Benet receives Magic Bullet Lifetime Achievement Award

Leslie Z. Benet, PhD, UCSF School of Pharmacy faculty member, received the 2008 Paul Ehrlich Magic Bullet Lifetime Achievement Award at the Second World Conference on Magic Bullets, which convened in Nuremberg, Germany, in early October. The award recognized Benet's scientific accomplishments in pharmacokinetics and pharmacodynamics. Benet was one of 7 recipients.

The conference brought together more than 1,500 clinical and pharmacological scientists from 100 countries. This year's meeting celebrated the 100th anniversary of magic bullet visionary Paul Ehrlich's Nobel Prize.

In announcing the conference, the organizers stated, "In his Nobel Lecture on December 11th, 1908, Paul Ehrlich laid out the foundation of chemotherapy and the use of drugs to cure patients. He coined the term ‘magic bullets', and this term has remained in science as well as in the lay world for particularly important and clinically efficacious drugs."

Ehrlich used the term in referring to his search for drug treatments that, without destroying healthy tissue, could find and target agents of disease within the body. This has proved a quest worthy of a century of continual effort by biomedical researchers. This year's World Conference on Magic Bullets focused on ways to better take into account pharmacokinetics and pharmacodynamics in developing and using magic bullets. A goal is to more rationally use knowledge of drug transport and metabolism to develop targeted drugs and individualize drug therapy. The conference was hosted by the German Association of Pharmaceutical Scientists and the International Society of Anti-Infective Pharmacology.

Earlier ways of drug dosing and pharmacokinetic modeling emphasized enzyme metabolism, but did not adequately account for the movement of drugs and metabolites into and out of cells through molecular gatekeepers called transporters, Benet says. Benet was recognized for revising models to take transporters into account.

"You have to pay attention to the transporters," Benet says. "We're trying to understand how enzymes and transporters work together in the body."

For instance, Benet led research that showed why kidney failure must be taken into consideration, even when a drug normally is completely eliminated via the liver. "Uremic toxins can inhibit the transporters that are necessary to get drugs into the liver, and thus change how drug elimination occurs. These uremic toxins could also inhibit the ability of the drug to access its site of action in the body," he says.

In many cases, a metabolic enzyme and one or more drug transporters may work together as an inherent biological protective mechanism that prevents a drug (seen by the body as a xenobiotic) from reaching its site of action and functioning as a magic bullet, Benet suggests.