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Genomics and Drug Transporters and Application in Drug Discovery, Delivery, and Development

  • Robert Gharavi
  • Hazem E. Hassan
Chapter

Abstract

Drug transporters are membrane-bound proteins known to regulate the entry (influx) and exit (efflux) of both exogenous (drugs) and endogenous molecules in various tissues throughout the body [1, 2]. They have emerged as key determinants in the absorption, distribution, metabolism, excretion, and toxicity of a number of drug molecules [2, 3]. Furthermore, they have been identified as sources of harmful inherited diseases, drug-drug interactions (DDIs), and increased resistance and sensitivity to various chemotherapy, antiviral, and antibiotic treatments [4–9]. Regulatory health agencies from across the globe have released official guidance in recent years highlighting the emerging importance of transporters in the disposition of drugs and the need to thoroughly investigate their drug interactions [10–12]. Most genes encoding drug transporters are polymorphic, resulting in phenotypes that can vary greatly in their levels of expression, protein folding, membrane localization, and transporter efficiencies [3, 13]. These phenotypic differences can ultimately result in major interindividual variabilities in response to identical drug molecules (i.e., pharmacokinetics (PK), pharmacodynamics (PD), safety, and efficacy). To date, there are a myriad of reports of how a single nucleic acid base pair change in a transporter gene can result in markedly different patient responses to the same molecules [3]. As a result, the US Food and Drug Administration (FDA) currently requires pharmacogenomic biomarker information included in the drug labeling of a list of approved therapies [14]. Therefore, there is an evolving interest in the role that drug transporter polymorphisms may play in predicting individual responses and understanding interethnic differences in drug therapies.

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Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Pharmacokinetics and Biopharmaceutics Laboratory (PBL), Department of Pharmaceutical SciencesUniversity of Maryland School of PharmacyBaltimoreUSA
  2. 2.Faculty of PharmacyHelwan UniversityHelwanEgypt

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