Department of Medicinal Chemistry

Rory Remmel, Ph.D.

COP - Image - Size 3 - COP - Remmel Rory
    Medicinal Chemistry
  • B.S.
    University of Wyoming, 1976
  • B.S. Pharm
    University of Wyoming, 1977
  • Ph.D.
    University of Washington, 1982
  • 3-120 Weaver-Densford Hall
  • University of Minnesota
    College of Pharmacy
    Department of Medicinal Chemistry
    8-101 Weaver-Densford Hall
    308 Harvard St. SE
    Minneapolis, MN 55455

About Rory Remmel, Ph.D.

The primary focus in my laboratory is on drug metabolism and disposition. A major area of research involves studies on the mechanisms of metabolic interactions of antiepileptic drugs with a focus on drug interactions involving the UDP-glucuronosyltransferases and cytochrome P450 enzymes and glucuronidation Interactions between antiepileptic drugs such as phenytoin and cabamazepine and antidepressants are being examined with a bank of human liver microsomes from elderly donors. Stable isotope pharmacokinetic studies with phenytoin, carbamazepine, valproic acid, and lamotrigine have been conducted in elderly patients to understand the impact of aging and genetic polymorphisms on drug metabolism. Detailed enzyme kinetic studies with UGT1A4 and UGT1A1 are in progress. Studies on the regulation of UGTs are being done collaboratively in a transgenic mouse model in collaboration with Robert Tukey’s laboratory at UCSD. In order to identify and quantitate drugs and their metabolites in biological fluids, sophisticated analytical techniques such as HPLC, GC, CE, and mass spectrometry are developed in the laboratory.

Scientists with expertise in drug metabolism and pharmacokinetics are now part of early drug discovery in all major pharmaceutical companies. Collaborative projects are underway with the Ferguson lab (catalytic topoisomerase II inhibitors), the Aldrich laboratory (antituberculosis siderophores) and with Dr. Fecik’s laboratory at the University of Minnesota (CYP7B1 inhibitors) to optimize permeability, bioavailability, metabolic stability and tissue distribution in order to identify lead compounds that will have greater success in animal or clinical studies

Finally, a major collaborative initiative involves the development of a bioartificial liver that contains collagen-entrapped hepatocytes in a hollow-fiber reactor. Several approaches are being examined in an effort to maximize the biotransformation activity of the cultured pig cells (Nyberg lab, Mayo Clinic) or stem cells that can be transformed in into hepatocyte-like cells (Wei-Shou Hu laboratory) Optimization strategies include induction of P450 and UDP-glucuronosyltransferases, alteration of extracellular matrix, improving cell-cell contact by culturing hepatocytes into spheroidal aggregates, and targeted gene delivery to over-express key enzymes involved in detoxification of waste products and xenobiotics. The device has been successfully tested in animal models of liver failure. Systematic scale-up is underway in Dr. Scott Nyberg’s laboratory to test a device in patients with acute liver failure who are awaiting a liver transplant.

Published Works

Argikar UA, Remmel RP, Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UGT1A4, UGT1A8, and UGT1A10. Drug Metab. Disp. (in press).

Brophy CM, Luebke-Wheeler J, Amiot B, Remmel RP, Rinaldo P, Nyberg SL, Rat hepatocyte spheroids formed by a rocked technique maintain differentiated structure and function. Hepatology (in press).

Gupte A, Subramanian M, Remmel RP, Aldrich CC, Synthesis of Deuterium Labeled 5’-O-[N-(Salicyl)sulfamoyl]adenosine (Sal-AMS-d4) as an Internal Standard for Quantitation of Sal-AMS, J. Labeled Comp. Radiolab..(in press).

Johnson L, Baker KS, Orchard PJ, Remmel RP, Jacobson P. Glutathione-S-Transferase A1 genetic variants reduce busulfan clearance in children undergoing hematopoietic cell transplantation. J. Clin. Pharmacol. 48(9):1052-62 (2008).

Goodell JR, Ougolkov AV, Hiasa H, Kaur H, Remmel R, Billadeau DD, Ferguson DM. Acridine-based agents with topoisomerase II activity inhibit pancreatic cancer cell proliferation and induce apoptosis. J Med Chem. 51(2):179-82 (2008).

Subramanian M, Birnbaum AK, Remmel RP High Speed Simultaneous Determination of Nine Antiepileptic Drugs by Liquid Chromatography-Mass Spectrometry. Therap. Drug Monitor. 30:347-356 (2008).

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  • Last modified on October 30, 2014