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??This paper presents a review of the change of cytochrome P450 2C(CYP2C) in human development process and the effect of its gene polymorphism on clinical medication.The relevant literature at home and abroad was reviewed, analyzed, and summarized. The expression and activity of CYP2C9 and CYP2C19 enzymes are different at different ages, which has a direct effect on clinical drug use in pediatric patients. It has vital significance to further research the change rules of CYP2C9 and CYP2C19 and the influence of gene polymorphism on drug metabolism in the process of development for improving the efficacy and rationality of pediatric medication.     

精准医疗模式下群体药代动力学的优势及其在中医药领域中的应用探析

精准医疗是以基因组信息为基础的个体化治疗,为患者量身设计出最佳治疗方案,以期达到治疗效果最大化和副作用最小化的医疗模式。群体药代动力学研究可根据患者的个体差异制定个体化给药剂量,在精准医疗模式下具有独特的优势。目前,中药存在不良反应逐年增高等安全性问题,将基于精准医疗的群体药代动力学引入中医药领域非常必要。但因中药与化学药物不同,具有多成分的特点,需将群体药代动力学、遗传学与统计学方法相结合,制定符合中药特色的研究方法。关键科学问题是需明确对中药有效成分代谢有影响的药物代谢酶基因型,并注意分析具有多态性的药物代谢酶在人体中的整体作用趋势。明确关键科学问题,突破瓶颈,从而实现中医药的精准医疗,走向国际化。     

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??Antitumor drugs have the characteristics of low therapeutic index, narrow safety window, and so on, which are prone to have toxic and side effects in the course of clinical therapy, thus limiting their use. In recent years, some studies have pointed out that the mechanism of adverse reactions of antitumor drugs is related to drug metabolism enzymes, receptors and transporters. Among them, drug metabolism enzymes and their gene polymorphisms play an important role in the toxic and side effects of antitumor drugs. In this paper, we analyze and summarize the side effects of antitumor drugs mediated by drug metabolism enzymes, mainly from the aspects of the roles of metabolic enzymes and their gene polymorphism in the metabolic activation and metabolic detoxification of antitumor drugs, in order to effectively avoid or reduce the toxic side effects of antitumor drugs, and to provide a reference for individualized treatment of cancer.     

活血化瘀药物及其有效成分对生物转化酶的影响

生物转化酶在众多中西药物代谢中起着非常重要的作用。文章综述了近年来国内外学者就活血化瘀药物对生物转化酶影响的研究思路、方法和进展。通过深入研究活血化瘀药物对生物转化酶的影响,有利于中药基础理论的深入和发展;临床上应该重视活血化瘀药物与其他药物合用时所发生的代谢性相互作用,优化给药方案,从而提高临床用药的有效性和安全性。     

石榴叶鞣质与菠萝叶酚对哺乳期小鼠生长的比较

目的:观察石榴叶鞣质和菠萝叶酚通过母乳对哺乳期小鼠生长的影响。方法:给母鼠灌胃不同剂量的药物,观察新生小鼠的一般状况、体质量、尾长及脏器系数肝脏相关脂代谢调控因子的表达。结果:石榴叶鞣质和菠萝叶酚均可以通过母乳明显影响新生小鼠的生长发育,其中石榴叶鞣质的作用强于菠萝叶酚,同时可以明显下调新生小鼠肝脏的脂代谢相关酶的表达。结论:石榴叶鞣质和菠萝叶酚可以通过母乳影响新生小鼠的生长发育,其作用与影响肝脏脂代谢酶表达有关。哺乳期服用该药需引起注意。其临床意义尚有待于深入研究。     

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??This paper reviewed benefit and risk of myopathy and rhabdomyolysis in statins with guide and following the medical evidence.The chemical structure of statins is closely related to the effect and heterogeneity of the drugs. The use of statins including atorvastatin,rosuvastatin can give patients more clinical benefit when strengthen to low blood lipid. Although rosuvastatin in statins is strongest, but presence of sulphonamide group resulted in the increase of its toxicity, It show that rosuvastatin risk for rhabdomyolysis was significantly higher than that of atorvastatin statins by foreign evidence. Therefore, the patients following with multiple risk factors need to use caution with the choice of rosuvastatin. Recently rosuvastatin causing myopathy and rhabdomyolysis cases in the world has increased, It should arouse the attention of clinical. Clinical pharmacists should focus more on pathophysiological state, interaction, drug genome science to proceed, so we can summarize and analyze the occurrence regularity, and investigate its mechanism in order to protect the safety of patients with medication. It can help clinical pharmacists to take responsibility for the uprising.     

CYP450酶与中药代谢相互作用及酶活性测定的研究进展

药物对于人体属于外源性化合物,进入人体后将被许多酶所代谢。CYP450酶作为主要的代谢酶,且是重要的药物I相代谢酶,人体约75%的药物代谢是通过CYP450酶进行,而且CYP450酶是引起中药-中药(药对)、中药-西药等联合用药时药物相互作用产生的关键因素。为明确代谢酶与中药代谢的相互作用关系,普遍以酶活性作为评价指标,即以CYP450酶活性的增强和降低来推断中药有效成分及提取物等对酶的诱导或抑制作用。目前,代谢酶活性测定的常用方法是Cocktail探针药物法,其中探针底物的选择是关键。这对研究药物在机体内的吸收、分布、代谢及排泄(ADME)过程有着重大意义。该文就中药、中药有效成分、中药提取物及Cocktail探针底物等与CYP450酶的相互作用进行了综述,以期对将来的相关研究有借鉴和指导意义。     

多成分药物代谢理论及技术方法分析

多成分药物代谢是以多成分中各成分间的转运蛋白相互影响及药物代谢酶相互影响为核心,以多成分同时测定为原则,以多成分环境影响的代谢变化为重点研究方向,其理论内容由序贯代谢、并发代谢、多重代谢组成,在坚持多成分同时测定、代谢连续时间记录、代谢连续空间记录及定性与定量结合的研究原则下,综合运用体内实验、在体实验及离体实验方法开展研究。在直观比较分析与量化数据评价的模式下,可认为多成分药物代谢是学术基础扎实、技术手段先进的新兴科研方向。     

In vitro inhibition of metabolism but not transport of gliclazide and repaglinide by Cree medicinal plant extracts

Ethnopharmacological relevance

Interactions between conventional drug and traditional medicine therapies may potentially affect drug efficacy and increase the potential for adverse reactions. Cree traditional healing is holistic and patients may use medicinal plants simultaneously with the conventional drugs. However, there is limited information that these medicinal plants may interact with drugs and additional mechanistic information is required. In this study, extracts from traditionally used Cree botanicals were assessed for their potential interaction that could alter the disposition of two blood glucose lowering drugs, gliclazide (Diamicron) and repaglinide (Gluconorm) though inhibition of either metabolism or transport across cell membranes.

Materials and methods

The effect of 17 extracts on metabolism was examined in a human liver microsome assay by HPLC and individual cytochrome P450s 2C9, 2C19, 2C8 and 3A4 in a microplate fluorometric assay. Gliclazide, rhaponticin and its aglycone derivative, rhapontigenin were also examined in the fluorometric assay. The effect on transport was examined with 11 extracts using the intestinal epithelial Caco-2 differentiated cell monolayer model at times up to 180 min.

Results

Both blood glucose lowering medications, gliclazide and repaglinide traversed the Caco-2 monolayer in a time-dependent manner that was not affected by the Cree plant extracts. Incubation of the Cree plant extracts inhibited CYP2C9, 2C19, 2C8 and 3A4-mediated metabolism, and the formation of four repaglinide metabolites: M4, m/z 451-A, m/z 451-B and the glucuronide of repaglinide in the human liver microsome assay. Gliclazide caused no significant inhibition. Likewise, rhaponticin had little effect on the enzymes causing changes of less than 10% with an exception of 17% inhibition of CYP2C19. By contrast, the aglycone rhapontigenin showed the greatest effects on all CYP-mediated metabolism. Its inhibition ranged from a mean of 58% CYP3A4 inhibition to 89% inhibition of CYP2C9. While rhaponticin and the aglycone did not show significant effects on repaglinide metabolism, they demonstrated inhibition of gliclazide metabolism. The aglycone significantly affected levels of gliclazide and its metabolites.

Conclusion

These studies demonstrate that the Cree plant extracts examined have the potential in vitro to cause drug interactions through effects on key metabolic enzymes.     

应用Cocktail探针药物法分析中药对CYP450酶活性影响的研究进展

Cocktail探针药物法作为一种快速、准确、高通量的评价CYP450酶活性的研究方法广泛应用于药物研发早期筛选、药物代谢途径及机制研究、药物相互作用研究、指导临床合理用药、上市药物再评价及协助肝肾病理研究等诸多领域。该文对Cocktail探针药物法的特点做简要说明,着重介绍其在中医药领域内的应用进展,从中药活性成分的代谢机制研究,炮制过程,方剂配伍对CYP450的影响,揭示中成药CYP450代谢特点规律,民族药学应用情况,中药保肝作用及中医证候模型研究等,并总结归纳现有研究成果,比较其在中西医药领域内应用的异同点,为该领域的深入研究工作提供参考。