Drug Metabolism and Drug Interactions最新文献_第2页

In vitro inhibitory effects of herbal supplements on tamoxifen and irinotecan metabolism. 草药补充剂对他莫昔芬和伊立替康代谢的体外抑制作用。

Drug Metabolism and Drug Interactions Pub Date : 2014-01-01 DOI: 10.1515/dmdi-2014-0017

Fran Grappe, Gwen Nance, Lori Coward, Greg Gorman

{"title":"In vitro inhibitory effects of herbal supplements on tamoxifen and irinotecan metabolism.","authors":"Fran Grappe, Gwen Nance, Lori Coward, Greg Gorman","doi":"10.1515/dmdi-2014-0017","DOIUrl":"https://doi.org/10.1515/dmdi-2014-0017","url":null,"abstract":"Background: As the use of herbal supplements continues to rise throughout the world, the potential for drug-herbal interactions also increases. For chemotherapeutic prodrugs, this interaction could prevent the metabolic conversion of the prodrug to its active metabolite(s), thereby potentially resulting in subtherapeutic systemic exposure of the drug and reduced efficacy of the therapy.Methods: In this study, in vitro metabolism with human liver microsomes is used to measure the impact of ten commonly used herbal supplements on the biotransformation of the chemotherapeutic prodrugs tamoxifen (TAM) and irinotecan (IR).Results: Four of the herbals tested, echinacea, ginseng, lemon balm, and skullcap, were found to be strong inhibitors of the CYP450 enzymatic bioactivation pathways of TAM with IC50 values as percent of a single dose ranging from 0.019% to 0.34%. Two of the herbals, skullcap and lemon balm, were found to inhibit the carboxyesterase pathway of IR with values of 0.21 and 0.25, respectively.Conclusions: Our data suggests that based on the measured IC50 values that skullcap and lemon balm could have potential negative clinical impact on the bioactivation of TAM but not likely with IR.","PeriodicalId":11319,"journal":{"name":"Drug Metabolism and Drug Interactions","volume":"29 4","pages":"269-79"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/dmdi-2014-0017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32610228","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: 3

The pharmacogenetics of drug metabolizing enzymes in the Lebanese population. 黎巴嫩人群中药物代谢酶的药物遗传学。

Drug Metabolism and Drug Interactions Pub Date : 2014-01-01 DOI: 10.1515/dmdi-2013-0058

Safaa Ossaily, Nathalie K Zgheib

引用次数: 10

Molecular functionality of CYP2C9 polymorphisms and their influence on drug therapy. CYP2C9多态性的分子功能及其对药物治疗的影响。

Drug Metabolism and Drug Interactions Pub Date : 2014-01-01 DOI: 10.1515/dmdi-2014-0001

Yazun Bashir Jarrar, Su-Jun Lee

{"title":"Molecular functionality of CYP2C9 polymorphisms and their influence on drug therapy.","authors":"Yazun Bashir Jarrar, Su-Jun Lee","doi":"10.1515/dmdi-2014-0001","DOIUrl":"https://doi.org/10.1515/dmdi-2014-0001","url":null,"abstract":"CYP2C9 metabolizes approximately 20% of clinically used drugs, including the narrow therapeutic window drugs warfarin and phenytoin. More than 16,000 variants have been reported in the National Center for Biotechnology Information CYP2C9 database, as well as 58 alleles in the official P450 Nomenclature Committee website. Two single nucleotide polymorphisms represented by the CYP2C9*2 and CYP2C9*3 alleles have been studied extensively. However, in addition to these two alleles, other genetic factors and an individual's biological characteristics contribute to the overall drug phenotype. A major bottleneck for CYP2C9 pharmacogenomics in clinical field applications is the lack of knowledge regarding the numerous genetic polymorphisms and their molecular functionalities. An unmet gap exists between the ever-growing number of genetic variants and their molecular mechanisms. In the present review, functional changes of all known CYP2C9 protein coding alleles were predicted using in silico analyses and compared with the in vitro and in vivo data. We also summarize functional information from recently reported CYP2C9 variants. Regarding the previously known CYP2C9 variants, we provide an update on the functional information obtained from in vitro and in vitro data.","PeriodicalId":11319,"journal":{"name":"Drug Metabolism and Drug Interactions","volume":"29 4","pages":"211-20"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/dmdi-2014-0001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32339303","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: 25

Liver enzyme abnormalities during antipsychotic treatment: a case report of risperidone-associated hepatotoxicity. 抗精神病药物治疗期间肝酶异常:利培酮相关肝毒性1例报告。

Drug Metabolism and Drug Interactions Pub Date : 2014-01-01 DOI: 10.1515/dmdi-2013-0064

Enrique López-Torres, Agnes Süveges, Eva M Peñas-LLedó, Alvaro Doña, Pedro Dorado, Adrián LLerena, Roland Berecz

{"title":"Liver enzyme abnormalities during antipsychotic treatment: a case report of risperidone-associated hepatotoxicity.","authors":"Enrique López-Torres, Agnes Süveges, Eva M Peñas-LLedó, Alvaro Doña, Pedro Dorado, Adrián LLerena, Roland Berecz","doi":"10.1515/dmdi-2013-0064","DOIUrl":"https://doi.org/10.1515/dmdi-2013-0064","url":null,"abstract":"Background: Drug-induced liver enzyme abnormalities may indicate hepatic injury. Antipsychotic drugs also may cause increase in the liver enzymes and serum bilirubin levels. The present report evaluates the case of a patient with risperidone-associated hepatocellular damage.Case summary: A 19-year-old Caucasian man was admitted to the Department of Psychiatry with paranoid schizophrenia and risperidone was administered in a gradually increasing dose up to 8 mg/day. After 3 weeks of treatment, he experienced asthenia and weight loss. The level of aspartate aminotransferase was 283 IU/L (normal: <30 IU/L), and the alanine aminotransferase level was 778 IU/L (normal: <36 IU/L). Treatment with risperidone was immediately discontinued. Six days after drug withdrawal, the alanine aminotransferase level fell more than 50%, and a complete return to normalcy was seen within 2 months.Results: In the present case, a possible causal association between risperidone and hepatocellular damage has been observed due to the temporal relationship between the administration of the drug and the onset of hepatic abnormalities, and a following rapid recovery after stopping the drug. As the hepatic damage could be related to the plasma concentration of risperidone which is highly influenced by the hepatic enzyme CYP2D6, the patient was genotyped for CYP2D6. He was classified as homozygous wild type for CYP2D6.Conclusions: The risk for developing hepatotoxicity during risperidone therapy cannot be supported by the patient CYP2D6 genotype. In clinical practice, it may be recommended to obtain baseline liver function tests before starting risperidone and regular screening for liver enzyme changes during therapy.","PeriodicalId":11319,"journal":{"name":"Drug Metabolism and Drug Interactions","volume":" ","pages":"123-6"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/dmdi-2013-0064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40285291","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: 12

Pharmacogenetic potential biomarkers for carbamazepine adverse drug reactions and clinical response. 卡马西平不良反应和临床反应的药物遗传学潜在生物标志物。

Drug Metabolism and Drug Interactions Pub Date : 2014-01-01 DOI: 10.1515/dmdi-2013-0046

Nancy Monroy Jaramillo, Ingrid Fricke Galindo, Alberto Ortega Vázquez, Helgi Jung Cook, Adrián LLerena, Marisol López López

{"title":"Pharmacogenetic potential biomarkers for carbamazepine adverse drug reactions and clinical response.","authors":"Nancy Monroy Jaramillo, Ingrid Fricke Galindo, Alberto Ortega Vázquez, Helgi Jung Cook, Adrián LLerena, Marisol López López","doi":"10.1515/dmdi-2013-0046","DOIUrl":"https://doi.org/10.1515/dmdi-2013-0046","url":null,"abstract":"Carbamazepine (CBZ) is a first-line widely used anticonvulsant. It has a narrow therapeutic index and exhibits considerable interindividual and interethnic variability in clinical efficacy and adverse drug reactions including potentially life-threatening hypersensitivity reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis. The most important pharmacogenetic finding is related to the association of CBZ-induced hypersensitivity with human leukocyte antigens (HLA class I and II alleles). Moreover, genotyping for HLA-B*15:02 allele is required prior to initiating CBZ in Asians and Asian ancestry patients, demonstrating the usefulness of biomarkers to avoid adverse drug reactions. On the other hand, in order to explain the differences in the clinical response to CBZ, genetic polymorphisms in phase I (CYP3A4, CYP3A5 and EPHX1) and phase II (UGT2B7) metabolising enzymes have been assessed; additionally, the influence of transporters (ABCB1 and ABCC2), receptors (PXR) and other drug targets (voltage- gated Na+ channels) in CBZ clinical response has been evaluated. To date, these studies are controversial and require further investigations to clarify the functional role of these polymorphisms as potential biomarkers in regard to CBZ therapy.","PeriodicalId":11319,"journal":{"name":"Drug Metabolism and Drug Interactions","volume":"29 2","pages":"67-79"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/dmdi-2013-0046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32014126","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: 16

Venlafaxine pharmacokinetics focused on drug metabolism and potential biomarkers. 文拉法辛的药代动力学主要研究药物代谢和潜在的生物标志物。

Drug Metabolism and Drug Interactions Pub Date : 2014-01-01 DOI: 10.1515/dmdi-2013-0053

Paulo Magalhães, Gilberto Alves, Adrián Llerena, Amílcar Falcão

{"title":"Venlafaxine pharmacokinetics focused on drug metabolism and potential biomarkers.","authors":"Paulo Magalhães, Gilberto Alves, Adrián Llerena, Amílcar Falcão","doi":"10.1515/dmdi-2013-0053","DOIUrl":"https://doi.org/10.1515/dmdi-2013-0053","url":null,"abstract":"Venlafaxine (VEN) is one of the safest and most effective drugs used in the treatment of selective serotonin reuptake inhibitors-resistant depression, and thereby it is nowadays one of the most commonly prescribed antidepressants. Nevertheless, patients treated with antidepressant drugs including VEN have exhibited large inter-individual variability in drug outcomes, possibly due to the influence of genetic and nongenetic factors on the drug pharmacokinetics and/or pharmacodynamics. Among them, an increased interest has emerged over the last few years on the genetic and/or phenotypic profile for drug-metabolizing cytochrome P450 isoenzymes and drug transporters such as potential predictive pharmacokinetic-based biomarkers of the variability found in drug biodisposition and antidepressant response. The integration of some of these key therapeutic biomarkers with classic therapeutic drug monitoring constitutes a promising way to individualization of VEN's pharmacotherapy, offering to clinicians the ability to better predict and manage pharmacological treatments to maximize the drug effectiveness. Thus, this review provides an extensive discussion of the pharmacokinetics of VEN focusing in particular on metabolism issues, without forgetting the clinically relevant sources of pharmacokinetics variability (mainly the genetic sources) and aiming on the identification of phenotypic and/or genetic biomarkers for therapy optimization.","PeriodicalId":11319,"journal":{"name":"Drug Metabolism and Drug Interactions","volume":" ","pages":"129-41"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/dmdi-2013-0053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40292848","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: 34

Present status and perspective of pharmacogenetics in Mexico. 墨西哥药物遗传学研究现状与展望。

Drug Metabolism and Drug Interactions Pub Date : 2014-01-01 DOI: 10.1515/dmdi-2013-0019

Patricia Cuautle-Rodríguez, Adrián Llerena, Juan Molina-Guarneros

{"title":"Present status and perspective of pharmacogenetics in Mexico.","authors":"Patricia Cuautle-Rodríguez, Adrián Llerena, Juan Molina-Guarneros","doi":"10.1515/dmdi-2013-0019","DOIUrl":"https://doi.org/10.1515/dmdi-2013-0019","url":null,"abstract":"Drug costs account for up to 24% of the country's health expenditure and there are 13,000 registered drugs being prescribed. Diabetes is the main cause of death in the country, with over 85% of diabetic patients currently under drug treatment. The importance of knowing interindividual variability in drug metabolism on Mexican populations is thus evident. The purpose of this article is to provide an overlook of the current situation of pharmacogenetic research in Mexico, focusing on drug-metabolizing enzymes, and the possibility of developing a phenotyping cocktail for Mexican populations. So far, 21 pharmacogenetic studies on Mexican population samples (Mestizos and Amerindian) have been published. These have reported interindividual variability through phenotyping and/or genotyping cytochromes: CYP2D6, 2C19, 2C9, 2E1, and phase II enzymes UGT and NAT2. Some cytochromes with important clinical implications have not yet been phenotyped in Mexican populations. The development of a cocktail adapted to them could be a significant contribution to a larger knowledge on drug response variability at a lower price and shorter time. There are validated phenotyping cocktails that present several practical advantages, being valuable, safe, and inexpensive tools in drug metabolism characterization, which require only a single experiment to provide information on several cytochrome activities.","PeriodicalId":11319,"journal":{"name":"Drug Metabolism and Drug Interactions","volume":"29 1","pages":"37-45"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/dmdi-2013-0019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31810110","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: 16

Interaction of vitamin K antagonists and trimethoprim-sulfamethoxazole: ignore at your patient's risk. 维生素K拮抗剂与甲氧苄啶-磺胺甲恶唑的相互作用:忽略患者的风险。

Drug Metabolism and Drug Interactions Pub Date : 2014-01-01 DOI: 10.1515/dmdi-2013-0049

Sarah Fetterman Hale, Timothy S Lesar

{"title":"Interaction of vitamin K antagonists and trimethoprim-sulfamethoxazole: ignore at your patient's risk.","authors":"Sarah Fetterman Hale, Timothy S Lesar","doi":"10.1515/dmdi-2013-0049","DOIUrl":"https://doi.org/10.1515/dmdi-2013-0049","url":null,"abstract":"The aim of the study was to summarize available literature regarding the interaction between vitamin K antagonists (VKAs) and trimethoprim-sulfamethoxazole (co-trimoxazole, TMP-SMX), and to provide recommendations for managing patient risk from this interaction. Data sources were English-language publications in the medical literature and Internet databases. Relevant publications that directly or indirectly addressed the VKA-TMP-SMX interaction were selected and reviewed. The mechanism of the VKA-TMP-SMX interaction, frequency of concurrent use, effect on international normalized ratio (INR), increased risk of bleeding, and strategies for risk reduction are summarized. The concurrent use of VKA and TMP/SMX rapidly and consistently raises INR and is associated with a two- to five-fold increase in bleeding. Concurrent use of VKA and TMP-SMX should be avoided when possible. When VKA and TMP-SMX are co-prescribed, VKA dose reduction is usually required. Patient education as well as early and frequent INR monitoring is recommended to reduce risk from this interaction.","PeriodicalId":11319,"journal":{"name":"Drug Metabolism and Drug Interactions","volume":"29 1","pages":"53-60"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/dmdi-2013-0049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31864497","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: 8

Drug metabolising enzyme polymorphisms in Middle- and Eastern-European Slavic populations. 中欧和东欧斯拉夫人群的药物代谢酶多态性。

Drug Metabolism and Drug Interactions Pub Date : 2014-01-01 DOI: 10.1515/dmdi-2013-0052

Jaroslav A Hubacek

{"title":"Drug metabolising enzyme polymorphisms in Middle- and Eastern-European Slavic populations.","authors":"Jaroslav A Hubacek","doi":"10.1515/dmdi-2013-0052","DOIUrl":"https://doi.org/10.1515/dmdi-2013-0052","url":null,"abstract":"Inter-individual differences in genes for drug metabolising enzymes and drug transporters are important for understanding efficacy in drug therapy. These differences are important both for the timely estimation of the dosage that should be prescribed to a patient and for the detection of individuals who are prone to side effects from the drug at normal doses. This review summarises the literature concerning the gene variants within nine major drug metabolising enzymes and drug transporters (i.e., CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, and MDR-1) in the Middle European region. Notably, published data are not extensive, and most studies were performed on relatively low numbers of individuals. No country has a complete coverage of all genes. Two variants (C2677T/A and C3435T) within the multidrug resistance-1 (MDR-1) gene and variants within the CYP2C9 gene were analysed within most Slavic populations. Nevertheless, even from this incomplete coverage (where unexpectedly high variability was at times seen both between and within populations), it could be extrapolated that the variants within the drug metabolising enzyme genes are present in roughly the same frequencies as in neighbouring countries.","PeriodicalId":11319,"journal":{"name":"Drug Metabolism and Drug Interactions","volume":"29 1","pages":"29-36"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/dmdi-2013-0052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31952834","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

Pregnane X receptor (PXR)--a contributor to the diabetes epidemic? 妊娠X受体(PXR)-糖尿病流行的一个贡献者?

Drug Metabolism and Drug Interactions Pub Date : 2014-01-01 DOI: 10.1515/dmdi-2013-0036

Janne Hukkanen, Jukka Hakkola, Jaana Rysä

引用次数: 39