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Ronald J. Sawchuk, Ph.D. Professor, Department of Pharmaceutics E-mail: sawch001@umn.edu

Research Interests:

A major focus of my laboratory's research is in neuropharmaceutics and in the delivery of drugs to the central nervous system. One goal of this work is to enhance the distribution of centrally acting agents to the brain. Ongoing research involves the targeting of antiviral compounds to brain tissue in an effort to optimize the delivery of drugs used in treating HIV encephalopathy. An area of emphasis here is the use of transport inhibitors to alter the distribution of such agents across the blood-brain barrier. Similar studies are also being undertaken to examine factors that affect access of other centrally acting drugs to the brain. Of interest is the mode of access of very hydrophilic agents, such as phosphate-containing NMDA antagonists, and the importance of tissue penetration of drugs from cerebrospinal fluid.

These investigations employ microdialysis in freely moving/conscious animals to continuously monitor the concentration of the drug and/or its metabolites in tissue extracellular space. Microdialysis is coupled online to high-pressure liquid chromatography, where possible, to determine analyte concentrations in the CNS in real time. We have utilized models which consider spatially-distributed concentrations of these agents in brain extracellular fluid. Other neuropharmacokinetic models have been developed to determine the relative advantage in tissue distribution realized by delivering water-soluble centrally acting agents via the intracerebroventricular route.

Selected Publications:

(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)

Huang Y, Yang Z, Cartier L, Cheung B, Sawchuk RJ. Estimating amoxicillin influx/efflux in chinchilla middle ear fluid and simultaneous measurement of antibacterial effect. Antimicrob Agents Chemother. 2007 Dec;51(12):4336-41.

Karjagin J, Lefeuvre S, Oselin K, Kipper K, Marchand S, Tikkerberi A, Starkopf J, Couet W, Sawchuk RJ. Pharmacokinetics of Meropenem Determined by Microdialysis in the Peritoneal Fluid of Patients With Severe Peritonitis Associated With Septic Shock. Clin Pharmacol Ther. 2007 Aug 8.

Chaurasia CS, Müller M, Bashaw ED, Benfeldt E, Bolinder J, Bullock R, Bungay PM, DeLange EC, Derendorf H, Elmquist WF, Hammarlund-Udenaes M, Joukhadar C, Kellogg DL Jr, Lunte CE, Nordstrom CH, Rollema H, Sawchuk RJ, Cheung BW, Shah VP, Stahle L, Ungerstedt U, Welty DF, Yeo H. AAPS-FDA workshop white paper: microdialysis principles, application and regulatory perspectives. Pharm Res. 2007 May;24(5):1014-25.

Chaurasia CS, Müller M, Bashaw ED, Benfeldt E, Bolinder J, Bullock R, Bungay PM, DeLange EC, Derendorf H, Elmquist WF, Hammarlund-Udenaes M, Joukhadar C, Kellogg DL Jr, Lunte CE, Nordstrom CH, Rollema H, Sawchuk RJ, Cheung BW, Shah VP, Stahle L, Ungerstedt U, Welty DF, Yeo H. AAPS-FDA Workshop White Paper: microdialysis principles, application, and regulatory perspectives. J Clin Pharmacol. 2007 May;47(5):589-603.

Yang Z, Gan G, Sawchuk RJ. Correlation between net water flux and absorptive clearance determined from in situ intestinal perfusion studies does not necessarily indicate a solvent drag effect. J Pharm Sci. 2007 Mar;96(3):517-21.

Yang Z, Manitpisitkul P, Sawchuk RJ. In situ studies of regional absorption of lobucavir and ganciclovir from rabbit intestine and predictions of dose-limited absorption and associated variability in humans. J Pharm Sci. 2006 Oct;95(10):2276-92.

Recent Graduate Students:

Yanfeng Wang (Ph.D., Pharmaceutics, 1994) Research Scientist, Merck and Company

Bimal Malhotra (Ph.D., Pharmaceutics, 1994) Research Scientist, Bristol-Myers Squibb, Princeton NJ

Richard Brundage (Ph.D., Pharmaceutics, 1996) Research Associate, University of Minnesota. Minneapolis MN

Zheng Yang (Ph.D., Pharmaceutics, 1997) Research Investigator, Bristol-Myers Squibb, Wallingford CT

Belinda Cheung (Ph.D., Pharmaceutics, 1998) Research Associate, Assistant Professor, University of Minnesota. Minneapolis MN