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Pharmacokinetics of dexamethasone in pigs

Heidi Wyns UGent, Evelyne Meyer UGent, Anneleen Watteyn UGent, Elke Plessers UGent, Siegrid De Baere UGent, Patrick De Backer UGent and Siska Croubels UGent (2012) JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS.
abstract
Introduction : Dexamethasone (DEX), a synthetic long-acting corticosteroid is extensively used in veterinary practice as it possesses major anti-inflammatory effects (Ferguson et al., 2009). Gamithromycin (GAMI) is a novel 15-membered semi-synthetic macrolide antibiotic of the azalide subclass recently developed for the treatment and prevention of bovine respiratory disease. Besides the anti-infectious properties, macrolides have frequently been reported to affect various inflammatory processes, such as the production of pro-inflammatory cytokines and mediators (Kanoh and Rubin, 2010). The aim of this study was therefore to determine the pharmacokinetic (PK) parameters of DEX and GAMI in pigs, which can be used in further research to investigate the individual and synergistic immunomodulatory properties of both drugs in a porcine lipopolysaccharide (LPS) inflammation model. Materials and Methods : For DEX, the experiment was performed as a two-way cross-over design. Six 9-week-old male pigs received an injection of 0.3 mg/kg body weight (BW) DEX (Dexa 0.2%®, Kela) intravenously (IV) and intramuscularly (IM). Blood was collected from the jugular vein into EDTA tubes before and post administration (p.a.) at 15, 30, 45 minutes and 1, 2, 4, 6, 8, 12 and 24 h. Plasma was isolated and stored at ≤ -15°C until analysis. For GAMI, twelve 9-week-old male pigs were randomly divided in two groups. The animals received a single injection of 6 mg/kg BW GAMI (Zactran®, Merial), either IV (n = 6) or subcutaneously (SC) (n = 6). Blood was collected from the jugular vein into EDTA tubes before administration; on day 0 at 15, 30 and 45 minutes and 1, 2, 4, 6, 8, 10, 12 and 24 h p.a. and once daily from day 2 to day 14 p.a. (24 h intervals). Plasma was isolated and stored at ≤ -15°C until analysis. Quantitation of DEX and GAMI in the plasma samples was performed using in-house developed and validated LC-MS/MS methods. The pharmacokinetic parameters were analyzed using the software program WinNonlin 6.2.0 (Pharsight). Results and Conclusions : The area under the plasma concentration-time curve (AUC0→∞), absolute bioavailability (F), half-life of absorption and elimination (t1/2abs and t1/2el, respectively), volume of distribution (Vd), clearance (Cl), maximum plasma concentration (Cmax) and time to Cmax (Tmax) were determined for DEX and GAMI. The PK parameters of the innovative macrolide GAMI were compared to those in cattle and foals (Huang et al., 2010; Berghaus et al., 2011). Additionally, the effects of DEX, GAMI and the combination of both drugs on the synthesis and release of TNF-α and IL-6 will be studied in LPS-challenged pigs. Results and conclusions will be presented at the congress. References Ferguson D.C., Dirikolu L., Hoenig M. (2009). Glucocorticoids, Mineralocorticoids, and Adrenolytic drugs. In Veterinary Pharmacology and Therapeutics, 9th Ed. Eds Riviere J.E., Papich M.G. Wiley-Blackwell, Iowa, USA, pp 771-802. Kanoh S. and Rubin B.K. (2010). Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications. Clinical Microbiology Reviews, 23, 590-615. Huang R.A., Letendre L.T., Banav N., Fischer J., Somerville B. (2011). Pharmacokinetics of gamithromycin in cattle with comparison of plasma and lung tissue concentrations and plasma antibacterial activity. Journal of Veterinary Pharmacology and Therapeutics, 33, 227-237. Berghaus L.J., Giguère S., Sturgill T.L., Bade D., Malinski T.J., Huang R. (2012). Plasma pharmacokinetics, pulmonary distribution, and in vitro activity of gamithromycin in foals. Journal of Veterinary Pharmacology and Therapeutics, 35, 59-65.
Please use this url to cite or link to this publication:
author
organization
year
type
conference
publication status
in press
subject
keyword
bioavailability, pigs, pharmacokinetics, 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
copyright statement
I have transferred the copyright for this publication to the publisher
id
2961755
handle
http://hdl.handle.net/1854/LU-2961755
date created
2012-07-12 14:33:02
date last changed
2012-08-09 14:55:57
@inproceedings{2961755,
  abstract     = {Introduction : Dexamethasone (DEX), a synthetic long-acting corticosteroid is extensively used in veterinary practice as it possesses major anti-inflammatory effects (Ferguson et al., 2009). Gamithromycin (GAMI) is a novel 15-membered semi-synthetic macrolide antibiotic of the azalide subclass recently developed for the treatment and prevention of bovine respiratory disease. Besides the anti-infectious properties, macrolides have frequently been reported to affect various inflammatory processes, such as the production of pro-inflammatory cytokines and mediators (Kanoh and Rubin, 2010). The aim of this study was therefore to determine the pharmacokinetic (PK) parameters of DEX and GAMI in pigs, which can be used in further research to investigate the individual and synergistic immunomodulatory properties of both drugs in a porcine lipopolysaccharide (LPS) inflammation model.
Materials and Methods : For DEX, the experiment was performed as a two-way cross-over design. Six 9-week-old male pigs received an injection of 0.3 mg/kg body weight (BW) DEX (Dexa 0.2\%{\textregistered}, Kela) intravenously (IV) and intramuscularly (IM). Blood was collected from the jugular vein into EDTA tubes before and post administration (p.a.) at 15, 30, 45 minutes and 1, 2, 4, 6, 8, 12 and 24 h. Plasma was isolated and stored at \ensuremath{\leq} -15{\textdegree}C until analysis. For GAMI, twelve 9-week-old male pigs were randomly divided in two groups. The animals received a single injection of 6 mg/kg BW GAMI (Zactran{\textregistered}, Merial), either IV (n = 6) or subcutaneously (SC) (n = 6). Blood was collected from the jugular vein into EDTA tubes before administration; on day 0 at 15, 30 and 45 minutes and 1, 2, 4, 6, 8, 10, 12 and 24 h p.a. and once daily from day 2 to day 14 p.a. (24 h intervals). Plasma was isolated and stored at \ensuremath{\leq} -15{\textdegree}C until analysis. Quantitation of DEX and GAMI in the plasma samples was performed using in-house developed and validated LC-MS/MS methods. The pharmacokinetic parameters were analyzed using the software program WinNonlin 6.2.0 (Pharsight).
Results and Conclusions : The area under the plasma concentration-time curve (AUC0{\textrightarrow}\ensuremath{\infty}), absolute bioavailability (F), half-life of absorption and elimination (t1/2abs and t1/2el, respectively), volume of distribution (Vd), clearance (Cl), maximum plasma concentration (Cmax) and time to Cmax (Tmax) were determined for DEX and GAMI. The PK parameters of the innovative macrolide GAMI were compared to those in cattle and foals (Huang et al., 2010; Berghaus et al., 2011). Additionally, the effects of DEX, GAMI and the combination of both drugs on the synthesis and release of TNF-\ensuremath{\alpha} and IL-6 will be studied in LPS-challenged pigs. Results and conclusions will be presented at the congress. 
References
Ferguson D.C., Dirikolu L., Hoenig M. (2009). Glucocorticoids, Mineralocorticoids, and Adrenolytic drugs. In Veterinary Pharmacology and Therapeutics, 9th Ed. Eds Riviere J.E., Papich M.G. Wiley-Blackwell, Iowa, USA, pp 771-802.
Kanoh S. and Rubin B.K. (2010). Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications. Clinical Microbiology Reviews, 23, 590-615.
Huang R.A., Letendre L.T., Banav N., Fischer J., Somerville B. (2011). Pharmacokinetics of gamithromycin in cattle with comparison of plasma and lung tissue concentrations and plasma antibacterial activity. Journal of Veterinary Pharmacology and Therapeutics, 33, 227-237.
Berghaus L.J., Gigu{\`e}re S., Sturgill T.L., Bade D., Malinski T.J., Huang R. (2012). Plasma pharmacokinetics, pulmonary distribution, and in vitro activity of gamithromycin in foals.  Journal of Veterinary Pharmacology and Therapeutics, 35, 59-65.},
  author       = {Wyns, Heidi and Meyer, Evelyne and Watteyn, Anneleen 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      = {bioavailability,pigs,pharmacokinetics,dexamethasone},
  language     = {eng},
  location     = {Noordwijkerhout, The Netherlands},
  title        = {Pharmacokinetics of dexamethasone in pigs},
  year         = {2012},
}

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