Abstract
Seven fungal cultures were studied for the metabolism of diclofenac in order to elucidate the nature of enzymes involved in biotransformation, as diclofenac is a specific substrate to cytochrome P450 (CYP) 2C9 isozyme in mammals. The metabolites were identified by high-performance liquid chromatography–diode array detection and liquid chromatography–tandem mass spectroscopy analysis. The study included clopidogrel, a selective inhibitor of CYP2C9 isozyme, to inhibit the metabolism of diclofenac. Two-stage fermentation protocol was used to study the diclofenac metabolism and its inhibition by clopidogrel. Among the cultures studied, four have shown positive indication for drug interaction, since clopidogrel inhibited the metabolism of diclofenac in a dose-dependent manner. The results indicate that microbial cultures possess enzyme systems similar to mammals and they can be used to predict drug interactions in mammalian systems.
Similar content being viewed by others
References
Davies, N. M., & Anderson, K. E. (1997). Clinical Pharmacokinetics, 33, 184–213. doi:10.2165/00003088-199733030-00003.
Leeman, T., Transon, C., & Dayer, P. (1993). Life Sciences, 52, 29–34. doi:10.1016/0024-3205(93)90285-B.
Bort, R., Mace, K., Boobis, A., Gomez-Lechon, M. J., Pfeifer, A., & Castell, J. (1999). Biochemical Pharmacology, 58, 787–796. doi:10.1016/S0006-2952(99)00167-7.
Shen, S., Marchick, M. R., Davis, M. R., Doss, G. A., & Pohl, L. R. (1999). Chemical Research in Toxicology, 12, 214–222. doi:10.1021/tx9802365.
Tang, W., Stearns, R. A., Wang, R. W., Chiu, S. H., & Baillie, T. A. (1999). Chemical Research in Toxicology, 12, 192–199. doi:10.1021/tx9802217.
Ibrahim, A. R. S., & El-Feraly, F. S. (1996). Saudi Pharmaceutical Journal, 4, 165–169.
Webster, R., Pacey, M., Winchester, T., Johnson, P., & Jezequel, S. (1998). Applied Microbiology and Biotechnology, 49, 371–376. doi:10.1007/s002530051184.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Srisailam, K., Raj Kumar, V. & Veeresham, C. Predicting Drug Interaction of Clopidogrel on Microbial Metabolism of Diclofenac. Appl Biochem Biotechnol 160, 1508–1516 (2010). https://doi.org/10.1007/s12010-009-8605-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12010-009-8605-0