Leslie Z. Benet, Ph.D.
Professor of
Biopharmaceutical Sciences and Pharmaceutical Chemistry



Contact Information:
leslie.benet@ucsf.edu
Tel: (415) 476-3853
Fax: (415) 476-8887
U-68, Box 0446

Links:
Clinical Pharmacology

Publications

Development of the correlation of pharmacokinetics and pharmacodynamics, and the impact of pharmacogenetics, for drugs in various patient populations, with emphasis on the relevance of specific metabolic isozymes and drug transporters.

Study areas include:
(1) Dr. Benet has hypothesized that, in many cases, a metabolic enzyme and one or more drug transporters may work in concert as a protective mechanism. It is this interactive nature that confounds in vivo prediction of drug metabolism from in vitro microsomal studies. Studies are ongoing to examine the coordinated activity of Cytochrome P450 3A and glucuronacyltransferase enzymes with efflux (e.g., P-glycoprotein, MRP2) and uptake (e.g., OATP) transporters as barriers to drug availability and mediators of hepatic elimination, as related to immunosuppressives, anticancer, anti-aids, and anti-parasitic drugs;

(2) The development and characterization of immunologic measures for immunosuppressive activity and toxicity which can be correlated with the pharmacokinetics of immunoregulating agents and/or their metabolites, with particular emphasis on cyclosporine, tacrolimus, sirolimus and SDZ-RAD;

(3) Numerous drugs containing carboxylic acid functional groups are metabolized in humans by conjugation with glucuronic acid and/or formation of acyl CoA intermediates. Dr. Benet wishes to determine whether acyl glucuronides and acyl CoA intermediates react with proteins and nucleic acids in vitro and in vivo forming covalent adducts, and to describe the mechanism for these reactions. The stereoselective formation of metabolites, the covalent binding of nonsteroidal anti-inflammatory agents, and the immunologic consequence of this adduct formation are of particular interest;