Enantioselective glucuronidation and subsequent biliary excretion of carprofen in horses.
Abstract: Carprofen (CPF) enantiomers and their glucuronide conjugates (GLUC) were measured in plasma and bile of horses after IV administration of the racemic compound (0.7 mg/kg of body weight). The CPF was detectable in plasma for up to 72 hours after dosing, whereas GLUC appeared early (time for maximal plasma concentration, 1 hour) and was measurable transiently at low concentration (maximal plasma concentration, 0.5 microgram/ml). The enantiospecific plasma profiles indicated a clear predominance of R-CPF, whereas the stereoselectivity of the glucuronides favored S-GLUC. At 1, 2, and 12 hours after administration of the drug, bile concentrations of GLUC were high compared with those in plasma and enantioselectivity favored S-GLUC. These data indicate that the higher body clearance observed for S-CPF is a consequence of the enantioselectivity in liver glucuronidation and subsequent biliary excretion of the S enantiomer of the drug.
Publication Date: 1995-03-01 PubMed ID: 7771704
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research study explores the process of enantioselective glucuronidation and subsequent biliary excretion of carprofen, a common veterinary drug, in horses. The key finding is that the higher body clearance for one type of the drug’s molecule (S-CPF) is due to the enantioselectivity in liver glucuronidation and subsequent biliary excretion.
Research Methodology
- The researchers measured the presence of Carprofen (CPF) enantiomers and their glucuronide conjugates (GLUC) in the plasma and bile of horses, after intravenous administration of the racemic compound. This compound was administered at a rate of 0.7 mg/kg of the horse’s body weight.
- The CPF was monitored in the plasma over time, specifically for up to 72 hours after dosage.
- The appearance and concentration of GLUC was also observed and measured in the plasma. The time for maximal plasma concentration was 1 hour after dosage, and the maximal plasma concentration reached was 0.5 microgram/ml.
Key Findings
- The enantiospecific plasma profiles revealed a clear predominance of one kind of CPF enantiomer, R-CPF; the stereoselectivity of the glucuronides instead favored another, S-GLUC.
- At 1, 2, and 12 hours after the drug’s administration, bile concentrations of GLUC were high in comparison to the plasma concentrations, with enantioselectivity favoring S-GLUC.
- The higher body clearance of S-CPF, as observed in the study, is attributed to the enantioselective process of liver glucuronidation and subsequent biliary excretion of the S enantiomer of the drug.
Significance of the Research
- This research validates the enantioselective process by which carprofen is metabolized in horses’ bodies.
- The findings can help to understand how to optimize the use of the drug for better efficacy, by considering the enantioselectivity in the production of the glucuronides and their subsequent excretion.
- The study further highlights the importance of considering the chiral nature of pharmaceutical drugs in veterinary medicine.
Cite This Article
APA
Soraci A, Benoit E, Jaussaud P, Lees P, Delatour P.
(1995).
Enantioselective glucuronidation and subsequent biliary excretion of carprofen in horses.
Am J Vet Res, 56(3), 358-361.
Publication
Researcher Affiliations
- Department of Basic Sciences and Clinical Biology, School of Veterinary Medicine of Lyon, Marcy-l'Etoile, France.
MeSH Terms
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / metabolism
- Bile / metabolism
- Carbazoles / blood
- Carbazoles / metabolism
- Glucuronates / blood
- Glucuronates / metabolism
- Horses / blood
- Horses / metabolism
- Male
- Stereoisomerism
Citations
This article has been cited 4 times.- Guo CC, Tang YH, Hu HH, Yu LS, Jiang HD, Zeng S. Analysis of chiral non-steroidal anti-inflammatory drugs flurbiprofen, ketoprofen and etodolac binding with HSA. J Pharm Anal 2011 Aug;1(3):184-190.
- Ingrao JC, Johnson R, Tor E, Gu Y, Litman M, Turner PV. Aqueous stability and oral pharmacokinetics of meloxicam and carprofen in male C57BL/6 mice. J Am Assoc Lab Anim Sci 2013 Sep;52(5):553-9.
- Lees P. Pharmacology of drugs used to treat osteoarthritis in veterinary practice. Inflammopharmacology 2003;11(4):385-99.
- Akyol BA, Gokbulut C. The effect of intravenous lipid emulsion (ILE) on the pharmacokinetic/toxicokinetic dispositions of ivermectin and carprofen in rabbits. Naunyn Schmiedebergs Arch Pharmacol 2024 Mar;397(3):1841-1852.
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