[Enantioselectivity in the excretion of glucuronides of carprofen in man, dogs and horses].

The study explores the differences in the way a drug called carprofen, used commonly for pain relief in veterinary medicine, is metabolized and excreted by humans, dogs, and horses. It is found that the free carprofen isn’t biased towards a specific form in humans, but dogs and horses show a preference for the R(-) form. The differences in excretion between species suggest potential species-specific side effects, especially for humans who may experience immunological side effects.

Study Objectives and Methodology

• The study focuses on the metabolization and excretion of a drug, carprofen, in several species, namely humans, dogs, and horses.
• The testing method involved the administration of the racemic drug (substance containing equal amounts of left and right-handed enantiomers of a chiral molecule) and the subsequent examination of the enantiomers of free and conjugated carprofen in the plasma, urine, and bile of the test subjects.

Results

• The researchers found that the plasma concentration of both free carprofen and its glucuronides in humans is not stereoselective, i.e., it doesn’t show a bias towards either form.
• The glucuronides excreted in the human urine closely match a racemate, which means they contain equal amounts of left and right-handed enantiomers.
• Contrastingly, in dogs and horses, the R(-) enantiomer of the free drug is predominant in plasma. Furthermore, the concentration of the glucuronides in urine and/or bile is comparatively high with a significant selectivity for the S(+) enantiomer.

Implications

• The glucuronidation of carprofen, a carboxylic compound, is known to be a major metabolic pathway in many species.
• Therefore, significant inconsistencies in the stereoselective disposition of carprofen across species are primarily attributed to the differential excretion of the glucuronides.
• The relatively high plasma concentrations of carprofen glucuronides in humans suggest that humans could specifically be at risk of immunological side effects when treated with such compounds.