title: Pharmacokinetics of repeated sodium salicylate administration to laying hens: evidence for time dependent increase in drug elimination from plasma and eggs.
abstract: Salicylates were the first non-steroid anti-inflammatory drugs (NSAIDs) to be used in any species and are still widely used in humans and livestock. However, the data on their pharmacokinetics in animals is limited, especially after repeated administration. Evidence exist that in chickens (Gallus gallus) salicylate (SA) may induce its own elimination. The aim of this study was to investigate salicylate pharmacokinetics and egg residues during repeated administration of sodium salicylate (SS) to laying hens. Pharmacokinetics of SA was assessed during 14 d oral administration of SS at daily doses of 50 mg/kg and 200 mg/kg body weight to laying hens. On the 1st, 7th and 14th d a 24 h-long pharmacokinetic study was carried out, whereas eggs were collected daily. Salicylate concentrations in plasma and eggs were determined using high-performance liquid chromatography with ultraviolet detection and pharmacokinetic variables were calculated using a non-compartmental model. Mean residence time (MRT), minimal plasma concentration (Cmin, C16h) and elimination half-life (T1/2el) of SA showed gradual decrease in layers administered with a lower dose. Total body clearance (ClB) increased. Layers administered with the higher dose showed a decrease only in the T1/2el. In the low dose group, SA was found only in the egg white and was low throughout the experiment. Egg whites from the higher dose group showed initially high SA levels which significantly decreased during the experiment. Yolk SA levels were lower and showed longer periods of accumulation and elimination. Repeated administration of SS induces SA elimination, although this effect may differ depending on the dose and production type of a chicken. Decreased plasma drug concentration may have clinical implications during prolonged SS treatment.
authors.affiliation: Department of Biochemistry, Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
authors.forename: Błażej
authors.initials: B
authors.lastname: Poźniak
authors.affiliation: Polpharma Biologics, Gdańsk, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Grabowski
authors.affiliation: Department of Biochemistry, Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Motykiewicz-Pers
authors.affiliation: Department of Epizootiology and Clinic of Birds and Exotic Animals, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
authors.forename: Kamila
authors.initials: K
authors.lastname: Bobrek
authors.affiliation: Department of Food Hygiene and Consumer Health Protection, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
authors.forename: Lech
authors.initials: L
authors.lastname: Rak
authors.affiliation: Department of Epizootiology and Clinic of Birds and Exotic Animals, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bobusia
authors.affiliation: Department of Epizootiology and Clinic of Birds and Exotic Animals, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Gaweł
authors.affiliation: Department of Biochemistry, Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Świtała
mesh_terms: D000818:Animals; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D004529:Egg White; D004530:Egg Yolk / Q000187:drug effects / Q000378:metabolism; D005260:Female; D010058:Oviposition / Q000187:drug effects*; D010063:Ovum / Q000378:metabolism*; D012980:Sodium Salicylate / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics* / Q000494:pharmacology; D013997:Time Factors
chemical_list: D012980:Sodium Salicylate