| CYP2C metabolism of oral antidiabetic drugs--impact on pharmacokinetics, drug interactions and pharmacogenetic aspects. | |
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MedLine Citation:
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PMID: 23153186 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The cytochrome P4502C enzymes account for the metabolism of approximately 20% of therapeutic drugs including certain oral antidiabetic drugs (OADs). AREAS COVERED: This review focuses on the effect of CYP2C enzymes on metabolism of sulphonylureas (SUs), meglitinides, and thiazolidinediones (TZDs) discussing their impact on pharmacokinetics, drug interactions and toxicological profiles. Pharmacogenetic aspects reflecting individual gene variants and variable drug effects are also considered. EXPERT OPINION: Genetic polymorphisms of CYP2C9 enzymes (*2/*2, *2/*3, *3/*3) influence the glycaemic response to SUs and impair their substrate metabolism. Restricted data from small-sized studies with heterogenous definitions of hypoglycaemia revealed no clear association between CYP2C9 genotypes and the risk of hypoglycaemia. Functional polymorphisms of CYP2C8- and CYP2C9 drug metabolizing genes affect markedly pharmacokinetics of meglitinides. Compared to wild-type carriers, patients treated with TZDs and carrying the common CYP2C8*3 and *4 variants showed a reduced glycaemic control. The strong CYP2C8 and OATP1B1 inhibitor gemfibrozil increases substantially the plasma concentrations of repaglinide and TZDs. Numerous metabolic drug interactions exist between SUs and commonly prescribed drugs, especially anti-infectives. The complex pharmacokinetic and pharmacogenetic properties and the unfavourable short and long term risk profile of glibenclamide and glimepiride raise the question whether their use can be justified any longer. |
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Authors:
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Andreas Holstein; Winfried Beil; Peter Kovacs |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: Expert opinion on drug metabolism & toxicology Volume: 8 ISSN: 1744-7607 ISO Abbreviation: Expert Opin Drug Metab Toxicol Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-11-16 Completed Date: 2013-04-25 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 101228422 Medline TA: Expert Opin Drug Metab Toxicol Country: England |
Other Details:
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Languages: eng Pagination: 1549-63 Citation Subset: IM |
Affiliation:
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Lippe-Detmold Hospital, First Department of Medicine, Röntgenstr. 18, Detmold, 32756, Germany. Andreas.Holstein@t-online.de |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Benzamides / adverse effects, pharmacokinetics Blood Glucose / analysis Carbamates / adverse effects, pharmacokinetics Cytochrome P-450 Enzyme System / genetics, metabolism* Drug Interactions Gemfibrozil / adverse effects, pharmacokinetics Humans Hypoglycemic Agents / pharmacokinetics*, therapeutic use* Metabolic Detoxication, Drug Pharmacogenetics* Piperidines / adverse effects, pharmacokinetics Polymorphism, Single Nucleotide Sulfonylurea Compounds / adverse effects, pharmacokinetics Thiazolidinediones / adverse effects, pharmacokinetics |
| Chemical | |
Reg. No./Substance:
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0/Benzamides; 0/Blood Glucose; 0/Carbamates; 0/Hypoglycemic Agents; 0/Piperidines; 0/Sulfonylurea Compounds; 0/Thiazolidinediones; 0/cytochrome P-450 CYP2C subfamily; 135062-02-1/repaglinide; 25812-30-0/Gemfibrozil; 8V6OK1I088/meglitinide; 9035-51-2/Cytochrome P-450 Enzyme System; 93479-97-1/glimepiride |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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