William Elmquist

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William Elmquist, Pharm.D., Ph.D.

Academic Title

Department Head
Pharmaceutics

Professor

Director Brain Barrier Research Center

Education

Pharmacy School
Pharm.D. in Clinical Pharmacy, 1984
Bachelor's
B.S. in Pharmacy, 1982, University of Florida & B.A. in Zoology, 1976, University of South Florida
Ph.D.
Ph.D. in Pharmaceutics, 1992, University of Minnesota

Contact Info

Email
elmqu011@umn.edu

Phone
612- 625-0097

Fax
612- 626-2125

Office Address

Room 9-127D
Weaver-Densford Hall

Mailing Address

University of Minnesota
College of Pharmacy
Department of Pharmaceutics
Room 9-177 WDH
308 Harvard St. SE
Minneapolis, MN 55455
U.S.A.

Research Interests

Dr. Elmquist's laboratory studies the biochemical and physiological determinants of drug absorption, distribution and elimination. Most of this work has involved the use of in vitro cell culture and in vivo animal models. Recent studies have focused on the role of drug transport proteins in drug disposition. Particular emphasis has been placed on determining the role of membrane-associated drug transport proteins in the distribution of drugs to target tissues. Current research examines the effect that various drug transport systems, such as p-glycoprotein (ABCB1), the multidrug resistance-associated proteins (ABCCx), and the breast cancer resistance protein (ABCG2) have on drug distribution to the central nervous system (CNS). The use of molecular biology, in vitro models, intracerebral microdialysis and gene knockout animals have been important tools in this research.

An important project currently underway will examine the determinants of anticancer drug permeability in the blood-brain barrier. The effective treatment of many brain tumors is limited by inadequate delivery of the chemotherapy across the barriers of the CNS. Some of these compounds, specifically the molecularly targeted tyrosine kinase inhibitors, may be substrates for the drug efflux proteins found in these barriers and, as such, an opportunity to improve the targeted bioavailability to the CNS tumor may exist by inhibition of the efflux pump.

Long-term objectives of Dr. Elmquist's research include examining expression and regulation of transport systems in key tissues that influence drug disposition, and how variability in expression, either genetically or environmentally controlled, may contribute to variability in drug response in the patient.

Publications

Agarwal S., Sane R., Ohlfest J.R. and Elmquist W.F. Role of breast cancer resistance protein (ABCG2/BCRP) in the distribution of sorafenib to the brain. J. Pharmacol. Exp. Ther. Oct 15, 2010. [Epub ahead of print] PMID:20952483.

Agarwal S., Sane R., Gallardo J., Ohlfest J. and Elmquist W.F. Brain distribution of gefitinib is limited by p-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) mediated active efflux. J. Pharmacol. Exp. Ther. 334(1): 147-55 (2010).

Bungay P.M., Wang T., Yang H. and Elmquist W.F. Utilizing transmembrane convection to enhance solute sampling and delivery by microdialysis: theory and in vitro validation. Journal of Membrane Science 348(1-2): 131-149 (2010).

Pan G., Winter T.N., Roberts J.C., Fairbanks C.A. and Elmquist W.F. Organic cation uptake is enhanced in BCRP1-transfected MDCKII cells. Molecular Pharmaceutics 7(1): 138-145 (2010).

Chen Y., Agarwal S., Shaik N.M., Chen C., Yang Z. and Elmquist W.F. P-glycoprotein and breast cancer resistance protein influence brain distribution of dasatinib. J. Pharmacol. Exp. Ther. 330(3): 956-63 (2009).

Shaik N., Giri N. and Elmquist W.F. Investigation of the micellar effect of pluronic P85 on p-glycoprotein inhibition: cell accumulation and equilibrium dialysis studies. J. Pharm. Sci. 98(11): 4170-90 (2009).

Giri N., Agarwal S., Shaik N., Pan G., Chen Y. and Elmquist WF. Substrate-dependent breast cancer resistance protein (Bcrp1/Abcg2)-mediated interactions: consideration of multiple binding sites in in vitro assay design. Drug Metab Dispos. 37(3): 560-70 (2009).

Giri N., Pan G., Shaik N., Terasaki T., Mukai C., Kitagaki S., Miyakoshi N. and Elmquist W.F. Investigation of the role of Abcg2/Bcrp1 on pharmacokinetics and CNS penetration of abacavir (ABC) and aidovudine (AZT) in the mouse. Drug Metab. Dispos. 36(8): 1476-84 (2008).

Shaik N., Pan G. and Elmquist W.F. Interactions of pluronic block copolymers on P-gp efflux activity: experience with HIV-1 protease inhibitors. J. Pharm. Sci. 97(12): 5421-33 (2008).

Shaik N., Giri N., Pan G. and Elmquist W.F. P-glycoprotein-mediated active efflux of the anti-HIV1 nucleoside abacavir limits cellular accumulation and brain distribution. Drug Metabolism and Disposition 35(11): 2076-2085 (2007).

Pan G., Giri N. and Elmquist W.F. Abcg2/Bcrp1 mediates the polarized transport of anti-retroviral nucleosides abacavir and zidovudine. Drug Metabolism and Disposition 35(7): 1165-1173 (2007).

Pan G. and Elmquist W.F. Mitoxantone permeability in MDCKII cells is influenced by active influx transport. Molecular Pharmaceutics 4(3): 475-483 (2007).

Spitzenberger T.J., Heilman D., Diekmann C., Batrakova E., Kabanov A.V., Gendelman H.E., Elmquist W.F. and Persidsky Y. Novel delivery system enhances efficacy of antiretroviral therapy in animal model for HIV-1 encephalitis (HIVE). J. Cerebral Blood Flow and Metab. 27(5): 1033-1042 (2007).

Kirstein M.N., Brundage R.C., Elmquist W.F., Remmel R.P., Marker P.H., Guire D.E. and Yee D. Characterization of an in vitro cell culture bioreactor system to evaluate anti-neoplastic drug regimens. Breast Cancer Res. Treat. 96(3): 217-225 (2006).

Hitzman C.J., Elmquist W.F., Wattenberg L.W. and Wiedmann T.S. Development of a respirable, sustained release microcarrier for 5-fluorouracil I : In vitro assessment of liposomes, microspheres, and lipid coated nanoparticles. J. Pharm. Sci. 95(5): 1114-1126 (2006).

Hitzman C.J., Elmquist W.F. and Wiedmann T.J. Development of a respirable, sustained release microcarrier for 5-fluorouracil II : In vitro and in vivo optimization of lipid coated nanoparticles. J. Pharm. Sci. 95(5): 1127-1143 (2006).

Hitzman C.J., Wiedmann T.S., Dai H. and Elmquist W.F. Measurement of drug release from microcarriers by microdialysis. J. Pharm. Sci. 94(7): 1456-1466 (2005).

Bachmeier C.J., Spitzenberger T.J., Elmquist W.F. and Miller D.W. Quantitative Assessment of HIV-1 protease inhibitors interactions with drug efflux transporters in the blood brain barrier. Pharm. Res. 22(8): 1259-1268 (2005).

Dai H., Chen Y. and Elmquist W.F. Distribution of the novel antifolate Pemetrexed to the brain. J. Pharmacol. Exp. Therap. 315(1): 222-229 (2005).

Zhang Y., Schuetz J.D., Elmquist W.F. and Miller D.W. Plasma membrane localization of multidrug resistance-associated protein (MRP) homologues in brain capillary endothelial cells. J. Pharmacol. Exp Therap. 311(2): 449-455 (2004).

Benjamin R.K., Hochberg F.H., Fox E., Bungay P.M., Elmquist W.F., et al. Review of microdialysis in brain tumors, from concept to application: First Annual Carolyn Frye-Halloran Symposium. Neuro-Oncology 6(1): 65-74 (2004).

Dai H. and Elmquist W.F. Drug transport studies using quantitative microdialysis. Methods Mol. Med. 89: 249-264 (2003).

Sun H., Dai H., Shaik N. and Elmquist W.F. Drug efflux transporters in the CNS. Advanced Drug Delivery Reviews 55(1): 83-105 (2003).

Dai H., Marbach P., Lemaire M., Hayes M. and Elmquist W.F. Distribution of STI-571 to the brain is limited by p-glycoprotein mediated efflux. J. Pharmacol. Exp. Therap. 304(3): 1085-1092 (2003).

Dash A.K. and Elmquist W.F. Separation methods that are capable of revealing blood-brain barrier permeability. J. Chromatography B 797(1-2): 241-254 (2003).

Links

Department of Pharmaceutics

Brain Barriers Research Center

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  • Last modified on January 7, 2013