Ellis S. Grollman Lecture Brings Leaders in Pharmaceutical Sciences to SOP

Leslie Benet, PhD, professor and former chair of the Department of Bioengineering and Therapeutic Sciences at the University of California, San Francisco (UCSF), delivers keynote address.

By Malissa Carroll
November 15, 2012

Each year, the University of Maryland School of Pharmacy hosts the Ellis S. Grollman Memorial Lecture to bring outstanding leaders in pharmaceutical and basic sciences to speak with faculty, staff, and current students. This year’s lecture included talks from professionals in academia, industry, and government about current trends in drug development.

“The School of Pharmacy is fortunate to have donors and supporters who allow us to bring these types of events to the School every year,” said Natalie D. Eddington, PhD, FAAPS, FCP, dean and professor of the School. “Our endowed lectures allow us to host renowned scientists, practitioners, academics, and policy experts to speak with our faculty, staff, and students about areas of interest and hot topics in the field.”

This year marked the first time that the Grollman Lecture hosted a series of presentations for participants to attend, culminating in a keynote address by Leslie Benet, PhD, professor and former chair of the Department of Bioengineering and Therapeutic Sciences at the University of California, San Francisco (UCSF), founder and first president of the American Association of Pharmaceutical Scientists, and one of the most highly cited pharmacologists worldwide.

“The Department of Pharmaceutical Sciences at the School of Pharmacy spans the whole spectrum of drug development,” says Andrew Coop, PhD, professor and chair of the Department of Pharmaceutical Sciences. “This is reflected in the wonderful series of presentations delivered during this year’s Grollman Lecture, which included all of the major players in the collaborative environment of drug development: academia, industry, and the Food and Drug Administration.”

The first presenter of the day was Kimberley Lentz, PhD ‘00, senior principal scientist in metabolism and pharmacokinetics at Bristol-Myers Squibb. Her presentation, entitled “Can Optimal ADME Properties Alone Ensure Successful Drug Products?”, discussed the pharmaceutical industry’s renewed focus on analyzing the potency of pre-clinical drug candidates, which, it has been discovered, is likely the best predictor for maintaining a safe, yet efficacious drug dose. This practice, Lentz remarked, is now used in place of the outdated trend that focused only on improving the absorption, distribution, metabolism, and excretion (ADME) properties of these drugs.

“When I was a student at the School of Pharmacy in the 1990s, we thought that computational chemistry was going to revitalize the pharmaceutical industry. We were going to create billions of molecules to help us significantly increase the number of drugs available on the market,” said Lentz. “However, what happened was that chemists generated these large compound libraries full of molecules that had terrible solubility and permeability. These molecules had no chance for adequate dissolution or absorption.”

The second presentation, delivered by Robert Lionberger, PhD, chemist in the Office of Generic Drugs at the Food and Drug Administration (FDA), discussed the continued evolution of bioequivalence methods used by the FDA to ensure that generic drugs meet patients’ expectations, including new methods now specifically used to test narrow therapeutic index drugs, those drugs in which little difference exists between the toxic and therapeutic dose.

The School of Pharmacy’s own James E. Polli, PhD, professor and Ralph F. Shangraw/Noxell Endowed Chair in Industrial Pharmacy and Pharmaceutics, also gave a presentation, entitled “Drug Transporters in ADME Research.” This presentation examined adverse drug reactions and prodrugs, which are often designed to improve the absorption of oral medications in cases where the drug is poorly absorbed through the gastrointestinal tract. Polli specifically addressed a transporter called OCTN2 and how researchers may be able to use it to deliver drugs to certain tissue.

Later, Benet delivered the lecture’s keynote address, entitled “Predicting Drug Dosing Parameters for New Molecular Entities.”

Benet remarked that a great deal of interest exists today related to the development of non-clinical and clinical biomarkers that address efficacy, safety, as well as diagnostic procedures, but that validating these biomarkers as reputable indicators for therapeutic applications can be a very difficult task. He displayed data that his team collected for 22 drugs, and based on the data shown, he asserted that his team has correctly predicted the appropriate dosing and dosing interval for the stage in which drugs are studied in 12-24 subjects.

He conceded that there were three drugs for which his model did not work, but indicated the reason that these drugs did not coincide with his data might be that their identified biomarkers are inaccurate.

“The data for metformin and rosiglitazone don’t fall on the line, but what’s being used as the biomarker for these drugs? Decrease in glucose measurements,” said Benet. “There’s a lot of work right now that says that the effects of metformin, particularly on fat metabolism and hypertension, are not captured in a pharmacokinetic/pharmacodynamics (PKPD) model. The same is true for rosiglitazone.”

Though further study is needed, Benet asserts that great potential exists if pharmaceutical scientists are able to use his model to more accurately predict drug dosing parameters in the future.

About the Ellis S. Grollman Memorial Lecture:

Ellis S. Grollman was born on September 15, 1906 in Worton Point on the Eastern Shore of Maryland. After graduating from Baltimore City College, he attended the University of Maryland School of Pharmacy and received his PhG (Pharmacy Graduate) in 1926. He practiced as a hospital pharmacist at Johns Hopkins and Sinai Hospitals in Baltimore, and as a community pharmacist in Frederick, Ocean City, Gaithersburg, and Annapolis, MD. He died on December 18, 1982. The Ellis S. Grollman Lecture in the Pharmaceutical Sciences was established in 1983 by Grollman’s sister, Evelyn Grollman Glick, as an endowed memorial.

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