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- W4280495445 abstract "The role of membrane transporters on pharmacokinetics (PK), drug-drug interactions (DDIs), pharmacodynamics (PD), and toxicity of drugs has been broadly recognized. However, our knowledge of modulation of transporter expression and/or function in diseased patient population or specific populations such as pediatrics or pregnancy is still emerging. This white paper highlights recent advances in studying the changes in transporter expression and activity in various diseases (i.e., renal and hepatic impairment, cancer) and some specific populations (i.e., pediatrics and pregnancy) with the focus on clinical implications. Proposed alterations in transporter abundance and/or activity in diseased and specific populations are based on 1) quantitative transporter proteomic data and relative abundance in specific populations versus healthy adults, 2) clinical PK, and emerging transporter biomarker and/or pharmacogenomic data, and 3) physiologically based pharmacokinetic (PBPK) modeling and simulation. The potential for altered PK, PD and toxicity in these populations needs to be considered for drugs and their active metabolites in which transporter-mediated uptake/efflux is a major contributor to their absorption, distribution, and elimination pathways and/or associated DDI risk. In addition to best practices, this white paper discusses current challenges and knowledge gaps to study and quantitatively predict the effects of modulation in transporter activity in these populations, together with the perspectives from the International Transporter Consortium (ITC) on future directions." @default.
- W4280495445 created "2022-05-22" @default.
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- W4280495445 date "2022-06-21" @default.
- W4280495445 modified "2023-09-29" @default.
- W4280495445 title "Clinical Implications of Altered Drug Transporter Abundance/Function and <scp>PBPK</scp> Modeling in Specific Populations: An <scp>ITC</scp> Perspective" @default.
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