期刊
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
卷 7, 期 2, 页码 159-174出版社
TAYLOR & FRANCIS LTD
DOI: 10.1517/17425255.2011.547474
关键词
cisplatin; metformin; organic cation transporters; toxicity
资金
- Deutsche Forschungsgemeinschaft (DFG) [CI 107/4-1]
- Deutsche Krebshilfe (DKH) [108539]
Introduction: Membrane transporters are important determinants of in vivo drug disposition, therapeutic efficacy and adverse drug reactions. Many commonly used drugs are organic cations and substrates of organic cation transporters (OCTs). These transporters have a large binding site containing partially overlapping interaction domains for different substrates and are specifically distributed around the body. Consequently, drug interactions with these transporters can result in specific toxicity. Areas covered: This review describes the general properties of OCT and illustrates their importance for the development of important drug toxicities using the examples of metformin and cisplatin. Additionally, this review discusses the role of OCT polymorphisms in the modulation of these toxic effects. Expert opinion: Understanding how drugs interact with membrane transporters is pivotally important in explaining the mechanisms of specific toxicities and also in designing new drugs or new therapeutic protective protocols by specific competition at the transporter. Defining the pharmacogenomics of these transporters will be essential to personalized medicine, enabling physicians to choose drugs for patients based on efficacy, availability, cost, safety, tolerability and convenience.
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