Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Biotransformation of Valdecoxib by Microbial Cultures

  • Srisailam, K. (University College of Pharmaceutical Sciences, Kakatiya University) ;
  • Veeresham, C. (University College of Pharmaceutical Sciences, Kakatiya University)
  • Received : 2009.10.21
  • Accepted : 2009.11.21
  • Published : 2010.04.28
Download PDF
⟨ Previous Next ⟩

Abstract

Microbial biotransformations can be used to predict mammalian drug metabolism. The present investigation deals with microbial biotransformation of valdecoxib using microbial cultures. Thirty-nine bacterial, fungal, and yeast cultures were used to elucidate the biotransformation pathway of valdecoxib. A number of microorganisms metabolized valdecoxib to various levels to yield nine metabolites, which were identified by HPLC-DAD and LC-MS-MS analyses. HPLC analysis of biotransformed products indicated that a majority of the metabolites are more polar than the substrate valdecoxib. Basing on LC-MS-MS analysis, the major metabolite was identified as a hydroxymethyl metabolite of valdecoxib, whereas the remaining metabolites were produced by carboxylation, demethylation, ring hydroxylation, N-acetylation, or a combination of these reactions. The hydroxymethyl and carboxylic acid metabolites were known to be produced in metabolism by mammals. From the results, it can be concluded that microbial cultures, particularly fungi, can be used to predict mammalian drug metabolism.

Keywords

References

  1. Abel, A. M., A. J. Carnell, J. A. Davis, and M. Paylor. 2003. The synthesis of buprenorphine intermediates by regioselective microbial N- and O-demethylation reactions using Cunninghamella echinulata NRRL 1384. Enzyme Microb. Technol. 33: 743-748. https://doi.org/10.1016/S0141-0229(03)00207-2
  2. Abourashed, E. A., A. M. Clark, and C. D. Hufford. 1999. Microbial models of mammalian metabolism of xenobiotics: An updated review. Curr. Med. Chem. 6: 359-374.
  3. Camu, F., T. Beecher, D. P. Recker, and K. M. Verburg. 2002. Valdecoxib, a COX-2 specific inhibitor, is an efficacious, opioid-sparing analgesic in patients undergoing hip arthroplasty. Am. J. Ther. 9: 43-51. https://doi.org/10.1097/00045391-200201000-00009
  4. Clark, A. M. and C. D. Hufford. 1991. Use of microorganisms for the study of drug metabolism - An update. Med. Res. Rev. 11: 473-501. https://doi.org/10.1002/med.2610110503
  5. Clark, A. M., J. D. McChesney, and C. D. Hufford. 1985. The use of microorganisms for the study of drug metabolism. Med. Res. Rev. 5: 231-253. https://doi.org/10.1002/med.2610050203
  6. Dodge, R. H., C. E. Cerniglia, and D. T. Gibson. 1979. Fungal metabolism of biphenyl. Biochem. J. 178: 223-230.
  7. Duhart, B. T., D. Zhang, J. Deck, J. P. Freeman, and C. E. Cerniglia. 1999. Biotransformation of protriptyline by filamentous fungi and yeasts. Xenobiotica 29: 733-746. https://doi.org/10.1080/004982599238353
  8. Ferris, J. P., M. J. Fasco, F. L. Stylianopoulou, D. M. Jerina, J. W. Daly, and A. M. Jeffrey. 1973. Monooxygenase activity in Cunninghamella bainieri: Evidence for a fungal system similar to liver microsomes. Arch. Biochem. Biophys. 156: 97-103. https://doi.org/10.1016/0003-9861(73)90345-7
  9. Foster, B. C., D. L. Wilson, and I. J. McGilveray. 1989. Effect of sparteine and quinidine on the metabolism of methoxyphenamine by Cunninghamella bainieri. Xenobiotica 19: 445-452. https://doi.org/10.3109/00498258909042285
  10. Foster, G. R., R. T. Coutts, F. M. Pasutto, and A. Mozayani. 1988. Microbial metabolism of phenelzine and pheniprazine. Life Sci. 42: 285-292. https://doi.org/10.1016/0024-3205(88)90637-6
  11. Foster, G. R., D. L. Lister, J. Zamecnic, and R. T. Coutts. 1991. The biotransformation of tranylcypromine by Cunninghamella echinulata. Can. J. Microbiol. 37: 791-795. https://doi.org/10.1139/m91-136
  12. Freitag, D. G., R. T. Foster, R. T. Coutts, M. A. Pickard, and F. M. Pasutto. 1997. Stereoselective metabolism of rac-mexiletine by the fungus Cunninghamella echinulata yields the major mammalian metabolites hydroxymethylmexiletine and p-hydroxymexiletine. Drug Metab. Dispos. 25: 685-692.
  13. Gessel, M., E. Hammer, M. Specht, W. Francke, and F. Schauer. 2001. Biotransformation of biphenyl by Paecilomyces lilacinus and characterization of ring cleavage products. Appl. Environ. Microbiol. 67: 1551-1557. https://doi.org/10.1128/AEM.67.4.1551-1557.2001
  14. Golbeck, J. H., S. A. Albaugh, and R. Radmer. 1983. Metabolism of biphenyl by Aspergillus toxicarius: Induction of hydroxylating activity and accumulation of water-soluble conjugates. J. Bacteriol. 156: 49-57.
  15. Hansen Jr., E. B., R. H. Heflich, W. A. Korfmacher, D. W. Miller, and C. E. Cerniglia. 1988. Microbial transformation of the antihistamine drug triprolidine hydrochloride. J. Pharm. Sci. 77: 259-264. https://doi.org/10.1002/jps.2600770316
  16. Harris, R. R., L. Black, S. Surapaneni, T. Kolasa, S. Majest, M. T. Namovic, et al. 2004. ABT-963 [2-(3,4-difluoro-phenyl)-4-(3-hydroxy-3-methyl-butoxy)-5-(4-methanesulfonyl-phenyl)-2H-pyridazin-3-one], a highly potent and selective disubstituted pyridazinone cyclooxgenase-2 inhibitor. J. Pharmacol. Exp. Ther. 311: 904-912. https://doi.org/10.1124/jpet.104.070052
  17. Huang, H., X. Yang, Q. Li, L. Sun, and D. Zhong. 2006. Biotransformation of tolbutamide to 4'-hydroxytolbutamide by the fungus Cunninghamella blakesleana. Appl. Microbiol. Biotechnol. 72: 486-491. https://doi.org/10.1007/s00253-005-0301-6
  18. Keshetty, S., R. K. Venisetty, V. Molmoori, and V. Ciddi. 2006. Determination of valdecoxib in serum using HPLC-diode array detector and its application in pharmacokinetic study. Pharmazie 61: 245-246.
  19. Mazier, C., M. Jaouen, M. Sari, and D. Buisson. 2004. Microbial oxidation of terfenadine and ebastine into fexofenadine and carebastine. Bioorg. Med. Chem. Lett. 14: 5423-5426. https://doi.org/10.1016/j.bmcl.2004.07.076
  20. Schwartz, H., A. Liebig-Weber, H. Hochstatter, and H. Bottcher. 1996. Microbial oxidation of ebastine. Appl. Microbiol. Biotechnol. 44: 731-735. https://doi.org/10.1007/BF00178610
  21. Smith, R. V., P. J. Davis, A. M. Clark, and S. Glover-Milton. 1980. Hydroxylation of biphenyl by fungi. J. Appl. Bacteriol. 49: 65-73. https://doi.org/10.1111/j.1365-2672.1980.tb01044.x
  22. Talley, J. J. 2000. Discovery of the second generation COX-2 inhibitor valdecoxib, p. 1. Abstr. 35th Midwest Regional Meeting of the American Chemical Society, St. Louis, Missouri.
  23. Talley, J. J., D. L. Brown, J. S. Carter, M. J. Graneto, C. M. Koboldt, J. L. Masferrer, et al. 2000. 4-[5-Methyl-3-phenylisoxazol-4-yl]-benzenesulfonamide, valdecoxib: A potent and selective inhibitor of COX-2. J. Med. Chem. 43: 775-777. https://doi.org/10.1021/jm990577v
  24. Talley, J. J., S. R. Bertenshaw, D. L. Brown, J. S. Carter, M. J. Graneto, M. S. Kellogg, et al. 2000. N-[[(5-Methyl-3-phenylisoxazol-4-yl)-phenyl]sulfonyl]propanamide, sodium salt, parecoxib sodium: A potent and selective inhibitor of COX-2 for parenteral administration. J. Med. Chem. 43: 1661-1663. https://doi.org/10.1021/jm000069h
  25. Venisetty, R. K., S. Keshetty, and V. Ciddi. 2004. Optimization of surfactants and polymers to alter the morphology of matt forming fungal cultures, an improved way for fungal drug metabolism studies, Abstr. PB-P005, p. 282. Abstr. 64th FIP Congress, International Pharmaceutical Federation, New Orleans, U.S.A.
  26. Vigne, B., A. Archelas, and R. Furstoss. 1991. Microbial transformations 18. Regiospecific para-hydroxylation of aromatic carbamate mediated by the fungus Beauveria sulfurescens. Tetrahedron 47: 1447-1458. https://doi.org/10.1016/S0040-4020(01)86421-8
  27. Wong, Y. W. J. and P. J. Davis. 1989. Microbial models of mammalian metabolism: Stereoselective metabolism of warfarin in the fungus Cunninghamella elegans. Pharm. Res. 6: 982-985. https://doi.org/10.1023/A:1015905832184
  28. Yuan, J. J., D. Yang, J. Y. Zhang, R. Bible Jr., A. Karim, and J. W. A. Findlay. 2002. Disposition of a specific cyclooxygenase-2 inhibitor, valdecoxib, in human. Drug Metab. Dispos. 30: 1013-1021. https://doi.org/10.1124/dmd.30.9.1013
  29. Zhang, D., H. Zhang, N. Aranibar, R. Hanson, Y. Huang, P. T. Cheng, et al. 2006. Structural elucidation of human oxidative metabolites of muraglitazar: Use of microbial bioreactors in the biosynthesis of metabolite standards. Drug Metab. Dispos. 34: 267-280.
  30. Zhang, J. Y., J. J. Yuan, Y. Wang, R. H. Bible Jr., and A. P. Breau. 2003. Pharmacokinetics and metabolism of a COX-2 inhibitor, valdecoxib, in mice. Drug Metab. Dispos. 31: 491-501. https://doi.org/10.1124/dmd.31.4.491

Cited by

  1. The Study of Different Approaches of Parecoxib Sodium Pretreatment on the Behavior of Rats with Neuropathic Pain vol.72, pp.1, 2010, https://doi.org/10.1007/s12013-014-0424-4