LESLIE Z. BENET, Ph.D., Professor of Biopharmaceutical Sciences and Pharmaceutical Chemistry

Dr. Benet and his research collaborators examine the disposition of drugs and their efficacious and toxic metabolites at the subcellular and cellular level, in isolated organs and in healthy volunteers and patients, so as to correlate the pharmacokinetics and pharmacodynamics of drugs in various patient populations. Specific study areas include:

1. The cooperative effects of metabolic isozymes of the cytochrome P450 and antitransport proteins as related to immunosuppressive, anti-cancer, anti-AIDS and anti-parasitic drugs, as well as drugs of importance to women’s health. Dr. Benet’s laboratory was the first to identify the strong overlap for substrates and inhibitors of cytochrome P450 3A isozymes (CYP3A) with substrates and inhibitors for the transporter P-glycoprotein.
2. Numerous drugs containing carboxylic acid functional groups which are metabolized via glucuronosyltransferases in humans by conjugation with glucuronic acid or through acyl CoA intermediates. Dr. Benet’s group has shown that acidic drugs can react with proteins and nucleic acids in vitro and in vivo forming covalent adducts which may lead to the immunologic toxicity of these drugs.

1. Benet LZ. There Are No Useful CYP3A Probes that Quantitatively Predict the In Vivo Kinetics of Other CYP3A Substrates and No Expectation that One Will Be Found. Mol Interv, 5(2):79-83, 2005.
2. Mohri K, Okada K, Benet LZ. Stereoselective taurine conjugation of (R)-benoxaprofen enantiomer in rats: in vivo and in vitro studies using rat hepatic mitochondria and microsomes. Pharm Res, 22(1):79-85, 2005.
3. Putnam WS, Woo JM, Huang Y, Benet LZ. Effect of the MDR1 C3435T Variant and P-Glycoprotein Induction on Dicloxacillin Pharmacokinetics. J Clin Pharmacol, 45(4):411-421, 2005.