Peter J. Harvison, PhD
 |
Peter J. Harvison, Ph.D.
BS (Carnegie-Mellon); PhD (SUNY, Buffalo)
Abramson Chair of Pharmacology
Research Associate Professor of Medicinal Chemistry
Associate Professor, Pharmaceutical Sciences
Email: p.harvis@usp.edu
Medicinal Chemistry
Biochemistry
PharmTox 237
215.596.8979
p.harvis@usp.edu
|
Research Interests
- Drug metabolism
- HPLC method development
- Structure activity/toxicity relationships
Research Summary
My research interests are primarily concerned with the effects of metabolism on the biological activity of chemicals (including drugs) to which humans and other mammals may be exposed. Although metabolism usually results in the formation of nontoxic substances, the opposite can also occur. For example, some chemicals are actually converted into highly toxic metabolites that can damage tissues or cause cancer.
In particular, my research has focused on a compound known as (3,5-dichlorophenyl)succinimide (NDPS), that was originally developed as an agricultural fungicide. Although NDPS is an effective antifungal agent, it is converted into metabolites that can produce severe kidney damage in laboratory rats. In fact, NDPS has never been used commercially due to concerns about its potential toxicity in humans. However, humans are exposed to compounds that are structurally related to NDPS. Therefore, a goal of my research efforts is to determine why NDPS is toxic. We use a variety of techniques, including high performance liquid chromatography (HPLC) and mass spectrometry, to investigate NDPS metabolism. These results of these studies may help us understand why NDPS and other chemicals can produce kidney damage in animals and humans.
Recent or Representative Publications
N.N. Patel, C.M. Crincoli, E.L. Kennedy, D.M. Frederick, R. Tchao and P.J. Harvison, Effect of gender, dose and time on 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione (DCPT)-induced hepatotoxicity in Fischer 344 rats”, Xenobiotica 38, 435-449 (2008).
C.M. Crincoli, N.N. Patel, R. Tchao and P.J. Harvison, “Role of biotransformation in 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione (DCPT)-induced hepatotoxicity in Fischer 344 rats”, Toxicology 250, 100-108 (2008).
D. Cui, G.O. Rankin and P.J. Harvison, “Metabolism of the nephrotoxicant N-(3,5-Dichlorophenyl)succinimide in rats: Evidence for bioactivation through alcohol-O-glucuronidation and O-sulfation”, Chem. Res. Toxicol. 18, 991-1103 (2005).
D. Cui, G.O. Rankin and P.J. Harvison, “Transamination in the metabolism of the nephrotoxicant N-(3,5-dichlorophenyl)succinimide in rats”, Drug Metab. Dispos. 33, 1765-1770 (2005).
E.L. Kennedy, R. Tchao and P.J. Harvison, “Nephrotoxic and hepatotoxic potential of imidazolidinedione-, oxazolidinedione-, and thiazolidinedione-containing analogues of N-(3,5-dichlorophenyl)succinimide (NDPS) in Fischer 344 rats”, Toxicology 186, 79-91 (2003).