Drug Metabolism and Drug Interactions最新文献

英文中文

Need for pharmacogenomic information also for generic medications: recommendation of the European Society of Pharmacogenomics and Theranostics (ESPT). 仿制药也需要药物基因组学信息:欧洲药物基因组学和治疗学学会(ESPT)的建议。

Drug Metabolism and Drug Interactions

Pub Date : 2012-01-01 DOI: 10.1515/dmdi-2012-0010

Gérard Seist

As of 2007, PLAVIX (the original brand name of clopidogrel) had been the second top-selling drug in the world and is, presently, prescribed and marketed in nearly 110 countries. Clopidogrel is currently the thienopyridine of choice for dual antiplatelet therapy (in combination with aspirin) in patients with the full spectrum of acute coronary syndrome and in those undergoing percutaneous coronary intervention and stenting. In a plethora of pharmacogenomic studies on PLAVIX, it has been shown that clopidogrel is a prodrug that requires biotransformation to an active metabolite by CYP450 enzymes (mainly CYP2C19) and paraoxonase 1 (PON-1). There is signifi cant inter-individual variability in the response to PLAVIX, with up to 40 % of patients being classifi ed as non-responders, poor responders, or resistant to this drug. Pharmacogenomic information on PLAVIX reveals that genetic polymorphisms of CYP enzymes (most commonly CYP2C19*2), PON-1, and also the ABCB 1 transporter contribute to variation in the response of individual patients to the drug. In March 2010, the Food and Drug Administration (FDA) released a “ boxed warning ” on PLAVIX addressing the need for pharmacogenomic testing (for detecting CYP2C19 loss-of-function polymorphisms) to identify patients ’ altered PLAVIX metabolism, and thus their risk for a suboptimal clinical response to this drug. On the basis of an expanding database, and as an approach to the FDA boxed warning, the American College of Cardiology Foundation/ American Heart Association-convened writing committee developed an evidence-based guideline, “ Recommendations for Practice, ” in July 2010. These documents were validated in France in October 2010 and the SmPC (Summary of Product Characteristics) of PLAVIX was updated accordingly by the French regulatory agency (AFSSAPS).

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引用次数: 0

Cytochrome P450 2B6: function, genetics, and clinical relevance. 细胞色素P450 2B6:功能，遗传学和临床相关性。

Drug Metabolism and Drug Interactions

Pub Date : 2012-01-01 DOI: 10.1515/dmdi-2012-0027

Miia Turpeinen, Ulrich M Zanger

Cytochrome P450 (CYP) 2B6 belongs to the set of important hepatic drug-metabolizing CYPs. It makes up roughly 3%-6% of total hepatic CYP content and metabolizes several pharmaceuticals including bupropion, efavirenz, cyclophosphamide, pethidine, ketamine and propofol. The enzyme is susceptible to drug-drug interactions by enzyme induction and inhibition. In addition to drugs, CYP2B6 is able to both detoxify and bioactivate a number of procarcinogens and environmental agents including pesticides and herbicides. There is an extensive interindividual variability in the expression of CYP2B6, which is in part explained by extensive genetic polymorphism. CYP2B6 is one of the most polymorphic CYP genes in humans with over 100 described SNPs, numerous complex haplotypes and distinct ethnic and racial frequencies. This review summarizes the basic properties of CYP2B6 and the main characteristics of clinical relevance.

细胞色素P450 (CYP) 2B6是一类重要的肝脏药物代谢CYP。它约占肝脏CYP总含量的3%-6%，并代谢几种药物，包括安非他酮、依非韦伦、环磷酰胺、哌啶、氯胺酮和异丙酚。该酶易受药物-药物相互作用的酶诱导和抑制。除药物外，CYP2B6还能够解毒和生物激活许多致癌原和环境因子，包括杀虫剂和除草剂。CYP2B6的表达存在广泛的个体间差异，这在一定程度上可以通过广泛的遗传多态性来解释。CYP2B6是人类最具多态性的cypp基因之一，具有超过100个已描述的snp，众多复杂的单倍型和不同的民族和种族频率。本文就CYP2B6的基本特性及其临床意义进行综述。

引用次数: 88

High-performance liquid chromatography method using ultraviolet detection for the quantification of aripiprazole and dehydroaripiprazole in psychiatric patients. 采用紫外检测的高效液相色谱法定量测定精神病患者阿立哌唑和脱氢阿立哌唑的含量。

Drug Metabolism and Drug Interactions

Pub Date : 2012-01-01 DOI: 10.1515/dmdi-2012-0016

Pedro Dorado, Fernando de Andrés, María Eugenia G Naranjo, Eva M Peñas-Lledó, Idilio González, Antonio P González, Alfredo de la Rubia, Adrián Llerena

Background: Aripiprazole (ARI) is an antipsychotic drug that is metabolized to dehydroaripiprazole (DARI) by CYP2D6. Because of the large interindividual variability in ARI and DARI plasma concentrations, therapeutic drug monitoring may be of use in psychiatric patients during treatment with ARI. The aim of the present study was to develop a simple and reliable method for the quantitative determination of ARI and DARI in plasma using liquid-liquid extraction and reverse-phase high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. The method was tested in psychiatric patients during regular treatment with ARI.

Methods: Separation was by the liquid-liquid method, and UV detection at 254 nm. Linear responses for ARI and DARI were obtained between 2 and 1000 ng/mL, and precision assays were lower than 10.4 for both analytes.

Results: Lower limit of quantification and detection were 1 and 0.38 ng/mL for ARI and 0.78 and 0.44 ng/mL for DARI, respectively. The method was successfully applied to plasma samples drawn from 22 patients with concentrations ranging between 2 and 189 ng/mL for ARI and between 11 and 359 ng/mL for DARI.

Conclusions: The chromatographic method developed has been demonstrated to be sensitive and reliable for the measurement of ARI and DARI simultaneously in human plasma, and the present method represents an alternative procedure to evaluate plasma concentration in patients during treatment with ARI.

背景:阿立哌唑(ARI)是一种通过CYP2D6代谢为脱氢阿立哌唑(DARI)的抗精神病药物。由于ARI和DARI血浆浓度的个体间差异很大，治疗药物监测可能在ARI治疗期间用于精神患者。本研究的目的是建立一种简便、可靠的液液萃取-紫外反相高效液相色谱法(HPLC)定量测定血浆中ARI和DARI的方法。该方法在ARI常规治疗期间的精神病患者中进行了测试。方法:采用液液法分离，在254 nm处进行紫外检测。ARI和DARI的线性响应在2 ~ 1000 ng/mL之间，两种分析物的精密度均低于10.4。结果:ARI的定量下限和检测下限分别为1和0.38 ng/mL, DARI的定量下限和检测下限分别为0.78和0.44 ng/mL。该方法成功地应用于22例急性呼吸道感染患者的血浆样品，浓度范围为2至189 ng/mL, DARI浓度范围为11至359 ng/mL。结论:所开发的色谱方法已被证明对同时测量人血浆中ARI和DARI敏感可靠，本方法是评估ARI治疗期间患者血浆浓度的另一种方法。

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引用次数: 4

Development of a HPLC method for the determination of losartan urinary metabolic ratio to be used for the determination of CYP2C9 hydroxylation phenotypes. 建立氯沙坦尿代谢比的高效液相色谱测定方法，用于CYP2C9羟基化表型的测定。

Drug Metabolism and Drug Interactions

Pub Date : 2012-01-01 DOI: 10.1515/dmdi-2012-0018

Pedro Dorado, Esther Machín, Fernando de Andrés, María-Eugenia Naranjo, Eva M Peñas-Lledó, Adrián Llerena

Background: Losartan is metabolized to losartan carboxylic acid (E-3174) by the polymorphic cytochrome CYP2C9. The aim of the study was to develop a high-performance liquid chromatographic (HPLC) method with fluorescence detection for simultaneously measuring losartan and its metabolite E-3174 in urine to evaluate the losartan urinary metabolic ratio (MR: losartan/E-3174) for CYP2C9 phenotyping in humans.

Methods: The compounds were separated in a reversed-phase chromatographic column and detected by fluorescence at a wavelength of 250 nm for excitation and of 370 nm for emission.

Results: No analytical interferences with endogenous compounds were found, and the extraction recoveries were over 88%. Limits of quantification of 2 ng mL-1 for losartan and 5 ng mL-1 for E-3174 were achieved, as well as good reproducibility with coefficients of variation of <9% in all cases. Analyses with the present HPLC method show significant differences (p<0.05) in losartan MRs between the four CYP2C9 genotype groups in 13 Spanish healthy volunteers.

Conclusions: The method developed is simple and affordable, as well as sensitive and reliable to calculate the MR. Therefore, it appears to be useful for CYP2C9 phenotyping using losartan as a drug test in populations, such as Hispanics with different allele combinations.

背景:氯沙坦被多态细胞色素CYP2C9代谢为氯沙坦羧酸(E-3174)。本研究的目的是建立高效液相色谱(HPLC)荧光检测同时测定尿中氯沙坦及其代谢物E-3174的方法，评估氯沙坦尿代谢比(MR: losartan/E-3174)对人CYP2C9表型的影响。方法:采用反相色谱柱分离，荧光检测，激发波长为250 nm，发射波长为370 nm。结果:内源化合物对分析无干扰，提取回收率在88%以上。氯沙坦和E-3174分别获得了2 ng mL-1和5 ng mL-1的定量限，且变异系数重复性好。结论:所建立的方法简便、经济、mr计算灵敏、可靠，可用于不同等位基因组合人群(如西班牙裔)中氯沙坦作为药物试验的CYP2C9表型分析。

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引用次数: 8

Public Health Genomics and personalized healthcare: a pipeline from cell to society. 公共健康基因组学和个性化医疗保健:从细胞到社会的管道。

Drug Metabolism and Drug Interactions

Pub Date : 2012-01-01 DOI: 10.1515/dmdi-2012-0028

Angela Brand

Truly personalized healthcare facilitating the management of personal health drives a fundamental change not just in what is known but also in how we think of ourselves and the way we are living, thus redefining our society (1) . We have to prepare now – just in time! – for all the various organizational changes ahead of us. The political will is there. However, the real paradigm shift depends on the willingness to restructure our current policies, to support knowledge transfer to maximize benefit to public health, and – most important – to change our minds. So far, all stakeholders including policy-makers and the private sector are struggling to translate the emerging knowledge into public health. Public Health Genomics (PHG) is the area of public health ensuring that scientific advances in genomics ( “ from cell ... ” ) triggered by innovative technologies are timely, effectively and responsibly translated into health policies and practice for the benefit of population health ( “ ... to society ” ). But, what evidence emerging from basic sciences needs to be translated ? New insights are being obtained from genomics, proteomics, transcriptomics, metabolomics, epigenomics, microbiomics, and other “ omics ” technologies. As these data are integrated through the use of information and communication technologies (ICT), we are at the edge of achieving an understanding of the systems biology and systems biomedicine of human health and disease that also incorporates environmental contributions such as lifestyle, toxic agents, social and economic factors, as well as health systems determinants. In this way, we can begin to envisage new approaches to the promotion and management of human health across the entire life course of an individual. Indeed, we can now consider a future involving truly personalized healthcare in which technological advances are placed at the service of population health. The evidence we now require to demonstrate the benefit of new technologies will need to follow a new paradigm, however. What is required is an assessment of individual benefit rather than overall effects in large populations or even subpopulations of patients. Thus, public health assessment and evaluation tools must now address concepts such as “ personal utility ” rather than clinical utility. These developments and the involvement of the patient brought forward the concept of P4 (predictive, preventive, personalized and participatory) medicine serving already as a blueprint for Public Health Genomics to prepare healthcare systems and policy-makers for this shift in our approach to healthcare. The P4 medicine is no longer a vision, it is a mission! We can and should go beyond the P4 medicine and recognize in the light of a “ systems approach to public health ” , that (2) : – Common complex diseases can be considered in terms of a constellation of “ rare ” diseases, each of which reflects a complex biological system. – We are moving away from a traditional class

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引用次数: 18

European Best Practice Guidelines for Quality Assurance, Provision and Use of Genome-based Information and Technologies: the 2012 Declaration of Rome. 欧洲基因组信息和技术质量保证、提供和使用最佳实践指南:2012年罗马宣言。

Drug Metabolism and Drug Interactions

Pub Date : 2012-01-01 DOI: 10.1515/dmdi-2012-0026

Angela Brand, Jonathan A Lal

*Corresponding author: Prof. Angela Brand, MD, PhD, MPH, Coordinator PHGEN, Institute for Public Health Genomics, Cluster of Genetics and Cell Biology, Faculty of Health, Medicine and Life Science, Maastricht University, Universiteitssingel 40, 6229 ER Maastricht, The Netherlands, Phone: + 31-646705062, E-mail: a.brand@maastrichtuniversity.nl Angela Brand: Institute for Public Health Genomics , Research Schools GROW and CAPHRI, Maastricht University, Maastricht , The Netherlands Jonathan A. Lal : Institute for Public Health Genomics , Research Schools GROW and CAPHRI, Maastricht University, Maastricht , The Netherlands

引用次数: 26

Report from the European Society of Pharmacogenomics and Theranostics (ESPT) Inaugural Symposium 2011 in Bled. 2011年欧洲药物基因组学和治疗学学会(ESPT)在布莱德举行的首届研讨会报告。

Drug Metabolism and Drug Interactions

Pub Date : 2012-01-01 DOI: 10.1515/dmdi-2012-0004

Irena Prodan Žitnik, Janja Marc

No abstract available.

引用次数: 0

Analysis of the molecular interactions and complexation of chloroquine with bovine serum albumin. 氯喹与牛血清白蛋白的分子相互作用及络合作用分析。

Drug Metabolism and Drug Interactions

Pub Date : 2011-11-05 DOI: 10.1515/DMDI.2011.030

Mahmoud Kandeel, Yukio Kitade

Background: Pharmacokinetic parameters, drug bioavailability, and biological activities depend on the mechanisms of interaction with serum albumin. In this study, the binding properties as well as mechanisms of interaction of chloroquine with bovine serum albumin (BSA) were investigated.

Methods: The binding of chloroquine with BSA was carried out using a microcalorimetric approach. The mechanism of binding, the number of binding molecules as well as changes of BSA upon complexation with chloroquine were investigated.

Results: The binding isotherms indicated a variable number of binding sites of chloroquine on one molecule of BSA. At lower temperatures, larger numbers of binding sites were available for chloroquine, these decrease by increasing the temperature. The binding constant of chloroquine with BSA varied from 9.4×10³ M⁻¹ at 25°C to 5.7×10³ M⁻¹ at 40°C. Chloroquine showed temperature-dependent binding affinity, with stronger affinity at lower temperature. By increasing the temperature, from 25°C to 40°C, the binding affinity was decreased by approximately 60% of its value.

Conclusions: Chloroquine showed weak binding affinity with BSA. The weak binding affinity of chloroquine with BSA is important in determining the drug-drug interactions at the binding sites of BSA. The presence of stronger binding ligands, e.g., chloramphenicol, tetracyclines or diclofenac, can compete with chloroquine for its binding sites, and therefore lowers its serum albumin binding. This study will be helpful in understanding the binding properties of mechanisms of interaction of chloroquine with BSA.

背景:药代动力学参数、药物生物利用度和生物活性取决于与血清白蛋白相互作用的机制。本文研究了氯喹与牛血清白蛋白(BSA)的结合特性及其相互作用机制。方法:采用微量热法测定氯喹与牛血清白蛋白的结合。研究了BSA与氯喹的结合机理、结合分子数以及与氯喹络合后BSA的变化。结果:结合等温线显示氯喹在一个牛血清白蛋白分子上的结合位点数目是可变的。在较低的温度下，氯喹有大量的结合位点，这些位点随着温度的升高而减少。氯喹与BSA的结合常数在25°C时为9.4×10³M⁻¹，在40°C时为5.7×10³M⁻¹。氯喹具有温度依赖性的结合亲和力，在较低的温度下亲和力更强。随着温度的升高，从25°C到40°C，结合亲和力降低了约60%。结论:氯喹与牛血清白蛋白的结合亲和力较弱。氯喹与牛血清白蛋白的弱结合亲和力对确定牛血清白蛋白结合位点的药物-药物相互作用具有重要意义。较强结合配体的存在，如氯霉素、四环素或双氯芬酸，可与氯喹竞争其结合位点，从而降低其血清白蛋白结合。本研究将有助于了解氯喹与牛血清白蛋白相互作用的结合特性和机制。

{"title":"Analysis of the molecular interactions and complexation of chloroquine with bovine serum albumin.","authors":"Mahmoud Kandeel, Yukio Kitade","doi":"10.1515/DMDI.2011.030","DOIUrl":"https://doi.org/10.1515/DMDI.2011.030","url":null,"abstract":"Background: Pharmacokinetic parameters, drug bioavailability, and biological activities depend on the mechanisms of interaction with serum albumin. In this study, the binding properties as well as mechanisms of interaction of chloroquine with bovine serum albumin (BSA) were investigated.Methods: The binding of chloroquine with BSA was carried out using a microcalorimetric approach. The mechanism of binding, the number of binding molecules as well as changes of BSA upon complexation with chloroquine were investigated.Results: The binding isotherms indicated a variable number of binding sites of chloroquine on one molecule of BSA. At lower temperatures, larger numbers of binding sites were available for chloroquine, these decrease by increasing the temperature. The binding constant of chloroquine with BSA varied from 9.4×10³ M⁻¹ at 25°C to 5.7×10³ M⁻¹ at 40°C. Chloroquine showed temperature-dependent binding affinity, with stronger affinity at lower temperature. By increasing the temperature, from 25°C to 40°C, the binding affinity was decreased by approximately 60% of its value.Conclusions: Chloroquine showed weak binding affinity with BSA. The weak binding affinity of chloroquine with BSA is important in determining the drug-drug interactions at the binding sites of BSA. The presence of stronger binding ligands, e.g., chloramphenicol, tetracyclines or diclofenac, can compete with chloroquine for its binding sites, and therefore lowers its serum albumin binding. This study will be helpful in understanding the binding properties of mechanisms of interaction of chloroquine with BSA.","PeriodicalId":11319,"journal":{"name":"Drug Metabolism and Drug Interactions","volume":"27 1","pages":"41-6"},"PeriodicalIF":0.0,"publicationDate":"2011-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2011.030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40128921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Interaction of human multidrug and toxin extrusion 1 (MATE1) transporter with antineoplastic agents. 人多药和毒素挤出1 (MATE1)转运体与抗肿瘤药物的相互作用。

Drug Metabolism and Drug Interactions

Pub Date : 2011-01-01 Epub Date: 2011-11-07 DOI: 10.1515/DMDI.2011.024

Julia Grottker, Albert Rosenberger, Gerhard Burckhardt, Yohannes Hagos

Background: The transport of endogenous and exogenous organic cations across the plasma membrane of cells is mediated by multispecific organic cation transporters (OCTs), and the multidrug and toxin extrusion (MATE) transporters. MATE belongs to the SLC47 transporter family consisting of only two members, MATE1 and MATE2-K. MATE2-K is exclusively expressed in the kidney at the apical membrane of proximal tubular epithelial cells. MATE1 is highly expressed in the kidney, liver, skeletal muscle and also in adrenal glands, testes and heart. MATE1 exchanges organic cations against protons both in influx as well as in efflux modes.

Methods: Here, we examined the interaction of 25 antineoplastic agents with human MATE1. We generated stably transfected MATE1-HEK293 cells and determined the inhibition of MATE1-mediated [(3)H]1-methyl-4-phenylpyridinium (MPP) uptake by the antineoplastic agents.

Results: We found a significant inhibition of MATE1-mediated MPP uptake by several antineoplastic agents and pH dependent IC(50)values for mitoxantrone (7.8 μM at pH 7.4 and 0.6 μM at pH 8.5) as well as for irinotecan (4.4 μM at pH 7.4 and 1.1 μM at pH 8.5), respectively.

Conclusions: We suggest that hMATE1 could play a role in chemosensitivity of tumor cells. In addition, hepatic and renal MATE1 could potentially be involved in drug-drug-interactions as well as in drug metabolism and excretion during chemotherapy.

背景:内源性和外源性有机阳离子在细胞膜上的转运是由多特异性有机阳离子转运体(OCTs)和多药物和毒素挤出转运体(MATE)介导的。MATE属于SLC47转运蛋白家族，由MATE1和MATE2-K两个成员组成。MATE2-K仅在肾近端小管上皮细胞的顶膜表达。MATE1在肾脏、肝脏、骨骼肌以及肾上腺、睾丸和心脏中高度表达。MATE1在内流和外排模式下与质子交换有机阳离子。方法:研究了25种抗肿瘤药物与人MATE1的相互作用。我们生成了稳定转染的MATE1-HEK293细胞，并测定了抗肿瘤药物对mate1介导的[(3)H]1-甲基-4-苯基吡啶(MPP)摄取的抑制作用。结果:我们发现几种抗肿瘤药物对mate1介导的MPP摄取有显著的抑制作用，并且pH依赖性IC(50)值分别为米托蒽醌(7.8 μM, pH 7.4和0.6 μM, pH 8.5)和伊立替康(4.4 μM, pH 7.4和1.1 μM, pH 8.5)。结论:hMATE1可能在肿瘤细胞的化疗敏感性中发挥作用。此外，肝脏和肾脏MATE1可能参与药物-药物相互作用以及化疗期间的药物代谢和排泄。

{"title":"Interaction of human multidrug and toxin extrusion 1 (MATE1) transporter with antineoplastic agents.","authors":"Julia Grottker, Albert Rosenberger, Gerhard Burckhardt, Yohannes Hagos","doi":"10.1515/DMDI.2011.024","DOIUrl":"https://doi.org/10.1515/DMDI.2011.024","url":null,"abstract":"Background: The transport of endogenous and exogenous organic cations across the plasma membrane of cells is mediated by multispecific organic cation transporters (OCTs), and the multidrug and toxin extrusion (MATE) transporters. MATE belongs to the SLC47 transporter family consisting of only two members, MATE1 and MATE2-K. MATE2-K is exclusively expressed in the kidney at the apical membrane of proximal tubular epithelial cells. MATE1 is highly expressed in the kidney, liver, skeletal muscle and also in adrenal glands, testes and heart. MATE1 exchanges organic cations against protons both in influx as well as in efflux modes.Methods: Here, we examined the interaction of 25 antineoplastic agents with human MATE1. We generated stably transfected MATE1-HEK293 cells and determined the inhibition of MATE1-mediated [(3)H]1-methyl-4-phenylpyridinium (MPP) uptake by the antineoplastic agents.Results: We found a significant inhibition of MATE1-mediated MPP uptake by several antineoplastic agents and pH dependent IC(50)values for mitoxantrone (7.8 μM at pH 7.4 and 0.6 μM at pH 8.5) as well as for irinotecan (4.4 μM at pH 7.4 and 1.1 μM at pH 8.5), respectively.Conclusions: We suggest that hMATE1 could play a role in chemosensitivity of tumor cells. In addition, hepatic and renal MATE1 could potentially be involved in drug-drug-interactions as well as in drug metabolism and excretion during chemotherapy.","PeriodicalId":11319,"journal":{"name":"Drug Metabolism and Drug Interactions","volume":"26 4","pages":"181-9"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2011.024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30308373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

From systems biology and functional genomics to personalized health. 5th Biologie Prospective Santorini Conference, Island of Santorini, Greece, September 30-October 2, 2010. 从系统生物学和功能基因组学到个性化健康。第五届圣托里尼生物学展望会议，希腊圣托里尼岛，2010年9月30日至10月2日。

Drug Metabolism and Drug Interactions

Pub Date : 2011-01-01 Epub Date: 2011-03-16 DOI: 10.1515/DMDI.2011.104

引用次数: 0

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