Dr. Daniel S. Sitar
Daniel S. Sitar
Professor Emeritus
Department of Pharmacology and Therapeutics
University of Manitoba
Department of Internal Medicine (Clinical Pharmacology)
Department of Pediatrics and Child Health
College of Pharmacy
Centre on Aging
753 McDermot Avenue, Chown Building  A205, Winnipeg, MB R3E 0T6
Tel: 204-789-3532
Email: Daniel.Sitar@umanitoba.ca


Clinical Pharmacology at the University of Manitoba 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 was used formerly for influenza A prophylaxis, and currently 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 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 study area encompasses novel conjugation mechanisms in drug metabolism and their potential applications as diagnostic tools.  We have demonstrated that amantadine acetylation is mediated solely by spermidine/spermine N1-acetyltransferase (SSAT1).  The specificity of this metabolic reaction has implications for the diagnosis of cancer.  Worldwide patent applications have been filed, and our foundational findings are published.  A phase II clinical investigation to determine whether this metabolic reaction may be used for the diagnosis of cancer and/or assessment of the treatment response has been completed and supports our hypothesis.  We are now conducting phase III studies.  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, mass spectrometry 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.

 

Representative 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

Maksymiuk AW, Tappia PS, Sitar DS, Akhtar PS, Ahmed R, Ahmed RB, Cheng B, Huang G, Bach H, Hiebert B, Ramjiawan B (2018) Use of amantadine as substrate for SSAT-1 activity as a reliable clinical diagnostic assay for breast and lung cancer.  Future Sci OA. 2018 Dec 11;5(2):FSO365. doi: 10.4155/fsoa-2018-0106. eCollection 2019 Feb. PMID:30820345

 Maksymiuk AW, Sitar DS, Ahmed R, Cheng B, Bach H, Bagchi RA, Aroutiounova N, Tappia PS,Ramjiawan B (2018) Spermidine/Spermine N1-Acetyltransferase-1 (SSAT-1) as a Diagnostic Biomarker in Human Cancer. Future Sci OA. 2018 Sep 10;4(10):FSO345. doi: 10.4155/fsoa-2018-0077. eCollection 2018 Dec. PMID:30450232

 Sitar DS, Bowen JM, He J, Tesoro A, Spino M.  (2017)  Theophylline-7β-D-ribofuranoside (Theonosine), a new theophylline metabolite generated in human and animal lung tissue. Pharmaceutics 9(3), E28; doi: 10.3390/pharmaceutics9030028  PMID:28805720

 Head BM, Alfa M, Sitar DS, Rubinstein E, Meyers AFA.  (2017)  In vitro evaluation of the effect of linezolid and  levofloxacin on Bacillus anthracis toxin production, spore formation and cell growth.  J Antimicrob Chemother  72(2), 417-420. doi: 10.1093/jac/dkw427.  PMID:27798209

 Lillico R, Sayre CL, Sitar DS, Davies NM, Baron CM, Lakowski TM (2016) Quantification of cefazolin in serum and adipose tissue by ultra high performance liquid chromatography-Tandem mass spectrometry (UHPLC-MS/MS): application to a pilot study of obese women undergoing caesarean section delivery. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Jul 18;1031:94-98. doi:10.1016/j.jchromb.2016.07.032. PMID:27469905

 Sitar DS (2012) Clinical pharmacology confounders in older adults.  Expert Rev Clin Pharmacol  5(4), 397-402. PMID:22943119

 Ariano RE, Duke PC, Sitar DS (2012) The influence of sparse data sampling on population pharmacokinetics: a post-hoc analysis of a pharmacokinetics study of morphine in healthy volunteers.  Clin Ther 34(3), 668-676.  Epub ahead of print (Feb 28) doi:10.1016/j.clinthera.2012.01.023.  PMID:22381713

 Lehmann D, Sitar D (2011) The seduction of biomarkers in the practice of medicine and the tyranny of power in the drug approval process: lessons from niacin. J Clin Pharmacol 51(11), 1496-1498.  PMID:21998350

 Kozenko M, Grynspan D, Oluyomi T, Sitar D, Elliott AM, Chodirker BN  (2011) Potential teratogenic effects of allopurinol: a case report.  Am J Med Genet Part . A. 155(9), 2247-2252. (2011 Aug 3. doi: 10.1002/ajmg.a.34139. (Epub ahead of  print]). PMID:21815259

 Ariano RE, Sitar DS, Zelenitsky SA, Zarychanski R, Pisipati A, Ahern S, Kanji S,  McIntyre LL, Rello J, Kumar A (2010)   Enteric absorption and pharmacokinetics of oseltamivir in critically ill patients with pandemic (H1N1) influenza.  CMAJ 182(4), 357-363 ( Feb 2010; doi:10.1503/cmaj.092127).   PMID:20159892

 Gerlyand AM, Sitar DS (2009)  Protein kinase inhibition differentially regulates organic cation transport.  Can J Physiol Pharmacol 87(10), 821-830. PMID:20052008

 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). PMID:18495946

 Sitar DS (2007)  Adventures in drug disposition: pas seulement paté du foie.  Can J Physiol Pharmacol 85(12), 1215-1225. (Dec 7/07 ePub).  PMID:18066123

 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). PMID:17364191

 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). PMID:17141291

 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). PMID:16750190

 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. PMID:16641666

 Sitar DS (2005) Old drugs – Old people – New insights.  Can J Clin Pharmacol 12(1), e28-e32. (Jan 10/05, ePub).  PMID:15650276

 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). PMID:15126247

 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. PMID:15362593

 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.  PMID:14506511

 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. PMID:12515313

 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. PMID:12323380

 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. PMID:12438515

 Bras APM, Janne J, Porter CW, Sitar DS (2001) Spermidine/spermine N1-acetyltransferase catalyzes amantadine acetylation. Drug Metab Disposit 29(5), 676-68. PMID:11302933

 

 


Dr. Daniel S. Sitar
Area of research:  Clinical and renal pharmacology

In the news....

Department says good-bye to Head - Dr. Daniel S. Sitar
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