Dr. Adrian Ray – Transporter-Mediated Drug Interactions with Non-Drugs – How Common Are They?

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    Organizer: Optivia Biotechnology Inc.

    Time: Wed, May 10, 2017 10:00 AM - 11:30 AM PDT

    Cost: Free

  • Transporters play an important role in the disposition of endobiotics, dietary nutrients and environmental toxins. This is evident in the clinical utility of drugs that target transporters including gliflozins, inhibiting glucose renal reabsorption by sodium glucose transporter 2 (SGLT2, SLC5A2), uricosurics, inhibiting uric acid renal reabsorption by urate transporter 1 (URAT1, SLC22A12) and antidepressants, inhibiting serotonin (SERT, SLC6A4) and norepinephrine (NET, SLC6A2) transporters in the brain. There has been an increasing awareness of the potential for transporter inhibition to cause adverse events by blocking physiologic processes illustrated by recommendations for assessing inhibition of the bile salt efflux transporter (BSEP, ABCB11) due to the association of inhibition of this transporter with hepatic cholestasis and idiosyncratic liver toxicity. The stoppage of clinical development of janus kinase 2 inhibitor fedratinib during Phase 3 clinical testing in late 2013 due to the observation of Wernicke Encephalopathy, a condition associated with thiamine deficiency, highlighted the risk of drug interactions with vitamins. It would not be surprising if the frequency of interactions of drugs with non-drugs is underappreciated. Of the over 400 transporters in the human body, only a handful are routinely studied per regulatory guidance documents and these transporters have been selected almost exclusively for their established involvement in drug-drug interactions. Also, only select non-drugs are routinely monitored during clinical studies and, of these, a number of drugs have been found to interfere with the transport of the safety markers creatinine and bilirubin. Our understanding of the potential of drugs to affect the physiologic roles of transporters promises to increase with the use of unbiased metabolomics and more holistic in vitro systems.

  • Dr. Adrian Ray

    Adrian S. Ray, Ph.D.,

    Gilead Sciences, Inc.

    Dr. Adrian Ray is Senior Director Clinical Research at Gilead Sciences, Inc. where he has been a researcher for over 14 years. He received his undergraduate degree from the University of California Santa Cruz and Ph.D. from Yale University. His accomplishments include over 90 peer-reviewed publications, serving as a primary responder at 3 FDA advisory committee meetings, and being the recipient of the 2014 William H. Prusoff award presented by the International Society for Antiviral Research. Adrian’s work has included studies to understand the mechanisms for transporter-mediated effects of drugs on creatinine, thiamine, bile acids, bilirubin and phosphate.