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Pharmacokinetics of dexamethasone in broiler chickens

Anneleen Watteyn UGent, Heidi Wyns UGent, Elke Plessers UGent, Siegrid De Baere UGent, Patrick De Backer UGent and Siska Croubels UGent (2012) JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS.
abstract
Dexamethasone (DEX) is a synthetic derivate of cortisol and is one of the most potent glucocorticoids in man and animal. It is well known as an anti-inflammatory drug in many species. In poultry, however, data on the use of DEX are scarce. DEX would be a possible candidate-drug to influence mediators like cytokines and acute phase proteins in a lipopolysaccharide (LPS) inflammation model. First of all, it is important to determine the pharmacokinetics to investigate the immunomodulating properties of this drug. Data on disposition of DEX in broilers are unknown. The aim of this study was to investigate several pharmacokinetic parameters (area under the curve, AUC; absorption and elimination rate constant, kabs and kel; half-life of absorption and elimination, t1/2abs and t1/2el; volume of distribution, Vd; clearance, Cl; maximum plasma concentration at 0 h; maximum plasma concentration, Cmax; time to Cmax, Tmax and absolute bioavailability, F) of DEX in broiler chickens. The DEX experiment was performed as a two-way cross-over design, each group containing three 4-week-old broiler chickens and with a wash-out period of 96 hours. The animals received a bolus of 0.3 mg/kg body weight DEX intravenously (IV) in the wing vein or intramuscularly (IM) in the pectoral muscle. Blood (1 ml) was sampled by venipuncture from the leg vein before (time 0) and post-administration (0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours). Plasma was stored at ≤ -15°C until analysis. Quantitation of DEX in plasma was carried out using in-house developed and validated LC-MS/MS methods. The pharmacokinetic parameters were analyzed using WinNonlin, version 6.2.0 (Pharsight). The pharmacokinetics of DEX were analyzed according to a one-compartmental model (see Table 1). After IM administration, the maximum plasma concentration was reached fast at 0.37 h. In contrast to many other species, t1/2el of the corticosteroid was very short. The clearance in chickens was 1.26 L/h.kg, which is higher than for mammals. The Vd amounted to 1 L/kg and is equal to values found in other species. In chickens, a bioavailability of 100% after IM administration of DEX could be calculated, indicating a complete absorption of the drug. The pharmacokinetics hereby presented, will be very useful in an in-house developed LPS-inflammation model in broiler chickens.
Please use this url to cite or link to this publication:
author
organization
year
type
conference
publication status
in press
subject
keyword
Chicken, Pharmacokinetics, Bioavailability, Dexamethasone
in
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
J. Vet. Pharmacol. Ther.
conference name
12th International congress of the European Association for Veterinary Pharmacology and Toxicology (EAVPT)
conference location
Noordwijkerhout, The Netherlands
conference start
2012-07-08
conference end
2012-07-12
JCR category
VETERINARY SCIENCES
JCR impact factor
1.349 (2012)
JCR rank
43/142 (2012)
JCR quartile
2 (2012)
ISSN
0140-7783
language
English
UGent publication?
yes
classification
C3
additional info
uploaded document is poster version
copyright statement
I have transferred the copyright for this publication to the publisher
id
2968748
handle
http://hdl.handle.net/1854/LU-2968748
date created
2012-08-07 09:57:15
date last changed
2012-08-09 15:05:06
@inproceedings{2968748,
  abstract     = {Dexamethasone (DEX) is a synthetic derivate of cortisol and is one of the most potent glucocorticoids in man and animal. It is well known as an anti-inflammatory drug in many species. In poultry, however, data on the use of DEX are scarce. 
DEX would be a possible candidate-drug to influence mediators like cytokines and acute phase proteins in a lipopolysaccharide (LPS) inflammation model. First of all, it is important to determine the pharmacokinetics to investigate the immunomodulating properties of this drug. Data on disposition of DEX in broilers are unknown. The aim of this study was to investigate several pharmacokinetic parameters (area under the curve, AUC; absorption and elimination rate constant, kabs and kel; half-life of absorption and elimination, t1/2abs and t1/2el; volume of distribution, Vd; clearance, Cl; maximum plasma concentration at 0 h; maximum plasma concentration, Cmax; time to Cmax, Tmax and absolute bioavailability, F) of DEX in broiler chickens. 
The DEX experiment was performed as a two-way cross-over design, each group containing three 4-week-old broiler chickens and with a wash-out period of 96 hours. The animals received a bolus of 0.3 mg/kg body weight DEX intravenously (IV) in the wing vein or intramuscularly (IM) in the pectoral muscle. Blood (1 ml) was sampled by venipuncture from the leg vein before (time 0) and post-administration (0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours). Plasma was stored at \ensuremath{\leq} -15{\textdegree}C until analysis. Quantitation of DEX in plasma was carried out using in-house developed and validated LC-MS/MS methods. The pharmacokinetic parameters were analyzed using WinNonlin, version 6.2.0 (Pharsight).
The pharmacokinetics of DEX were analyzed according to a one-compartmental model (see Table 1). After IM administration, the maximum plasma concentration was reached fast at 0.37 h. In contrast to many other species, t1/2el of the corticosteroid was very short. The clearance in chickens was 1.26 L/h.kg, which is higher than for mammals. The Vd amounted to 1 L/kg and is equal to values found in other species. In chickens, a bioavailability of 100\% after IM administration of DEX could be calculated, indicating a complete absorption of the drug.
The pharmacokinetics hereby presented, will be very useful in an in-house developed LPS-inflammation model in broiler chickens.},
  author       = {Watteyn, Anneleen and Wyns, Heidi and Plessers, Elke and De Baere, Siegrid and De Backer, Patrick and Croubels, Siska},
  booktitle    = {JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS},
  issn         = {0140-7783},
  keyword      = {Chicken,Pharmacokinetics,Bioavailability,Dexamethasone},
  language     = {eng},
  location     = {Noordwijkerhout, The Netherlands},
  title        = {Pharmacokinetics of dexamethasone in broiler chickens},
  year         = {2012},
}

Chicago
Watteyn, Anneleen, Heidi Wyns, Elke Plessers, Siegrid De Baere, Patrick De Backer, and Siska Croubels. 2012. “Pharmacokinetics of Dexamethasone in Broiler Chickens.” In Journal of Veterinary Pharmacology and Therapeutics.
APA
Watteyn, A., Wyns, H., Plessers, E., De Baere, S., De Backer, P., & Croubels, S. (2012). Pharmacokinetics of dexamethasone in broiler chickens. JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS. Presented at the 12th International congress of the European Association for Veterinary Pharmacology and Toxicology (EAVPT).
Vancouver
1.
Watteyn A, Wyns H, Plessers E, De Baere S, De Backer P, Croubels S. Pharmacokinetics of dexamethasone in broiler chickens. JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS. 2012.
MLA
Watteyn, Anneleen, Heidi Wyns, Elke Plessers, et al. “Pharmacokinetics of Dexamethasone in Broiler Chickens.” Journal of Veterinary Pharmacology and Therapeutics. 2012. Print.