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部分抗肿瘤药物基因组学研究进展 总被引:2,自引:2,他引:2
近年来,由于个体差异引起抗肿瘤药物疗效和毒副作用的不同受到越来越多的重视。药物基因组学的研究结果表明基因多态性与抗肿瘤药物个体间作用多样性及毒副作用之间的关系密切。本文就部分抗肿瘤药物基因组学的研究进展加以综述。 相似文献
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目的:介绍药物基因组学目前在国外临床应用的进展和实例.促进其在我国临床实践中的应用.提高个体化医疗的水平。方法:本文根据美国FDA批准的60多个包含药物基因组学信息的药品说明书,结合我们临床用药实际和目前可及的基因检测手段.对药物基因组学在个体化医疗中的实际应用情况进行总结,供临床药师和医师在治疗中尝试、应用或参考。结果与结论:基于基因多态性检测技术的药物基因组学已经广泛应用于临床,在提高药物疗效.降低药物毒副作用,调整药物剂量方面发挥了重要的作用,开辟了个体化医疗的新局面。 相似文献
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药物基因组学是研究影响药物吸收、转运,代谢,消除,作用等个体差异的基因特性即决定药物行为和敏感性的全部基因谱的新学科。本文综述药物基因组学在药物转运蛋白,药物代谢酶、药物作用靶点(如受体)的基因多态性方面的研究进展,以及药物基因组学指导临床合理用药中的策略。 相似文献
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药物基因组学及生物芯片应用 总被引:1,自引:0,他引:1
药物基因组学主要阐明药物代谢、药物转运和药物靶分子的基因多态性与药物作用、包括疗效和毒副作用之间的关系。目前药物基因组学通常是指以快速增长的人类基因组中所有基因信息,指导新药开发的一个领域。药物基因组学有可能从根本上改变药物临床治疗模式和新药开发方式。生物芯片技术在药物基因组学研究中的应用,必将有助于设计针对靶点的更为有效的新型药物,提高临床疾病的诊断和治疗水平。 相似文献
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随着药物基因组学、药物遗传学的发展,基因指导下个体化治疗成为提高化疗疗效的有效途径之一。确定药物的相关预测性分子标志物有助于指导临床治疗,提高疗效。吉西他滨(gemcitabine)作为多种肿瘤的有效化疗药物,其疗效与不良反应的差异与相关基因多态性的关系日益受到人们的关注。本文就吉西他滨各相关酶的基因多态性情况及其对疗效的影响进行综述。 相似文献
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药物基因组学及其应用 总被引:6,自引:0,他引:6
药物基因组学基于基因多态性基础上,研究影响药物吸收、转运、代谢、消除等个体差异的基因特性。本文综述了药物基因组学的发展历程和概念内涵,以及在个体化医疗、合理用药、新药开发等方面的应用情况。 相似文献
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《中国药房》2017,(35):5028-5032
目的:了解瑞格列奈药物基因组学的研究进展,为瑞格列奈的临床个体化给药提供参考。方法:查阅近年来国内外相关文献,就瑞格列奈的药物基因组学的研究进行归纳和总结。结果:瑞格列奈相关的药物基因组学研究主要集中于药物代谢和转运相关基因、药物作用靶点和受体的编码基因、2型糖尿病(T2DM)易感基因等方面,其中KCNQ1、Neuro D1/BETA2、PAX4、NOS1AP、SLC30A8、IGF2BP2、UCP2、NAMPT为代表的T2DM易感基因对瑞格列奈药效学的影响是目前研究的重点。T2DM易感基因可能通过影响胰岛B细胞的增殖、腺苷三磷酸敏感性钾通道(KATP)和电压门控Ca~(2+)通道的表达和活性以及胰岛素分泌,从而增加T2DM的易感性并影响药物治疗反应性。CYP2C8、CYP3A4、SLCO1B1和MDR1等与药物代谢和转运有关的基因多态性可能影响瑞格列奈的药-时曲线下面积、峰浓度、半衰期和清除率等,间接影响药物疗效和安全性。在开展药物基因组学研究时,还应根据不同种族的等位基因频率来选择基因多态性位点,以期获得更大的临床应用价值。结论:基因多态性是瑞格列奈治疗反应性个体差异的部分原因,有望通过基因导向的个体化治疗提高疗效、减少不良反应。 相似文献
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药物基因组学涉及所有编码与药物代谢、处置、转运蛋白、靶蛋白等相关的基因。从基因水平研究基因多态性与药物疗效关系以及预测不良反应发生将成为消化系统疾病临床治疗新的切入点。药物基因组学将成为传统方法选药及给药方案制定的重要补充。 相似文献
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Pharmacogenomics in drug-metabolizing enzymes catalyzing anticancer drugs for personalized cancer chemotherapy 总被引:3,自引:0,他引:3
Cancer chemotherapy is characterized by a broad range of efficacy and toxicity among patients. Most anticancer drugs show wide interindividual variability in pharmacokinetics and have narrow therapeutic windows. Since drug metabolism is often an essential determinant of interindividual variability in pharmacokinetics, pharmacogenomic studies of drug-metabolizing enzymes are expected to rationalize cancer chemotherapy in terms of patient, treatment, and dosage selection. Candidate gene approaches to pharmacogenomics are based on existing knowledge in clinical pharmacology, used to select the target(s) to be analyzed. So far, the candidate gene approach has provided important clues for pharmacogenomic-based personalized chemotherapy with 6-mercaptopurine (6-MP), solely metabolized by thiopurine S-methyltransferase (TPMT), and irinotecan, mainly detoxified by UDP-glucuronosyltransferase 1A1 (UGT1A1). Reduced activity of TPMT caused by polymorphisms in the TPMT gene and decreased activity of UGT1A1 caused by UGT1A1*28 are related to severe toxic effects of 6-MP and irinotecan, respectively. In response to these findings, the Food and Drug Administration in the United States has supported clinical pharmacogenetic testing by revising the package inserts for these anticancer drugs. The genome wide approach to pharmacogenomics has gradually evolved with continued progress in genome sciences and technologies. This approach can disclose previously unknown relations of factors, as well as identify potential multigenetic associations. The genome wide approach can also identify genes underlying the phenotypic effects of anticancer drugs. This approach may play a complemental role to the candidate gene approach in the future of cancer pharmacogenomics. This review describes recent progress in pharmacogenomics in the field of cancer chemotherapy. 相似文献
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Single nucleotide polymorphisms (SNPs) can be used in clinical association studies to determine the contribution of genes to drug efficacy. However, it would be extremely inefficient to test all the 10 million common SNPs for an association study. Here we review haplotype analysis and pattern-recognition techniques to systematically select candidate SNPs for candidate-gene association studies in pharmacogenomics. First, we survey linkage disequilibrium methods to identify tag SNPs and explore the use of haplotypes as genetic markers that are correlated and associated with drug efficacy. Secondly, we investigate pattern-recognition algorithms and statistical analyses to assess drug efficacy based on SNPs and other factors. Finally, we study pattern-recognition approaches to evaluate the epistasis among genes and SNPs. These techniques may provide tools for clinical association studies and help find genes/SNPs involved in responses to therapeutic drugs or adverse drug reactions. 相似文献
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Unpredictable efficacy and toxicity are major hurdles in the administration of many medications. By identifying inherited DNA polymorphisms that influence drug disposition and effects, pharmacogenomics is an exciting tool for the individualization of drug therapies. Single nucleotide polymorphisms (SNP) in genes encoding drug metabolizing enzymes, drug transporters, and DNA repair genes have recently been shown to influence drug toxicity and efficacy. This review will discuss clinically relevant examples of genetic polymorphisms that influence the outcome of drug therapy, and possibilities for future applications of pharmacogenomics. 相似文献
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Adverse drug reactions: role of pharmacogenomics. 总被引:2,自引:0,他引:2
Adverse drug reactions (ADRs) are a significant cause of morbidity and mortality. The majority of ADRs can be considered common disorders with considerable clinical variability (clinical phenotype) in which many different genes are involved together with environmental variables. Pharmacogenomics is the study of how genes affect the individual response to drugs. There is some evidence that in the future the use of pharmacogenomics could help to reduce ADRs, as it aims to predict which patients are likely to respond to a particular drug and which patients are likely to have significant ADRs. In this article some examples of genetic polymorphisms affecting drug kinetics, drug toxicity and hypersensitivity related to ADRs are illustrated. 相似文献
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药物基因组学与合理用药研究进展 总被引:3,自引:0,他引:3
目的介绍药物基因组学及其在临床制定治疗方案中的应用。方法根据有关文献 ,综合分析、归纳总结药物基因组学和临床药物基因组学的发展、研究内容及与个体化用药的关系。结果药物基因组学研究表明 ,基因多态性与药物作用多样性之间的关系非常密切。结论药物基因组学为安全、有效和合理用药提供了理论依据。 相似文献
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Wu AH 《Pharmacogenomics》2007,8(7):851-861
Despite the fact that warfarin has been used as an anticoagulant for many years, the safety profile for this drug has been poor. Inappropriate dosing continues to contribute to significant morbidity and mortality due to thrombotic disease and bleeding. Therefore, there is a need for the development, characterization and implementation of dosing algorithms using a patient's demographic information and genotype. Recently, polymorphisms in two genes, cytochrome P450 2C9 and vitamin K epoxide reductase complex 1, have been shown to affect warfarin's pharmacogenomics and pharmacodynamics, respectively. Adding genotypes to a dosing algorithm may enable better prediction of initial warfarin dosing than use of demographic data alone. An advisory committee of the US FDA voted on November 14, 2005, to require manufacturers of warfarin to relabel their product, indicating that genotyping is recommended prior to drug administration. The exact date when this recommendation will be enacted remains to be determined. Successful implementation of pharmacogenomics into clinical practice requires genotyping results that can be translated directly into clinical decisions. The development of a warfarin dosing algorithm that includes genotyping may be the means to achieve this goal. 相似文献
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Pharmacogenomics of psychiatric disorders 总被引:3,自引:0,他引:3
Pharmacogenomics, the utilization of genetic information to predict outcome of drug treatment (therapeutic and side-effects), holds great promise for clinical medicine. The pharmacotherapy of psychiatric disorders exhibits wide variability in therapeutic response with little scientific guidance for treatment on a patient-by-patient basis. The emerging field of pharmacogenomics holds great potential for refining and optimizing psychopharmacology. Key components for future development of the pharmacogenomics of psychiatric disorders include understanding the mechanism of drug action, identification of candidate genes and their variants, and well-conducted clinical trials. In this article, data from recent studies are examined with particular emphasis on methodological requirements and direction for future research. 相似文献