Research overview

The Benet Lab focuses on explicating the blood level time course of drugs, their pharmacodynamic response, and drug-drug interactions that cannot be explained by a current theory.

Hypotheses are tested at the molecular and cellular level, studies are then carried out in animal gut and liver cells, isolated perfused animal organs, whole animal studies and then confirmed by clinical studies in humans.

Why now

Recent work has shown that the inability to predict drug metabolism using isolated hepatic or intestinal microsomes is due to the fact that for many substrates both uptake and efflux transporters control the access of substrates to these intracellular enzymes. Similarly, the inability to use allometric scaling across animal species to predict human drug metabolism is frequently due to a lack of knowledge about the differences in transporters between animals and man.

Our group has found that transporter function greatly influences the disposition of a number of commonly used drugs such as antibiotics, statins, hypoglycemic agents.

Giving the proper dose of a prescribed medication is crucial to ensure safety and effectiveness. Accurate calculations of how rapidly a drug is cleared from the body are key to an understanding how much drug is active in the body at a given time. Leslie Benet, PhD, was one of the creators and disseminators of the concept called clearance which serves as the basis for calculating how much of a prescribed drug to give a patient.

Benet, along with colleagues Malcolm Rowland, PhD, and Gary Graham, PhD, described the first models based on the clearance concept in 1973. They are now are in standard use. Unlike earlier ways of calculating drug dose, these models can be used to account for physiological differences that arise during disease or that exist among different patients.

Using the latest modeling software for modeling drug clearance, Benet and colleagues accounted for the effects of enzymes that metabolize drugs. His laboratory was the first to hypothesize and confirm that proteins known as drug transporters could control the access of drugs to these metabolic enzymes leading to the concept of transporter-enzyme interplay. Transporters are now a major focus of pharmacogenetic studies at UCSF and elsewhere, with research aimed at identifying important individual differences in drug metabolism.

Why here

The work of the Benet Lab is carried out at UC San Francisco, a global leader in pioneering scientific breakthroughs for healthcare. The Benet Lab is able to run in-silico, in-vitro and in-vivo experiments as well as human studies and is heavily involved in Translational Medicine, i.e., Bench to Bedside. The Benet Lab is part of the Department of Bioengineering and Therapeutic Sciences, a joint department of the UCSF School of Pharmacy and the UCSF School of Medicine, and works closely with the UCSF Clinical & Translational Science Institute (CTSI) helping to make research at UCSF smarter and faster.