Clinical Pharmacology & Therapeutics

doi: 10.1038/clpt.2012.174pmid: N/A

Sprowl, J A; Sparreboom, A

doi: 10.1038/clpt.2012.167pmid: 23085872

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.

Waldman, S A; Terzic, A

doi: 10.1038/clpt.2012.151pmid: 23085873

Pharmacometrics and systems pharmacology are emerging as principal quantitative sciences within drug development and experimental therapeutics. In recognition of the importance of pharmacometrics and systems pharmacology to the discipline of clinical pharmacology, the American Society for Clinical Pharmacology and Therapeutics (ASCPT), in collaboration with Nature Publishing Group and Clinical Pharmacology & Therapeutics, has established CPT: Pharmacometrics & Systems Pharmacology to inform the field and shape the discipline.

Laffman‐Johnson, Elise

doi: 10.1038/clpt.2012.173pmid: N/A

doi: 10.1038/clpt.2012.169pmid: N/A

Morrissey, K M; Wen, C C; Johns, S J; Zhang, L; Huang, S‐M; Giacomini, K M

doi: 10.1038/clpt.2012.44pmid: 23085876

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.

Fromm, M F

doi: 10.1038/clpt.2012.145pmid: 23085877

Therapy with two or more drugs is more the rule than the exception, particularly in aging societies. Drug–drug interactions are frequently undesirable and may lead to increased toxicity and mortality. Inhibition of transporters is one major mechanism underlying drug–drug interactions. The myriad of potential drug combinations makes it very challenging to predict drug–drug interactions. This Commentary discusses potential advantages and limitations of endogenous compounds for predicting transporter‐mediated drug–drug interactions.

Sharma, M R; Maitland, M L; Ratain, M J

doi: 10.1038/clpt.2012.99pmid: 23085878

Simulations based on disease‐progression models and phase II trial results can predict phase III results and have the potential to improve oncology drug development by informing end‐of‐phase II decisions (EOP2Ds). Many barriers impede effective use of modeling and simulation (M&S) for EOP2Ds in oncology: concerns about model validity, lack of access to M&S results and patient‐level data, limited awareness of M&S among academic oncologists, and inexperience fitting M&S into the drug development timeline.

Benet, L Z

doi: 10.1038/clpt.2012.165pmid: 23085879

Understanding the metabolic, transporter, and genetic influences on the disposition of drugs used in chemotherapy is critical to individualization of drug therapy. Recognition of the importance of transporter–enzyme interplay, in which genetic variants of drug uptake transporters can change drug metabolism when the enzymes are unchanged, is an important advance in predicting appropriate drug dosage regimens for the individual patient.

Zamek‐Gliszczynski, M J; Hoffmaster, K A; Tweedie, D J; Giacomini, K M; Hillgren, K M

doi: 10.1038/clpt.2012.126pmid: 23085880

The Second International Transporter Consortium (ITC) Workshop was held with the purpose of expanding on previous white‐paper recommendations, discussing recent regulatory draft guidance documents on transporter–drug interactions, and highlighting transporter‐related challenges in drug development. Specific goals were to discuss additional clinically relevant transporters (MATEs, MRP2, BSEP) and best‐practice methodologies and to re‐evaluate ITC decision trees based on actual case studies. The outcome of the workshop will be a series of white papers targeted for publication in 2013.