Summar
(R)-(−)-benoxaprofen is stereospecifically inverted to the (S)-( + )-enantiomer by rats and humans. The rate of inversion is much faster in rats (t1/2ca. 2.5 h) than in humans (t1/2 108 h). Inversion in rats apparently does not occur in the liver, but can be brought about in vitro by an everted intestinal sac preparation, suggesting that the transformation takes place while passing through the gut wall.
Similar content being viewed by others
References
Cashin CH., Dawson W. and Kitchen E.A. (1977): The pharmacology of benoxaprofen (2-(4-chlorophenyl)-α-methyl-5-benzoxazole acetic acid), LRCL 3794, a new compound with anti-inflammatory activity apparently unrelated to inhibition of prostaglandin synthesis, J. Pharm. Pharmacol.,29, 330–336.
Chatfield D.H. and Green J.N. (1978): Disposition and metabolism of benoxaprofen in laboratory animals and man, Xenobiotica,8, 133–144.
Evans D., Kitchen E.A., Meacock. S.C.R. and Williamson W.R.N.: Comparison of the anti-inflammatory activities of the racemate and enantiomers of benoxaprofen in rats, J. Pharm., Pharmacol., submitted for publication.
Bopp R.J., Nash J.F., Ridolfo A.S. and Shephard E.R.: Stereoselective inversion of (R)-(−)-benoxaprofen to the (S)-( + )-enantiomer in humans, Drug Metab. Disp., submitted for publication.
Kripalani K.J., El-Abdin A.Z., Dean A.V. and Schreiber E.C. (1976): Stereospecific inversion of 1-α-methylfluorene-2-acetic acid to its d-enantiomer in the dog, Xenobiotica,6, 159–169.
Lan S.J., Kripalani K.J., Dean A.V., Egli P., Difazio L.T. and Schreiber, E.C. (1976): Inversion of optical configuration of α-methylfiuorene-2-acetic acid (cicloprofen) in rats and monkeys, Drug Metab. Disp.,4, 330–339.
Wechter W.J., Loughhead D.G., Reischer, R.J., Van Geissena, G.J. and Kaiser, D.G. (1974): Enzymatic inversion at saturated carbon: nature and mechanism of the inversion of (R)-(−)-p-isobutyl-hydratropic acid, Biochem. Biophys. Res. Comm.,61, 833–837.
Kaiser D.G., Van Geissen G.J., Reischer R.J. and Wechter W.J. (1976): Isomeric inversion of ibuprofen (R)-enantiomer in humans, J. Pharm. Sci.,65, 269–273.
McKay S.W., Mallen D.N.B., Shrubsall P.R., Swann B.P. and Williamson W.R.N. (1979): Analysis of benoxaprofen and other α-methylaryl acetic acids using high performance liquid chromatography, J. Chromotogr.,170, 482–485.
Brewster D., Jones R.S. and Parke D.V. (1978): The metabolism of shikimate in the rat, Biochem. J.,170, 257–264.
Chatfield D.H. and Woodage T.J. (1978): Determination of benoxaprofen (2-(4-chlorophenyl)-α-methyl-5-benzoxazoleacetic acid, LRCL 3794) in biological fluids, J. Chromatogr.,153, 101–106.
Souter R.W. (1976): High performance liquid chromatographic separation of enantiomeric amines, Chromatographic,9, 635–637.
Smith G.L., Goubourn R.A., Burt R.A.P. and Chatfield D.H. (1977): Preliminary studies of absorption and excretion of benoxaprofen in man, Br. J. Clin. Pharmac,4, 585–590.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Simmonds, R.G., Woodage, T.J., Duff, S.M. et al. Stereospecific inversion of (R)-(−)-benoxaprofen in rat and man. European Journal of Drug Metabolism and Pharmacokinetics 5, 169–172 (1980). https://doi.org/10.1007/BF03189461
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03189461