Delatour P, Garnier F, Maire R
Département de Toxicologie Métabolique, Ecole Nationale Vétérinaire de Lyon.
Bull Acad Natl Med. 1996 Oct;180(7):1565-72.
After administration of the racemic drug, the stereoselective quantification of the enantiomers of free and conjugated carprofen was performed in human plasma and in plasma, urine and bile of dogs and horses. In humans, the plasma profile of free carprofen and its glucuronides is not stereoselective and the glucuronides excreted in urine are close to a racemate. In dogs and horses on the contrary, the R(-) enantiomer of the free drug is predominant in plasma, while urine and/or bile concentrations of the glucuronides are high in comparison to plasma with a strong selectivity for the S(+) enantiomer. Because glucuronidation of carprofen, as a carboxylic compound, is known to be the major metabolic pathway in most species, interspecies discrepancies in the stereoselective disposition of carprofen seem to be mainly related to the stereoselectivity in the excretion of the glucuronides. Finally, the high plasma concentrations of carprofen glucuronides in human in comparison to other animal species suggest that the former could be specifically subjected to immunological side effects in the time course of treatments by this type of compounds.
给予消旋药物后，在人血浆以及犬和马的血浆、尿液和胆汁中对游离和结合型卡洛芬对映体进行了立体选择性定量分析。在人体中，游离卡洛芬及其葡萄糖醛酸苷的血浆分布没有立体选择性，尿液中排泄的葡萄糖醛酸苷接近外消旋体。相反，在犬和马中，游离药物的R(-)对映体在血浆中占主导地位，而与血浆相比，葡萄糖醛酸苷在尿液和/或胆汁中的浓度较高，且对S(+)对映体具有很强的选择性。由于卡洛芬作为一种羧酸化合物，其葡萄糖醛酸化是大多数物种的主要代谢途径，卡洛芬立体选择性处置的种间差异似乎主要与葡萄糖醛酸苷排泄的立体选择性有关。最后，与其他动物物种相比，人体中卡洛芬葡萄糖醛酸苷的血浆浓度较高，这表明在这类化合物的治疗过程中，人体可能会特别受到免疫副作用的影响。
