Industry pioneer Benet receives premier pharmacology prize, honorary doctorate

Pharmacology pioneer Leslie Z. Benet, PhD, who established the foundation for much of what is now known about the rate at which drugs are metabolized in the body, was honored with the premier prize from the American Society for Clinical Pharmacology and Therapeutics (ASCPT). In the same week, he also was awarded an honorary doctorate from Catholic University of Leuven, Belgium.

Dr. Benet received the Oscar B. Hunter Memorial Award in Therapeutics - which recognizes lifetime achievement in drug research, contributions to patient care, and teaching - at an award presentation in Atlanta during the ASCPT annual meeting on March 20.Dr. Benet presented a lecture summarizing work that has led to a better understanding of drug metabolism and disposition, dosing for individual patients, and drug toxicity.

The recognition included an honorarium and plaque-mounted medal.

Dr. Benet, 72, was one of the creators and disseminators of the concept called clearance, which serves as the basis for calculating the dose of a prescribed drug to give to a patient. An accurate calculation of how rapidly a drug is cleared from the body is key to understanding the amount of a drug that is active in the body at a given time.

Dr. Benet, along with colleagues Malcolm Rowland, PhD, and Gary Graham, PhD, described the first models based on the clearance concept in 1973, which 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.

In modeling drug clearance, Dr. Benet and colleagues accounted for the effects of enzymes that metabolize drugs. They were the first to consider the effects of proteins known as drug transporters, which help determine whether and when drugs are excreted. Transporters now are a major focus of pharmacogenetic studies at the University of California, San Francisco (UCSF) and elsewhere, with research aimed at identifying important individual differences in drug metabolism.

Dr. Benet is currently a professor in the Department of Bioengineering and Therapeutic Sciences in the UCSF schools of pharmacy and medicine. He has been a member of the School of Pharmacy faculty since 1969, and he chaired its Department of Biopharmaceutical Sciences from 1978 to 1998.

Since stepping down as department chair, Dr. Benet has intensified his research and established four private companies and partnerships to better translate his discoveries into widespread use. Most recently, Dr. Benet helped found and currently serves as chair of the Scientific Advisory Board of Hurel Corp., with the aim of commercializing the “man on a chip” concept. This concept promises to be an efficient and more accurate early screening technique for evaluating the efficacy and toxicity of new drug candidates, Dr. Benet said. With the use of “microfluidic” techniques, cells plated onto a plastic device are bathed in a liquid growth medium that acts like the blood supply in providing nutrients.

Compared with other lab techniques, the device allows for a more realistic evaluation of the metabolism and elimination of pharmaceuticals. It also provides a way to gain new insight into how animal and human responses to particular drugs may be similar or different, and can potentially lead to a very marked decrease in the use of animals in drug development, Dr. Benet said.

In his ongoing UCSF research, Dr. Benet is investigating the ways metabolizing enzymes and transporters can act together to speed elimination of immunosuppressive, anti-cancer, anti-HIV, and anti-parasite drugs. An additional focus is on developing measures to evaluate the ways in which drugs influence immune responses.

Dr. Benet has received many honors and awards during his career. He was elected to membership in the Institute of Medicine of the National Academy of Sciences in 1987 and has been awarded seven honorary doctorates from distinguished universities.

The honorary doctorate from Catholic University was awarded on March 26 in recognition of Dr. Benet’s “innovative research and widespread influence as a driving force in many areas of the pharmaceutical world.”

A symposium titled “Recent Progress in Drug Disposition Science, Let’s Think Mechanisms” was held on March 25 to honor Dr. Benet. He presented the closing lecture, “Transporter-Enzyme Interplay in Predicting Drug Absorption and Disposition.”