Understanding Hepatobiliary Disposition:The Importance of an Integrative Platform in Evaluating Transporter Interactions

Date: June 03 2015
Presenter(s): Dr. Kenneth R. Brouwer, Ph.D.

Webinar presented on June 3rd, 2015 by Kenneth R. Brouwer, Ph.D., RPh., Chief Scientific Officer at QualystTransporter Solutions, Durham, North Carolina USA

Summary of the presentation

In addition to its inherent pharmacological activity, a drug must cross multiple barriers to be effective in vivo, and to eventually be eliminated from the body. Transporters play a key role as the gate keepers at these biological membranes and control entry and exit across membranes and organs. The liver is a major organ of elimination, and is responsible for the excretion of drug and/or metabolites into the bile.

Transport characteristics of a drug and its metabolites are important in determining their potential for hepatic uptake, intracellular concentration, biliary excretion, and transporter based drug interactions. Sandwich-cultured hepatocytes offer many advantages over single transporter models for evaluation of transporter function and regulation.

Hepatocyte quality (fresh or cryopreserved), plating parameters, and culture conditions can have a significant impact on transporter expression and function, therefore, all sandwich-cultured systems are not equivalent. At Qualyst Transporter Solutions, we have applied our patented technology to identify lots of cryopreserved human hepatocytes that are Transporter Certified™, and when plated and cultured under our conditions are optimal for the evaluation of transporter function. B-CLEAR®technology and Transporter Certified™ hepatocytes can be used to answer key questions on the importance of transporters for your compound in drug discovery and development.

Key concepts discussed in this webinar will include:

  • Important factors that affect the quality of transporter data derived from sandwich-cultured hepatocytes
  • Description and applications of B-CLEAR® technology
  • Importance of an integrated platform in evaluating acute and chronic transporter interactions


Dr. Kenneth R. Brouwer is Chief Scientific Officer at QualystTransporter Solutions, a company focused on providing solutions to transporter questions that arise during drug discovery and development in the areas ofhepatic drug transport (B-CLEAR®), drug interactions, and evaluation of hepatotoxicity. Prior to this, Dr. Brouwer served as Executive Director, Drug Metabolism and Pharmacokinetics, at PPD Discovery, USA, where he had responsibility for overseeing the scientific and administrative operations within the preclinical groups at PPD Discovery, including the areas of metabolism, pharmacokinetics, toxicology; absorption technologies, and Pharmazyme groups. Before joining PPD Discovery, he served as Director, Preclinical Development, Drug Metabolism and Pharmacokinetics at GlaxoSmithKline. In addition, he was responsible for the drug metabolism and pharmacokinetics developability strategy leading to candidate selection, review of drug candidate project plans prior to candidate selection, and developing and implementing process to ensure a smooth transition from candidate selection to full development.Over his 18 year tenure at GlaxoSmithKline, Dr Brouwer held positions of increasing responsibility in both Clinical Pharmacokinetics and Drug Metabolism. Dr. Brouwer has successfully lead and directed large international multidisciplinary project teams to support the product development of 4 high priority development candidates. He has been the Drug Metabolism Project Team Leader for 12 Development compounds and 6 Discovery compounds. He has served as the Pharmacokinetics and Drug Metabolism expert at FDA panel presentations for GlaxoSmithKline, and has authored or co-authored over 400 company reports to support ERC, CTX, IND, NDA and MAA regulatory submissions. Dr. Brouwer has over 60 publications in peer reviewed journals, and is the holder of 3 patents. Dr. Brouwer serves on the Editorial Advisory Board for the Journal of Pharmaceutical Sciences, and is a reviewer for several additional journals. Dr. Brouwer is an adjunct faculty member in the Division of Molecular Pharmaceutics at the School of Pharmacy, University of North Carolina.