Research laboratory of Leslie Benet, PhD

Research & Projects

Research in the Benet Lab relates to the development of the correlation of pharmacokinetics and pharmacodynamics for drugs in various patient populations, with emphasis on the relevance of specific metabolic enzymes and drug transporters. We currently have three main lines of research.

Enzymes with efflux and uptake transporters as barriers

The Benet Lab was first to hypothesize and characterize the interplay between metabolic enzymes and drug transporters in the intestine and the liver. Early studies of this interplay in our lab include investigations of cytochrome P450 3A enzymes and P-glycoprotein as related to immunosuppressive, anti-cancer, anti-AIDS, and anti-parasitic drugs, as well as drugs of importance to women’s health. More recent work has concentrated on the interplay of hepatic enzymes with OATP uptake transporters and multiple hepatic efflux transporters for HMG CoA reductase inhibitors, macrolide antibiotics and antidiabetic drugs.

Development of the Biopharmaceutics Drug Disposition Classification System (BDDCS)

Proposed by Leslie Benet, PhD, in 2005, the Biopharmaceutics Drug Disposition Classification System (BDDCS) is a simple classification system that serves as a roadmap for predicting metabolic and transporter interactions for different classes of new molecular entities. Recent work has confirmed the hypotheses that Class 1, high soluble-highly permeable drugs, do not exhibit intestinal and liver transporter effects and that low permeability drugs are characterized by elimination from the body being primarily as unchanged drug in the bile and urine.

Carboxylic acid functional groups (R-COOH)

Numerous drugs containing carboxylic acid functional groups are metabolized in humans by conjugation with glucuronic acid and/or formation of acyl CoA intermediates. The Benet Lab continues to investigate whether acyl glucuronides and acyl CoA intermediates react with proteins and nucleic acids in vitro and in vivo forming covalent adducts and to define the mechanism of these reactions.