Pharmacokinetics and Pharmacodynamics
Because of the MTDDP's strong emphasis on drug discovery and drug development, there is significant integration of activities involving pharmacokinetics, pharmacodynamics, and drug metabolism for a variety of antineoplastic agents, both in a preclinical setting and in clinical trials. This work is often performed in close collaboration with the UPCI Clinical Pharmacology Analytical Facility.
- Inositol hexaphosphate is effective in preclinical cancer prevention and chemotherapy. In addition to cancer, this compound has many other beneficial effects for human health, such as reduction in risk of developing cardiovascular disease and diabetes and inhibition of kidney stone formation. A pharmacokinetic study in mice found that after intravenous or oral administration, this compound was rapidly dephosphorylated to inositol (Eiseman J et. al. Metabolism. 2011 Oct;60(10):1465-74).
- Cytidine drugs, such as gemcitabine, undergo rapid catabolism and inactivation by cytidine deaminase (CD). 3,4,5,6-tetrahydrouridine (THU), a potent CD inhibitor, has been applied preclinically and clinically as a modulator of cytidine analogue metabolism. However, THU is only 20% orally bioavailable, which limits its preclinical evaluation and clinical use. Therefore, MTDDP investigators characterized THU pharmacokinetics after the administration to mice of the more lipophilic pro-drug triacetyl-THU (taTHU). The availability of THU after oral administration of taTHU is 30%, when compared to the 20% achieved with oral THU (Beumer JH et. al. Cancer Chemother Pharmacol 67:421-30, 2011).
|Beumer, Jan-Hendrik, PharmD, PhD
|Parker, Robert, PhD
Chemical & Petroleum Engineering
|Branch, Robert, MD, FRCP
|Potter, Douglas, PhD
|Eiseman, Julie, PhD
Pharmacology & Chemical Biology