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Bente SteffansenBente Steffansen, Ph.D., is associate professor in Biopharmacy and program director for Pharmacy Education at the Faculty of Health and Medical Sciences, University of Copenhagen. She concentrates her research on optimizing drug bioavailability and drug targeting, including development of experimental in vitro models relevant for regulatory sciences.

Membrane transporters play important roles throughout drug development, from discovery to life-cycle management. Understanding their role in pharmacology and pharmacokinetics leads to new drug targets and/or delivery strategies and may even play a role in life-cycle management and refinement of treatment protocols.

One example is the glucose transporter 2 (SGLT2). SGLT2 is responsible for 90% of the glucose reuptake in the kidney. The drug substances danagliflozin and dapagliflozin inhibit SGLT2-mediated glucose reuptake, thereby increasing the renal glucose excretion and decreasing blood glucose, making SGLT2 a suitable target for diabetes 2 treatment. An example of understanding the pharmacokinetic profile of a drug interacting with an intestinal transporter is the role of the proton-coupled amino acid transporter (PAT1) in the intestinal absorption of the drug candidate gaboxadol. Strategies targeting the proton-coupled di/tri-peptide transporter, PEPT1, may lead to prodrugs with increased bioavailability of the bioactive drug.

Identifying the genetics of transporters will result in meaningful personalized treatments if genetic variations of the transporter influence medical treatment. An example is genetic variation, i.e., single nucleotide polymorphism (SNP), in the organic anion transporting polypeptide 1B1 (OATP1B1), which has been shown to influence the plasma profile (AUC) of drug substrates such as statins. In the medical treatment with statins it is recommended to take the individual patient SNPs of OAP1B1 into account.

A greater awareness of transporters in drug development processes is an important key to new and personalized medicine! In the new book in the AAPS Advances in the Pharmaceutical Sciences series Transporters in Drug Development: Discovery, Optimization, Clinical Study and Regulation, leading scientists in the transporter field describe the many roles of transporters in modern drug development and use. The volume gives a comprehensive overview of the critical importance of membrane transporters nowadays in the process of drug discovery, pharmaceutical development, including regulatory considerations and last but not least: treatment schedules.

The recently obtained insights in transporters have changed our view on the performance of drugs and the drug discovery and development process, and a lot more is coming. Stay tuned!