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Chiral Inversion of (R)-Ketoprofen: Influence of Age and Differing Physiological Status in Dairy Cattle

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Abstract

The chiral inversion of ketoprofen has been previously demonstrated in cattle, but no studies have been performed on different ages and metabolic situations in the animals. The aim of this work was to study any modifications of the stereoconversion of ketoprofen that occur by reason of age, lactation or gestation in dairy cows. Holando Argentino cattle were divided into three groups: 8 cows in early lactation, 8 pregnant cows and 8 newborn calves. Four animals from each group received the enantiomer R-(−)-ketoprofen by intravenous administration; the other four animals received the S-(+) enantiomer, all at doses of 0.5 mg/kg. Blood samples were collected at standardized times after dosing and assayed for ketoprofen by high-performance reversed-phase liquid chromatography (HPLC). The percentage inversion of R-(−)-ketoprofen to S-(+)-ketoprofen was 50.5% (SD ± 2.4) in the preruminants, 33.3% (SD ± 1.7) in cows in early lactation and 26.0% (SD ± 5.1) in cows in gestation. These results indicate a differing enantioselective metabolic behaviour for one compound in one species under different physiological situations.

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REFERENCES

  • Aberg, G., Ciofalo, V.B. and Pendleton, R., 1995. Inversion of R to S ketoprofen in eight animal species. Chirality, 7, 383-387

    Google Scholar 

  • Baggot, D., 1977. Principles of drug disposition in domestic animals. In: The Basics of Veterinary Clinical Pharmacology, (WB Saunders, Philadelphia), 144-189

    Google Scholar 

  • Bauchart, D., Gruffat, D. and Durand, D., 1996. Lipid absorption and hepatic metabolism in ruminants. Proceedings of the Nutrition Society, 55, 39-47

    Google Scholar 

  • Browne, G.S., Nelson, C., Nguyen, T., Ellis, B.A., Day, R.O. and Williams, K.M., 1999. Stereoselective and substrate-dependent inhibition of hepatic mitochondrial β-oxidation and oxidative phosphorylation by the non-steroidal anti-inflammatory drugs ibuprofen, flurbiprofen and ketorolac. Biochemical Pharmacology, 57, 837-844

    Google Scholar 

  • Carabaza, A., Suesa, N., Tost, D., Pascual, J., Gomez, M., Gutierrez, M., Ortega, E., Montserrat, X., Garcia, A.M., Mis, R., Cabre, F., Mauleon, D. and Carganico, G., 1996. Stereoselective metabolic pathways of ketoprofen in the rat: incorporation into triacylglycerols and enantiomeric inversion. Chirality, 8, 163-172

    Google Scholar 

  • Caldwell, J. and Marsh, M.V., 1983. Interrelationships between xenobiotic metabolism and lipid biosynthesis. Biochemical Pharmacology, 32, 1667-1672

    Google Scholar 

  • Caldwell, J., Hutt, A.J. and Fournel-Gigleux, S., 1988. The metabolic chiral inversion and dispositional enantioselectivity of the 2-arylpropionic acids and their biological consequences. Biochemical Pharmacology, 37, 105-114

    Google Scholar 

  • Chilliard, Y., 1987. Revue Bibliograhique: Variations quantitatives et mètabolisme des lipides dans les tissus adipeux et le foie au cours du cycle gestation-lactation. 2e partie: chez la brebis et la vache. Reproduction Nutrition et Dévéloppement, 27, 327-398

    Google Scholar 

  • Chilliard, Y., Morand-Fehr, P., Sauvant, D. and Bas, P., 1986. Utilisation métabolique des lipides par le ruminant en lactation. Bulletin de Technologie CRZV Theix InRA, 63, 81-91

    Google Scholar 

  • Cox, J.W., Cox, S.R., Vangiessen, G. and Ruwart, M.J., 1985. Ibuprofen stereoisomer hepatic clearance and distribution in normal and fatty in situ perfused rat liver. Journal of Pharmacology and Experimental Therapeutics, 232, 636-6443

    Google Scholar 

  • DeGraves, F.J., Riddell, M. and Schumacher, J., 1996. Ketoprofen concentrations in plasma and milk after intravenous administration in dairy cattle. American Journal of Veterinary Research, 57, 1031-1033

    Google Scholar 

  • Dodds, P.F., 1995. Xenobiotic lipids: the inclusion of xenobiotic compounds in pathways of lipid biosynthesis. Progress in Lipid Research, 34, 219-247

    Google Scholar 

  • Fears R, Baggaley, K.H., Alexander, R., Morgan, B. and Hindley, R.M., 1978. The participation of ethyl 4-benzoate (BRL 10894) and other aryl-substituted acids in glycerolipid metabolism. Journal of Lipid Research, 19, 3-11

    Google Scholar 

  • Foster, R.T. and Jamali, F., 1987. High performance chromatographic assay of ketoprofen enantiomers in human plasma and urine. Journal of Chromatography, 416, 338-393

    Google Scholar 

  • Grummer, R.R., 1992. Etiology of lipid-related metabolic disorders in periparturient dairy cows. Journal of Dairy Science, 76, 3882-3896

    Google Scholar 

  • Hall, S.D., Hassanzadeh-Khayyat, M., Knalder, M.P. and Mayer, P.R., 1992. Pulmonary inversion of 2-arylpropionic acids: influence of protein binding. Chirality, 4, 349-352

    Google Scholar 

  • Holstenius, P. and Holstenius, K., 1996. New aspects of ketone bodies in energy metabolism of dairy cows. A review. Journal of the Veterinary Medical Association, 43, 579-587

    Google Scholar 

  • Hutt, A.J. and Caldwell, J., 1990. Amino acid conjugation. In: G.J. Mulder (ed.), Conjugation Reactions in Drug Metabolism, (Taylor and Francis, London), 273-305

    Google Scholar 

  • Jamali, F., 1988. Pharmacokinetics of enantiomers of chiral non-steroidal anti-inflammatory drugs. European Journal of Drug Metabolism, 13, 1-9

    Google Scholar 

  • Jeffrey, P., Tucker, G.T., Bye, A., Crewe, H.K. and Wright, P.A., 1991. The site of inversion of R-(−)-ibuprofen: studies using rat in situ perfused rat liver. Journal of Pharmacy and Pharmacology, 43, 715-720

    Google Scholar 

  • Knights, K.M., 1998. Role of hepatic fatty acid:coenzyme a ligases in the metabolism of xenobiotic carboxylic acids. Clinical and Experimental Pharmacology and Physiology, 25, 776-782

    Google Scholar 

  • Knights, K.M., Talbot, U.M. and Baillie, T.A., 1992. Evidence of multiple forms of rat liver microsomal coenzyme A ligase catalysing the formation of 2-arylpropionyl-coenzyme A thioesters. Biochemical Pharmacology, 44, 2415-2417

    Google Scholar 

  • Landoni, M.F., Cunningham, F.M. and Lees, P., 1995. Pharmacokinetics and pharmacodynamics of ketoprofen in calves applying PK/PD modelling. Journal of Veterinary Pharmacology and Therapeutics, 18, 315-324

    Google Scholar 

  • Mauleón, D., Artigas, R., Garcia, M.L. and Carganico, G., 1996. Preclinical and clinical development of dexketoprofen. Drugs, 52(supplement 5), 24-46

    Google Scholar 

  • Mayer, J.M., 1990. Stereoselective metabolism of anti-inflammatory 2-arylpropionates. Acta Pharmacologica Nordica, 2, 197-216

    Google Scholar 

  • Mayer, J.M., Roy-De Vos, M., Audergon, C., Testa, B. and Etter, J.C., 1994. Interactions of anti-inflammatory 2-arylpropionates (profens) with the metabolism of fatty acids: in vitro studies. International Journal of Tissue Reactions — Experimental and Clinical Aspects, 16, 59-72

    Google Scholar 

  • Mehvar, R. and Jamali, F., 1988. Pharmacokinetic analysis of enantiomeric inversion of chiral nonsteroidal anti-inflammatory drugs. Pharmaceutical Research, 5, 76-79

    Google Scholar 

  • Menzel, S., Waibel, R., Brune, K. and Geisslinger, G., 1994. Is the formation of R-ibuprophenyl-adenylate the first stereoselective step in chiral inversion? Biochemical Pharmacology, 48, 1056-1058

    Google Scholar 

  • Nakamura, Y., Yamaguchi, T. and Takahashi, S., 1981. Optical isomerisation mechanism of R (−) hydratropic acid derivatives. Journal of Pharmacobio Dynamics, 4, S-1

    Google Scholar 

  • Pang, K.S. and Kwan, K.C., 1983. A commentary: methods and assumptions in the kinetic estimation of metabolite formation. Drug Metabolism and Disposition, 11, 79-84

    Google Scholar 

  • Sallustio, B.C., Meffin, P.J. and Knights, M., 1988. The stereospecific incorporation of fenoprofen into rat hepatocyte and adipocyte triacylglicerols. Biochemical Pharmacology, 37, 1919-1923

    Google Scholar 

  • Schoonjans, K., Staels, B., Grimaldi, P. and Auwerx, J., 1993. Acyl-CoA synthetase nRNA expression is controlled by fibric, feeding and liver proliferation. European Journal of Biochemistry, 216, 615-622

    Google Scholar 

  • Shirley, M., Guan, X., Kaise, D., Halsted, G.W. and Baillie, T.A., 1994. Taurine conjugation of ibuprofen in human and rat liver in vitro. Relationship to metabolic chiral inversion. Journal of Pharmacology and Experimental Therapeutics, 269, 1166-1175

    Google Scholar 

  • Soraci, A. and Benoit, E., 1995. In vitro fenoprophenyl-coenzyme A thioester formation: interspecies variations. Chirality, 7, 534-540

    Google Scholar 

  • Soraci, A., Benoit, E. and Delatour, P., 1995. Comparative metabolism of R(−)-fenoprofen in rats and sheep. Journal of Veterinary Pharmacology and Therapeutics, 18, 1-5

    Google Scholar 

  • Soraci, A., Jaussaud, P., Benoit, E. and Delatour, P., 1996. Chiral inversion of fenoprofen in horses and dogs: an in vivo-in vitro study. Veterinary Research, 27, 13-22

    Google Scholar 

  • Sukuzi, W., Kawarabyasi, Y.U., Kondo, T., Abe, K., Nishikawa, K., Kimura, S., Hashimoto, T. and Yamamoto, T., 1990. Structure and regulation of rat long-chain acid-CoA synthetase. Journal of Biological Chemistry, 265, 8681-8685

    Google Scholar 

  • Tanaka, Y., Shimomura, Y., Hirota, T., Nozaki, A., Ebata, M., Takasaky, W., Sigehara, E., Hayashi, R. and Caldwell, J., 1992. Formation of glycine conjugate and (−) and (+) enantiomers from (+)-(S)-2-phenylpropionic acid suggesting the formation of the CoA thioester intermediate in dogs. Chirality, 4, 342-348

    Google Scholar 

  • Williams, K.M., Day, R.O., Knihinicki, R.D. and Duffield, A., 1986. The stereoselective uptake of ibuprofen enantiomers into adipose tissue. Biochemical Pharmacology, 35, 3403-3405

    Google Scholar 

  • Zhao, B., Geisslinger, G., Hall, I., Day, R.O. and Williams, K.M., 1992. The effect of the enantiomers of ibuprofen and flurbiprofen on the beta-oxidation of palmitate in the rat. Chirality, 4, 137-141

    Google Scholar 

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Igarza, L., Soraci, A., Auza, N. et al. Chiral Inversion of (R)-Ketoprofen: Influence of Age and Differing Physiological Status in Dairy Cattle. Vet Res Commun 26, 29–37 (2002). https://doi.org/10.1023/A:1013301620904

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