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Influence of administration route on the biotransformation of amoxicillin in the pig

Tim Reyns, Siska Croubels UGent, Sandra De Boever UGent, Stijn Schauvliege UGent, Frank Gasthuys UGent, Guylaine Meissonnier, Isabelle Oswald and Patrick De Backer UGent (2009) Journal of veterinary Pharmacology and Therapeutics. 32(3). p.241-248
abstract
A comparison was made in the plasma concentration of the major metabolites of amoxicillin (AMO), i.e. amoxicilloic acid (AMA) and amoxicillin diketopiperazine-2',5'-dione (DIKETO) in portal and jugular venous plasma after oral (p.o.) and intravenous (i.v.) AMO administration to pigs, in order to study a possible presystemic degradation of AMO in the gastro-intestinal tract and liver. Almost identical plasma concentration-time curves were obtained for AMO and its metabolites in portal and jugular venous plasma, both after p.o. and i.v. AMO administration. Almost immediately after i.v. AMO administration, high AMA and DIKETO concentrations were measured in plasma, while after p.o. dosing, the metabolites appeared in plasma after almost complete absorption of AMO. No significant differences in pharmacokinetic parameters of AMO, AMA and DIKETO, derived from the concentration-time profiles in portal and jugular venous plasma were calculated, both after i.v. and p.o. AMO administration (P > 0.05). After p.o. administration, the half-life of elimination (t(1/2(el))) for AMA is at least two or three times the t(1/2(el)) of AMO (0.75 h for AMO vs. 2.69 h for AMA), indicating the slower clearance of the metabolite. It could be hypothesized that AMA is only eliminated by glomerular filtration, as its open beta-lactam structure might not be recognized by the transport carrier in the proximal tubule of the kidney. The results of the study indicate that AMO is not substantially metabolized presystemically in the gut and liver. Therefore, it may be assumed that the kidney may be the major organ for AMO biotransformation. Future in vivo and in vitro experiments should be performed to state this hypothesis.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
PHARMACOKINETICS, AMPICILLIN, ABSORPTION, RAT, PENICILLINS, MAJOR METABOLITES, TANDEM MASS-SPECTROMETRY, CLAVULANIC ACID, ORAL BIOAVAILABILITY, BETA-LACTAM ANTIBIOTICS, analysis, pharmacokinetics, amoxicillin, biotransformation, pig
journal title
Journal of veterinary Pharmacology and Therapeutics
J. Vet. Pharmacol. Ther.
volume
32
issue
3
pages
241 - 248
Web of Science type
article
Web of Science id
000266180600006
JCR category
VETERINARY SCIENCES
JCR impact factor
1.408 (2009)
JCR rank
36/141 (2009)
JCR quartile
2 (2009)
ISSN
0140-7783
DOI
10.1111/j.1365-2885.2008.01033.x
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
977513
handle
http://hdl.handle.net/1854/LU-977513
alternative location
http://www3.interscience.wiley.com/cgi-bin/fulltext/121500189/PDFSTART
date created
2010-06-11 17:41:35
date last changed
2010-07-01 11:22:50
@article{977513,
  abstract     = {A comparison was made in the plasma concentration of the major metabolites of amoxicillin (AMO), i.e. amoxicilloic acid (AMA) and amoxicillin diketopiperazine-2',5'-dione (DIKETO) in portal and jugular venous plasma after oral (p.o.) and intravenous (i.v.) AMO administration to pigs, in order to study a possible presystemic degradation of AMO in the gastro-intestinal tract and liver. Almost identical plasma concentration-time curves were obtained for AMO and its metabolites in portal and jugular venous plasma, both after p.o. and i.v. AMO administration. Almost immediately after i.v. AMO administration, high AMA and DIKETO concentrations were measured in plasma, while after p.o. dosing, the metabolites appeared in plasma after almost complete absorption of AMO. No significant differences in pharmacokinetic parameters of AMO, AMA and DIKETO, derived from the concentration-time profiles in portal and jugular venous plasma were calculated, both after i.v. and p.o. AMO administration (P {\textrangle} 0.05). After p.o. administration, the half-life of elimination (t(1/2(el))) for AMA is at least two or three times the t(1/2(el)) of AMO (0.75 h for AMO vs. 2.69 h for AMA), indicating the slower clearance of the metabolite. It could be hypothesized that AMA is only eliminated by glomerular filtration, as its open beta-lactam structure might not be recognized by the transport carrier in the proximal tubule of the kidney. The results of the study indicate that AMO is not substantially metabolized presystemically in the gut and liver. Therefore, it may be assumed that the kidney may be the major organ for AMO biotransformation. Future in vivo and in vitro experiments should be performed to state this hypothesis.},
  author       = {Reyns, Tim and Croubels, Siska and De Boever, Sandra and Schauvliege, Stijn and Gasthuys, Frank and Meissonnier, Guylaine and Oswald, Isabelle and De Backer, Patrick},
  issn         = {0140-7783},
  journal      = {Journal of veterinary Pharmacology and Therapeutics},
  keyword      = {PHARMACOKINETICS,AMPICILLIN,ABSORPTION,RAT,PENICILLINS,MAJOR METABOLITES,TANDEM MASS-SPECTROMETRY,CLAVULANIC ACID,ORAL BIOAVAILABILITY,BETA-LACTAM ANTIBIOTICS,analysis,pharmacokinetics,amoxicillin,biotransformation,pig},
  language     = {eng},
  number       = {3},
  pages        = {241--248},
  title        = {Influence of administration route on the biotransformation of amoxicillin in the pig},
  url          = {http://dx.doi.org/10.1111/j.1365-2885.2008.01033.x},
  volume       = {32},
  year         = {2009},
}

Chicago
Reyns, Tim, Siska Croubels, Sandra De Boever, Stijn Schauvliege, Frank Gasthuys, Guylaine Meissonnier, Isabelle Oswald, and Patrick De Backer. 2009. “Influence of Administration Route on the Biotransformation of Amoxicillin in the Pig.” Journal of Veterinary Pharmacology and Therapeutics 32 (3): 241–248.
APA
Reyns, T., Croubels, S., De Boever, S., Schauvliege, S., Gasthuys, F., Meissonnier, G., Oswald, I., et al. (2009). Influence of administration route on the biotransformation of amoxicillin in the pig. Journal of veterinary Pharmacology and Therapeutics, 32(3), 241–248.
Vancouver
1.
Reyns T, Croubels S, De Boever S, Schauvliege S, Gasthuys F, Meissonnier G, et al. Influence of administration route on the biotransformation of amoxicillin in the pig. Journal of veterinary Pharmacology and Therapeutics. 2009;32(3):241–8.
MLA
Reyns, Tim, Siska Croubels, Sandra De Boever, et al. “Influence of Administration Route on the Biotransformation of Amoxicillin in the Pig.” Journal of veterinary Pharmacology and Therapeutics 32.3 (2009): 241–248. Print.