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

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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.
Keywords
PHARMACOKINETICS, AMPICILLIN, ABSORPTION, RAT, PENICILLINS, MAJOR METABOLITES, TANDEM MASS-SPECTROMETRY, CLAVULANIC ACID, ORAL BIOAVAILABILITY, BETA-LACTAM ANTIBIOTICS, analysis, pharmacokinetics, amoxicillin, biotransformation, pig

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MLA
Reyns, Tim 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.
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.
Chicago author-date
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.
Chicago author-date (all authors)
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.
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.
IEEE
[1]
T. Reyns et al., “Influence of administration route on the biotransformation of amoxicillin in the pig,” Journal of veterinary Pharmacology and Therapeutics, vol. 32, no. 3, pp. 241–248, 2009.
@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 > 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},
  keywords     = {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},
}

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