Predicting Drug Interaction of Clopidogrel on Microbial Metabolism of Diclofenac
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 chromatogra...
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| Veröffentlicht in: | Applied biochemistry and biotechnology 2010-03, Vol.160 (5), p.1508-1516 |
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| creator | Srisailam, K Raj Kumar, V Veeresham, C |
| description | 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. |
| doi_str_mv | 10.1007/s12010-009-8605-0 |
| format | Article |
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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.</description><identifier>ISSN: 0273-2289</identifier><identifier>EISSN: 1559-0291</identifier><identifier>DOI: 10.1007/s12010-009-8605-0</identifier><identifier>PMID: 19347265</identifier><identifier>CODEN: ABIBDL</identifier><language>eng</language><publisher>New York: New York : Humana Press Inc</publisher><subject>Biochemistry ; Bioconversions. Hemisynthesis ; Biological and medical sciences ; Biotechnology ; Biotransformation ; Chemistry ; Chemistry and Materials Science ; Chromatography ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Diclofenac - chemistry ; Diclofenac - metabolism ; Drug Interactions ; Drugs ; Fermentation ; Fundamental and applied biological sciences. Psychology ; Fungi ; Fungi - metabolism ; Liquid chromatography ; Mammals ; Mass Spectrometry ; Mass spectroscopy ; Metabolism ; Metabolites ; Methods. Procedures. 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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.</description><subject>Biochemistry</subject><subject>Bioconversions. Hemisynthesis</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Biotransformation</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Chromatography</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Chromatography, Liquid</subject><subject>Diclofenac - chemistry</subject><subject>Diclofenac - metabolism</subject><subject>Drug Interactions</subject><subject>Drugs</subject><subject>Fermentation</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fungi</subject><subject>Fungi - metabolism</subject><subject>Liquid chromatography</subject><subject>Mammals</subject><subject>Mass Spectrometry</subject><subject>Mass spectroscopy</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Methods. Procedures. 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| ispartof | Applied biochemistry and biotechnology, 2010-03, Vol.160 (5), p.1508-1516 |
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| subjects | Biochemistry Bioconversions. Hemisynthesis Biological and medical sciences Biotechnology Biotransformation Chemistry Chemistry and Materials Science Chromatography Chromatography, High Pressure Liquid Chromatography, Liquid Diclofenac - chemistry Diclofenac - metabolism Drug Interactions Drugs Fermentation Fundamental and applied biological sciences. Psychology Fungi Fungi - metabolism Liquid chromatography Mammals Mass Spectrometry Mass spectroscopy Metabolism Metabolites Methods. Procedures. Technologies Ticlopidine - analogs & derivatives Ticlopidine - metabolism Time Factors |
| title | Predicting Drug Interaction of Clopidogrel on Microbial Metabolism of Diclofenac |
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