UCSF Center for Quantitative Pharmacology kicks off with 2-day Mission Bay symposium

The new UCSF Center for Quantitative Pharmacology housed within the Department of Bioengineering and Therapeutic Sciences (BTS), a joint department of the Schools of Pharmacy and Medicine, will be inaugurated next week with a wide-ranging, 2-day conference, September 22 and 23, 2011 at William J. Rutter Center on UCSF’s Mission Bay campus.

The symposium, “Accelerating Predictive Drug Development through Innovations in Quantitative Pharmacology,” will bring together experts from UCSF, the pharmaceutical industry, and the U.S. Food and Drug Administration (FDA) to focus attention on the burgeoning field and help define its future.

Presentations and panels will address quantitative pharmacology in all of its applications from preclinical modeling and pharmacokinetic simulation (i.e., how our bodies process a medication) in drug development to pharmacometrics in clinical trials; and from the regulatory approval process to the role of the university and the BTS department in advancing education in the field.

“Each phase of drug development has quantitative methodologies associated with it,” says BTS and symposium co-chair Kathy Giacomini, PhD. “And the data behind each stage along the drug development pipeline are growing, so there’s more and more data and information that needs to be integrated.”

The new center, with its mission of research and education, will bring together faculty for cross-disciplinary research as well as developing courses in this key emergent discipline. It will also be competitive for potential grants from the National Institutes of Health, which has held 2 workshops on quantitative and systems pharmacology.

New Center reflects traditional UCSF strength

The new center is the latest step in UCSF’s significant and ongoing contributions to the field.

Since the 1970s, the School of Pharmacy’s Department of Pharmaceutical Chemistry has pioneered the use of computer modeling, simulations, and visualization in early drug discovery. This form of quantitative pharmacology is now widely used to virtually screen vast numbers of potential drug molecules (i.e., ligands) and rate how well they bind to—and potentially inhibit—errant proteins involved in disease processes.

Increasingly sophisticated programs, which account for molecules’ shifting shapes, charges, and solvation and which can be visualized in 3 dimensions, can rapidly find new drug prospects or, by associating target proteins via their ligands, new uses for existing drugs.

“It shortens that time,” explains Giacomini. “You’ve got some potential drug leads right away.”

Likewise, pre-clinical in vitro and animal testing, which examines the pharmacokinetics of a drug—how it is absorbed, distributed, metabolized, and excreted (ADME), is being accelerated via mathematical models and computer simulation of those processes and even increasingly complex physiologically based pharmacokinetic (PBPK) models of whole organisms. Today, School of Pharmacy computational chemists and biophysicists model and screen molecules for interactions with drug targets, efficient membrane diffusion, and susceptibility to efflux transporters—whether in cell walls or the blood-brain barrier. Meanwhile, labs here like Giacomini’s are researching how genetic variations encoding families of membrane transporters—proteins that affect the passage of drug molecules in and out of cells—affect responses, so this data is increasingly being included in ADME models, too.

“You can select your leads more quickly because they will not only have good drug interaction with the target, but also good pharmacokinetic properties,” notes Giacomini.

“These in silico [i.e., computer] models are really advancing as we put in data on the transporters, put in the enzymes—which activate or break down drug molecules—and begin to really predict with PBPK,” she says.

UCSF has also had a leadership role for several decades in parallel advances applying quantitative pharmacology and statistical models to the clinical testing and dosing of drugs for safety and efficacy in human subjects.

Center and Symposium part of Sheiner legacy

Next week’s conference is dedicated to the memory of the late Lewis B. Sheiner, MD (1940–2004), a UCSF faculty member of both the Schools of Pharmacy and Medicine, who devoted his career to developing and applying modeling and simulation to make both clinical trials of prospective drugs and dosing of approved drugs for individual patients more efficient and effective.

Among his many contributions, Sheiner’s statistical modeling helped shape the design of clinical trials and the interpretation of their findings by integrating factors such as dose timing, drug concentrations, drug tolerance and delayed effects—combining pharmacodynamic data (the effect of drug concentrations on the body) with pharmacokinetic data (how the body handles and alters the drugs put into it via ADME).

Sheiner’s work contributed to how drug trial design and data are reviewed and analyzed by FDA scientists. Carl Peck, MD, now a UCSF faculty member and founding director of the School of Pharmacy’s Center for Drug Development Science (CDDS) in Washington, DC, was formerly the director of the FDA’s Center for Drug Evaluation and Research where he brought Sheiner’s and others’ scientific framework and tools to bear.

Peck played a key role with other CDDS colleagues in modernizing the FDA regulatory process by applying computer modeling and simulation to forecasting and clarifying clinical trial outcomes. He will be moderating 2 symposium panels, discussing the application of pharmacometrics to drug development and regulatory approval.

Indeed, Sheiner’s legacy goes beyond quantitative pharmacology in clinical research and regulatory science. A bequest from his estate has endowed 2 graduate fellowships in quantitative pharmacology as well as providing support for next week’s symposium.

Further inquiries, contact Jaime Kenyon at [email protected].