicol; growth; haemodynamics; pharmacokinetics