Mary F. Paine, Ph.D.

Education
Ph.D. in pharmaceutics, University of Washington
Bachelor of Science in pharmacy, Oregon State University

Licensure
Registered Pharmacist

Fellowships
Postdoctoral fellowship at the University of Michigan Medical Center

Research
The Paine Lab is applying a translational research approach that encompasses human-derived in vitro systems, mathematical modeling, and proof-of-concept clinical studies to advance the mechanistic understanding of pharmacokinetic interactions between conventional medications and diet-derived substances, including herbal products and exotic beverages. Results will help to provide evidenced-based recommendations to health care providers and consumers about the risk of supplementing prescribed drug therapies with certain diet-derived substances.

Current Research Support
• Research Grant - Supplement for Collaborative Sciences: 3R01 GM077382-7S1
Sponsor: NIGMS, NIH
Title: Mechanisms Underlying Drug-Diet Interactions - Administrative Supplement
Role: Principal Investigator
Period: July 2013 - August 2015
This supplement expands upon the aims of the parent R01 grant by examining potential clinically relevant UGT-mediated interactions between diet-derived constituents and conventional medications.

• Elmer M. Plein Endowed Research Grant
Sponsor: University of Washington School of Pharmacy
Title: Effects of Therapeutic Hypothermia on Prasugrel Pharmacokinetics
Role: Principal Investigator
Period: March 2013 - August 2014
The goal of this pilot study is to evaluate the effects of therapeutic hypothermia on the absorption of the prodrug prasugrel and formation of the active drug. Funds will be used to develop a bioanalytical (LC-MS/MS) method for quantitation of active drug in plasma.

• Pilot Grant
Sponsor: NC TraCS Institute, UNC
Title: Effects of Therapeutic Hypothermia on Prasugrel Pharmacokinetics
Role: Co-Investigator (Elizabeth Blair, Principal Investigator)
Period: November 2012 - October 2014
The goal of this pilot study is to evaluate the effects of therapeutic hypothermia on the absorption of the prodrug prasugrel and formation of the active drug. Funds will be used to acquire analytical standards needed for bioanalytical method development.

• Research Grant: 7R01 GM077482-07
Sponsor: NIGMS, NIH
Title: Mechanisms Underlying Drug-Diet Interactions
Role: Principal Investigator
Period: August 2011 - July 2015
The long-term goal of this translational research program is to develop rigorous guidelines to evaluate, prospectively, potential drug-dietary substance interactions. An established partnership between pharmacokineticists and natural products chemists will use an integrative in vitro-in silico-in vivo approach to identify specific compounds and to elucidate mechanisms underlying clinically relevant drug-dietary substance interactions.

Additional Information
Dr. Mary Paine joined the WSU College of Pharmacy in 2013. She had been an assistant professor at the University of North Carolina at Chapel Hill. Paine is a registered pharmacist who practiced for four years as a hospital pharmacist after completing her bachelor’s in pharmacy and before returning to school to pursue her Ph.D. She completed a postdoctoral fellowship at the University of Michigan Medical Center studying various enzymes in the digestive process that effect the absorption, distribution and metabolism of drugs. In 1999, she joined UNC to lead a translational research laboratory in the General Clinical Research Center. She later became an assistant professor at the Eshelman School of Pharmacy.

Selected Publications
VanderMolen KM, Ainslie GR, Paine MF, Oberlies NH. Labeled content of two furanocoumarins in dietary supplements correlates with neither actual content nor CYP3A inhibitory activity. J Pharmaceut Biomed Anal, accepted for publication. PMCID: pending.

Brantley SJ, Gufford BT, Dua R, Fediuk DJ, Graf TN, Scarlett YV, Frederick KS, Fisher MB, Oberlies NH, Paine MF. Physiologically-based pharmacokinetic modeling framework for quantitative prediction of an herb-drug interaction. CPT Pharmacometrics Syst Pharmacol 3:e107, 2014. PMCID: pending.

Brantley SJ, Argikar AA, Lin YS, Nagar S, Paine MF. Herb-drug interactions: challenges and opportunities for improved predictions. Drug Metab Dispos 42:301-17, 2014. PMCID: PMC3935140.

Brantley SJ, Graf TN, Oberlies NH, Paine MF. A systematic approach to evaluate herb-drug interaction mechanisms: investigation of milk thistle extracts and eight isolated constituents as CYP3A inhibitors. Drug Metab Dispos 41:1662-70, 2013. PMCID: PMC3876807.

Won CS, Lan T, Vandermolen KM, Dawson PA, Oberlies NH, Widmer WW, Scarlett YV, Paine MF. A modified grapefruit juice eliminates two compound classes as major mediators of the grapefruit juice-fexofenadine interaction: an in vitro-in vivo "connect". J Clin Pharmacol 53:982-90, 2013. PMCID: PMC4029847.

Thuita JK, Wolf KK, Murilla GA, Liu Q, Mutuku JN, Chen Y, Bridges AS, Mdachi RE, Ismail MA, Ching S, Boykin DW, Hall JE, Tidwell RR, Paine MF, Brun R, Wang MZ. Safety, pharmacokinetic, and efficacy studies of oral DB868 in a first stage vervet monkey model of human African trypanosomiasis. PLoS Negl Trop Dis 7:e2230, 2013.

VanderMolen KM, Cech NB, Paine MF, Oberlies NH. Rapid quantitation of furanocoumarins and flavonoids in grapefruit juice using ultra performance liquid chromatography Phytochem Anal 24:654-60, 2013. PMCID: PMC3855432.

Althagafy HS, Graf TN, Sy-Cordero AA, Gufford BT, Paine MF, Wagoner J, Polyak SJ, Croatt MP, Oberlies NH. Semisynthesis, cytotoxicity, antiviral activity, and drug interaction liability of 7-O-methylated analogues of flavonolignans from milk thistle Bioorg Med Chem 21:3919-26, 2013. PMCID: PMC3855444.

Sy-Cordero AA, Graf TN, Runyon SP, Wani MC, Kroll DJ, Agarwal R, Brantley SJ, Paine MF, Polyak SJ, Oberlies NH. Enhanced bioactivity of silybin B methylation products. Bioorg Med Chem 21:742-7, 2013. PMCID: PMC3630461.

Generaux CN, Ainslie GR, Bridges AS, Ismail MA, Boykin DW, Tidwell RR, Thakker DR, Paine MF. Compartmental and enzyme kinetic modeling to elucidate the biotransformation pathway of a centrally acting antitrypanosomal prodrug. Drug Metab Dispos, 41:518-28, 2013.

Harrill AH, Desmet KD, Wolf KK, Bridges AS, Eaddy JS, Kurtz CL, Hall JE, Paine MF, Tidwell RR, Watkins PB. A mouse diversity panel approach reveals the potential for clinical kidney injury due to DB289 not predicted by classical rodent models. Toxicol Sci 130:416-26, 2012. PMCID: PMC3498743.

González-Pérez V, Connolly EA, Bridges AS, Wienkers LC, Paine MF. Impact of organic solvents on cytochrome P450 probe reactions: filling the gap with (S)-warfarin and midazolam hydroxylation. Drug Metab Dispos 40:2136-42, 2012. PMCID: PMC3477202.

Thuita JK, Wang MZ, Kagira JM, Denton CL, Paine MF, Mdachi RE, Murilla GA, Ching S, Boykin DW, Tidwell RR, Hall JE, Brun R. Pharmacology of DB844, an orally active aza analogue of pafuramidine, in a monkey model of second stage human African trypanosomiasis. PLoS Negl Trop Dis 6:e1734, 2012.

Yang J, Atkins WM, Isoherranen N, Paine MF, Thummel KE. Evidence of CYP3A allosterism in vivo: analysis of interaction between fluconazole and midazolam. Clin Pharmacol Ther 91:442-9, 2012. PMCID: PMC3830930.

Yan GZ, Generaux CN, Yoon M, Goldsmith RB, Tidwell RR, Hall JE, Olson CA, Clewell HJ, Brouwer KLR, Paine MF. A semi-physiologically-based pharmacokinetic modeling approach to predict the dose-exposure relationship of an antiparasitic prodrug/active metabolite pair. Drug Metab Dispos 40:6-17, 2012. PMCID: PMC3250045.

Yan GZ, Brouwer KLR, Pollack GM, Wang MZ, Tidwell RR, Hall JE, Paine MF. Mechanisms underlying differences in systemic exposure of structurally similar active metabolites: comparison of two preclinical hepatic models. J Pharmacol Exp Ther 337:503-12, 2011. PMCID: PMC3083101.

Kim E, Sy-Cordero A, Graf TN, Brantley SJ, Paine MF, Oberlies NH. Isolation and identification of intestinal CYP3A inhibitors from cranberry (Vaccinium macrocarpon) using human intestinal microsomes. Planta Med, 77:265-70, 2011. PMCID: PMC3023844.

Paine MF, Wang MZ, Generaux CN, Boykin DW, Wilson WD, De Koning HP, Olson CA, Pohlig G, Burri C, Brun R, Murilla GA, Thuita JK, Barrett MP, Tidwell RR. Diamidines for human African trypanosomiasis. Curr Opin Investig Drugs 11:876-83, 2010.

Ngo N, Brantley SJ, Carrizosa DR, Kashuba AD, Dees EC, Kroll DJ, Oberlies NH, Paine MF. The warfarin-cranberry juice interaction revisited: a systematic in vitro-in vivo evaluation involving multiple cranberry juice products. J Exp Pharmacol 283-91, 2010.

Brantley SJ, Oberlies NH, Kroll DJ, Paine MF. Two flavonolignans from milk thistle (Silybum marianum) inhibit CYP2C9-mediated warfarin metabolism at clinically achievable concentrations. J Pharmacol Exp Ther 332:1081-7, 2010.

Recent Invited Presentations
AAPS Rocky Mountain Discussion Group, Missoula, MN, August 14, 2014. Title TBD.

GlaxoSmithKline, Shanghai, China, May 15, 2014. Predicting dietary substance-drug interactions using an IVIVE approach.

Shanghai Institute of Materia Medica, Shanghai, China, May 14, 2014. Quantitative prediction of dietary substance-drug interactions: challenges and opportunities.

5th Asia Pacific ISSX Meeting – Symposium: Herb-Drug Interactions, Tianjin, China, May 11, 2014. Predicting herb-drug interactions via an integrated in vitro-in silico-in vivo approach.

Janssen Pharmaceuticals BIDS-4 meeting, Lambertville, NJ, September 26, 2012. Pharmacokinetic modeling and simulation in the Paine research group. (In Conjunction with Drs. Dhiren Thakker and Kim Brouwer)

Department of Pharmacology Seminar Series, Emory University, Atlanta, GA, September 11, 2012. Fruit juice-drug interactions: mechanisms and causative ingredients.

Gordon Research Conference, Plymouth, NH, July 10, 2012. Predicting interactions between drugs and dietary substances by IVIVE.

Recent Invited Book Chapters
Paine MF. Gut Wall Metabolism. In: Oral Drug Absorption – Prediction and Assessment. Dressman JB, Reppas C (eds.). Informa Healthcare USA, Inc., New York, NY, 2010, pp. 66-89.

Wolf KK, Watkins PB, Paine MF. Metabolic Barrier of the Gastrointestinal Tract. In: Gastrointestinal Toxicology, Volume 10 of Comprehensive Toxicology (2nd ed). Hooser S (volume ed.). Elselvier Ltd, Kidlington, UK, 2010, pp. 54-75.

Wolf KK, Gufford BT, Brantley SJ, Watkins PB, Paine MF. Drug Metabolism, Transport, and Pharmacogenomics. In: Yamada’s Textbook of Gastroenterology, 6th Edition. Shanahan F (ed.). Wiley-Blackwell, West Sussex, UK, in press.

updated 06/08/2015   back to top
photo of Dr. Mary Paine

Associate Professor
Pharmaceutical Sciences

 

Paine Lab website »

 

mary.paine@wsu.edu
509-358-7759

Office: PBS 341
P.O. Box 1495
Washington State University
Spokane, WA 99210-1495