Drug transporters play a key role in the absorption, distribution, and elimination of many drugs, and they appear to be important determinants of therapeutic and adverse drug activities. Although a large body of data pertaining to drug transporters is available, there are few databases that inform drug developers, regulatory agencies, and academic scientists about transporters that are important in drug action and disposition. In this article, we inform the scientific community about the UCSF-FDA TransPortal, a new and valuable online resource for research and drug development.
[Show abstract][Hide abstract] ABSTRACT: Drug transporter proteins are of ever-increasing interest because of their role both in processes regulating pharmacokinetic properties of drugs (absorption, distribution, and elimination) and in the development of cellular drug resistance through decreased uptake or increased efflux of drugs in the target organ or tumor. Further understanding of the role of transporters in drug-drug interactions and identification of these proteins as possible therapeutic targets could contribute to improved treatment of a wide variety of diseases.
[Show abstract][Hide abstract] ABSTRACT: The kidney plays a vital role in the body's defense against potentially toxic xenobiotics and metabolic waste products through elimination pathways. In particular, secretory transporters in the proximal tubule are major determinants of the disposition of xenobiotics, including many prescription drugs. In the past decade, considerable progress has been made in understanding the impact of renal transporters on the disposition of many clinically used drugs. In addition, renal transporters have been implicated as sites for numerous clinically important drug-drug interactions. This review begins with a description of renal drug handling and presents relevant equations for the calculation of renal clearance, including filtration and secretory clearance. In addition, data on the localization, expression, substrates, and inhibitors of renal drug transporters are tabulated. The recent US Food and Drug Administration drug-drug interaction draft guidance as it pertains to the study of renal drug transporters is presented. Renal drug elimination in special populations and transporter splicing variants are also described. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 53 is January 06, 2013. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
[Show abstract][Hide abstract] ABSTRACT: A recent paper in this journal sought to counter evidence for the role of transport proteins in affecting drug uptake into cells, and questions that transporters can recognize drug molecules in addition to their endogenous substrates. However, there is abundant evidence that both drugs and proteins are highly promiscuous. Most proteins bind to many drugs and most drugs bind to multiple proteins (on average more than six), including transporters (mutations in these can determine resistance); most drugs are known to recognise at least one transporter. In this response, we alert readers to the relevant evidence that exists or is required. This needs to be acquired in cells that contain the relevant proteins, and we highlight an experimental system for simultaneous genome-wide assessment of carrier-mediated uptake in a eukaryotic cell (yeast).
Drug discovery today 11/2012; 18(5-6). DOI:10.1016/j.drudis.2012.11.008 · 6.69 Impact Factor
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