The William B. Abrams Lecture is a joint educational initiative of ASCPT and the FDA. The lecture series, supported in part by The Merck Company Foundation, was established in 1999 to honor William B. Abrams, MD, an ASCPT president from 1975 to 1976.
Among his many accomplishments, Dr. Abrams worked at the FDA as the first special government employee to establish the Center for Drug Evaluation and Research Staff College and develop its curriculum. He also had a distinguished career in the pharmaceutical industry as a longtime employee of Merck Research Laboratories.
For more than 10 years, ASCPT and the FDA have invited experts from academia, industry, and government to discuss advances in clinical pharmacology and drug development. These scientists have excelled in their specialty areas and are some of the most highly esteemed clinical pharmacologists in the field. Their presentations convey novel information and perspectives on fundamental aspects of clinical pharmacology. Previous lectures have included speakers from the Mayo Clinic, University of California, Children's Mercy Hospitals and Clinics, and the National Institutes of Health.
2018 ASCPT & FDA William B. Abrams Lecture
The 2018 ASCPT & FDA William Abrams Lecture Award recipient is Kim L. R. Brouwer, PharmD, PhD from the Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill.
The lecture took place on Wednesday, May 23, 2018.
The 2018 lecture is titled: Altered Hepatic Transport Due to Liver Disease and Drug Interactions: Implications for Drug Development
Transport proteins mediate the hepatic uptake and excretion of many endogenous and exogenous compounds including bile acids, drugs and metabolites. Liver disease [e.g., nonalcoholic steatohepatitis (NASH)] and drug interactions can markedly impact hepatic transporter function and drug disposition, which may influence the efficacy and/or toxicity of medications. Hepatic transporters that play a critical role in bile acid homeostasis in humans, including the novel basolateral efflux transporter OSTα/β, will be reviewed. The application of mechanistic modeling and simulations based on data generated in human sandwich-cultured hepatocytes to assess the impact of drug interactions (induction or inhibition) on hepatocellular bile acid exposure will be highlighted. The interplay between bile acid exposure, hepatic transporter dynamics, and regulation of transporters to protect hepatocytes from bile acid-mediated toxicity will be discussed. Human-relevant cell-based systems and computational approaches, including systems pharmacology modeling, are valuable tools that drug development scientists can use to identify compounds with cholestatic potential, and to predict susceptibility factors for drug-induced liver injury.
Supported by NIH R01 GM041935 and NIH R35 GM122576
- Identify the hepatic transport proteins localized on the basolateral and apical (canalicular) membranes of human hepatocytes that are responsible for the uptake and efflux of endogenous compounds, drugs and metabolites.
- List factors that may modulate hepatic transporter expression and/or function.
- Describe changes in hepatic transporter protein function in patients with nonalcoholic steatohepatitis (NASH) and the potential implications for systemic and hepatic exposure to drugs and metabolites.
- Identify potential mechanisms of bile acid-mediated drug-induced liver injury.
- List model systems that can be used to investigate the hepatic transport of drugs and metabolites, and describe advantages and limitations of each.
- Ali I, Slizgi JR, Kaullen JD, Ivanovic M, Niemi M, Stewart P, Barritt A and Brouwer KLR: Transporter-Mediated Alterations in Patients with NASH Increase Systemic and Hepatic Exposure to an OATP and MRP2 Substrate. Clin Pharmacol Ther, in press, 2017.
- Yang K, Guo C, Woodhead JL, St. Claire RL, Watkins PB, Siler SQ, Howell BA and Brouwer KLR: Sandwich-Cultured Hepatocytes as a Tool to Study Drug Disposition and Drug-Induced Liver Injury. J Pharm Sci 105:443-459, 2016.
- Yang K, Woodhead JL, Watkins PB, Howell BA and Brouwer KLR: Systems Pharmacology Modeling Predicts Delayed Presentation and Species Differences in Bile Acid-Mediated Troglitazone Hepatotoxicity. Clin Pharmacol Ther, 96:589-598, 2014.
If you have any questions about the ASCPT & FDA Abrams Award please contact Megan McBeath Hay.