University College of Pharmaceutical Sciences, Kakatiya University, Warangal 506009, Andra Pradesh, India.
Appl Biochem Biotechnol. 2010 Mar;160(5):1508-16. doi: 10.1007/s12010-009-8605-0. Epub 2009 Apr 4.
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.
为了阐明参与生物转化的酶的性质，研究了七种真菌培养物对双氯芬酸的代谢作用，因为双氯芬酸是哺乳动物细胞色素 P450（CYP）2C9 同工酶的特异性底物。通过高效液相色谱-二极管阵列检测和液相色谱-串联质谱分析鉴定了代谢物。该研究包括氯吡格雷，一种 CYP2C9 同工酶的选择性抑制剂，用于抑制双氯芬酸的代谢。采用两阶段发酵方案研究双氯芬酸的代谢及其被氯吡格雷抑制的情况。在所研究的培养物中，有四种显示出药物相互作用的阳性迹象，因为氯吡格雷以剂量依赖的方式抑制双氯芬酸的代谢。结果表明，微生物培养物具有类似于哺乳动物的酶系统，可用于预测哺乳动物系统中的药物相互作用。
