Daniel S. Sitar, BScPharm, MSc, PhD, FCP
Professor, Department of Pharmacology and Therapeutics
Professor, Department of Internal Medicine (Clinical Pharmacology Section)
Professor, Department of Pediatrics and Child Health
Professor, Faculty of Pharmacy
Research Affiliate, Centre on Aging
University of Manitoba
753 McDermot Avenue,  Chown Building A220,
Winnipeg, MB R3E 0T6
tel: (204) 789-3532 fax: (204) 789-3932 email: sitar@cc.umanitoba.ca

Summary of Research:   The Clinical Pharmacology Section has a long-term interest in issues related to optimization of drug therapy of chronic diseases, especially in elderly patients. My own research focus relates to mechanisms of drug disposition, and their alteration as a result of development and disease processes.  One study area includes control mechanisms governing renal excretion of basic drugs. The prototypical model substrate for these studies is amantadine, which is used for influenza A prophylaxis and in the management of Parkinson's disease. Both in vivo studies in animal models and humans and in vitro studies with animal and human kidney tissue are being used in order to determine pathologically relevant situations in which renal tubular transport is altered. One focus is on the effects of early diabetes on renal tubular organic cation transport.  Another research area encompasses novel conjugation mechanisms in drug metabolism and their potential applications as diagnostic tools.  We have recently demonstrated that amantadine acetylation is mediated solely by spermidine/spermine N¹-acetyltransferase.  The specificity of this metabolic reaction has implications for the diagnosis of cancer.  World-wide patent applications have been filed, and our foundational findings are published.  A phase II clinical investigation to determine whether this metabolic reaction can be used for the diagnosis of cancer and/or assessment of the treatment response has been recently completed and supports our hypothesis.  In addition, our laboratory is involved in collaborative research related to the discovery of new therapeutic targets, and the optimization of drug therapy. Many of these studies are using pharmacokinetic and pharmacodynamic modeling as investigative tools to determine the potential for drug dose modification in relevant patient populations. All of these research projects involve analytical methods by high performance liquid chromatography, gas liquid chromatography and radioactive isotope tracer techniques. Data analyses include pharmacokinetic modelling and classic enzyme kinetic approaches.  Finally, we continue our studies in clinical toxicology that are directed at evaluating candidate regimens for their potential efficacy in gastrointestinal tract decontamination.  As of January 1, 2009, Dr. Sitar is the Editor-in-Chief of the Journal of Clinical Pharmacology, the official journal of the American College of Clinical Pharmacology.

Dept. of Pharmacology & Therapeutics - Decennial Report  (1999 - 2008)
Prepared by:   Daniel S. Sitar, BScPharm, MSc, PhD, FCP
view online:  http://myuminfo.umanitoba.ca/index.asp?sec=900&too=100&eve=501&id=19229&_wor=1

Representative Recent Publications

For a more comprehensive list of publications by Dr. D. Sitar, please go to the following website:        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed

            and type:   sitar d*           as the search term

Sitar DS, Aoki FY, Bow EJ (2008)  Acyclovir bioavailability in patients with acute myelogenous leukemia treated with daunorubicin and cytarabine.  J Clin Pharmacol 48(8), 995-998. (May 21, Epub ahead of print – doi:10.1177/0091270008319708).

Sitar DS (2007)  Adventures in drug disposition: pas seulement paté du foie.  Can J Physiol Pharmacol 85(12), 1215-1225. (Dec 7/07 ePub).

Sammons HM, Malhotra J, Choonara I, Sitar DS, Matsui D, Rieder MJ (2007) British and Canadian views on the ethics of paediatric research.  Eur J Clin Pharmacol 63(5), 431-436.  (Mar 16/07 ePub).

Hussein J, Farkas S, McKinnon Y, Ariano RE, Sitar DS, Hasan SU (2007) Nicotine dose-concentration relationship and pregnancy outcomes in rat : biologic plausibility and implications for future research.  Toxicol Appl Pharmacol 218(1), 1-10.  (Oct 28/06, ePub).

Goralski KB, Bose R, Sitar DS (2006) NH₄⁺ modulates renal tubule amantadine transport independently of  intracellular pH changes.  Eur J Pharmacol 541(1 + 2), 87-94. (May 7/06, ePub).

Grymonpre RE, Cheang M, Fraser M, Metge C, Sitar DS (2006) Validity of a prescription claims database to estimate medication adherence in older persons.  Med Care 44(5), 471-477.

Sitar DS (2005) Old drugs – Old people – New insights.  Can J Clin Pharmacol 12(1), e28-e32. (Jan 10/05, ePub).

Wright SH, Evans KK, Zhang Z, Cherrington NJ, Sitar DS, Dantzler WH (2004) Functional map of TEA transport activity in isolated rabbit renal proximal tubules.  Am J Physiol Renal Physiol 287(3), F442-F451.  (May 4/04, ePub).

Green R, Sitar DS, Tenenbein M (2004) Effect of anticholinergic drugs on the efficacy of activated charcoal. J Toxicol Clin Toxicol 42(3), 267-272.

Kolbe F, Sitar DS, Papaioannou A, Campbell G (2003) An amantadine dosing program adjusted for renal function during an influenza outbreak in elderly institutionalized patients. Can J Clin Pharmacol 10(3), 119-122.

Garnham BM, Fitzpatrick-Wong S., Schunack W, Nürnberg B, Sorrentino G, Parkinson FE, Kanfer JN, Sitar DS (2002) Activation of phospholipases A₂ and D of a human neuroblastoma cell line (LA-N-2) by N-dodecyl-L-lysine amide (compound 24), a putative G protein activator: characteristics of inhibition by (-)-nicotine.  Neurochem Res 24(12), 1621-1630.

Fourie J, Escobar MR, Sitar DS (2002) NMDA receptor antagonists to characterize rat renal organic cation transporter function.  Eur J Pharmacol 452(1), 1-10.

Goralski KB, Lou G, Prowse MT, Gorboulev V, Volk C, Koepsell H, Sitar DS (2002)  The cation transporters rOCT1 and rOCT2 interact with bicarbonate but play only a minor role for amantadine uptake into rat renal proximal tubules.  J Pharmacol Exp Ther 303(3), 959-968.

Bras APM, Janne J, Porter CW, Sitar DS (2001) Spermidine/spermine N¹-acetyltransferase catalyzes amantadine acetylation. Drug Metab Disposit 29(5), 676-680.

Ariano RE, Duke PC, Sitar DS (2001) Population pharmacokinetics of fentanyl in healthy volunteers.  J Clin Pharmacol 41, 757-763.

Green R, Grierson R, Sitar DS, Tenenbein M (2001) How long after drug ingestion is activated charcoal still effective? J Toxicol Clin Toxicol 39(6), 601-605.

In the news....

Department says good-bye to Head - Dr. Daniel S. Sitar
http://myuminfo.umanitoba.ca/index.asp?sec=900&too=100&eve=1000&id=18192

Dr. Daniel Sitar receives Pharmacology Society Senior Investigator Award
http://myuminfo.umanitoba.ca/index.asp?sec=900&too=100&eve=1000&id=12473

Dr. Daniel Sitar Editor Designate for Journal of Clinical Pharmacology
http://myuminfo.umanitoba.ca/index.asp?sec=40&too=100&eve=1000&id=15583

Researcher discovers nicotine protects against Alzheimer's
http://myuminfo.umanitoba.ca/index.asp?sec=7&too=100&eve=1000&id=2613

Sitar receives Senior Investigator Award
http://myuminfo.umanitoba.ca/index.asp?sec=40&too=100&eve=1000&id=12789

Does smoking protect the brain from alzheimer's disease?
http://myuminfo.umanitoba.ca/index.asp?sec=209&too=100&eve=1000&id=2547