Drug-interaction research a challenge with herbal products

By Lorraine Nelson, College of Pharmacy

Paine-80SPOKANE, Wash. – The cover story of the news magazine published in April by the American Association of Pharmaceutical Scientists came from Mary Paine’s research lab at the Washington State University College of Pharmacy.

The lead author of the five-page article is Brandon Gufford, a Ph.D. student in Paine’s lab.

“I am interested in interactions between dietary and herbal substances and conventional medications,” Paine said. “How can these substances alter blood concentrations of drugs?

“We know grapefruit juice inhibits the metabolism of certain drugs,” she said. “Could any of these other substances inhibit the metabolism – or some other elimination process – of a drug and cause unwanted effects?”

cover-story-600Paine is senior author on the article, which discusses the challenges of studying herbal products – one of which is the different growing conditions and manufacturing processes of the products that lead to large variations in biochemical makeup. Unlike most drug products, one brand is not predictive of all brands.

“The scary thing about these products is they are not regulated like drugs,” Paine said. “Manufacturers don’t have to prove efficacy or safety.”

Clinical trial starting in June

The article steers readers through the three-pronged testing approach used in Paine’s lab: in vitro (petri dish or test tube), in silico (computer modeling) and in vivo (inside a living organism).

For the in vivo, Paine uses healthy human subjects. She has plans for a small clinical trial in June, her first since moving to Spokane almost a year ago from the University of North Carolina at Chapel Hill.

Paine became interested in this line of research while doing a postdoctoral fellowship at the University of Michigan, where she went primarily to learn a particular cell culture model in the laboratory of Paul Watkins.

He was one of the pioneers in the grapefruit juice research, and when he relocated two years later to direct the clinical research center at UNC Chapel Hill, he asked Paine to move his research lab there. She did, after which she managed the lab for about five years.

Watkins decided to shift his research to drug-induced liver injury, opening the door for her to pursue further the grapefruit juice research and expand to other natural products.

By then she had discovered a love of everything about clinical research, from interacting with the subjects and professional colleagues to analyzing the data collected. It reminded her of the three years she worked as a hospital pharmacist in Portland, Ore., between graduating from pharmacy school at Oregon State University and pursuing a Ph.D. in pharmaceutics at the University of Washington.

When Watkins shifted direction, Paine got her own grant funding and lab and became an assistant professor at UNC. She was doing that when former UNC colleague Gary Pollack recruited her to the WSU College of Pharmacy, where he serves as dean.

Research lab moved from North Carolina

In addition to grapefruit juice, Paine’s lab is studying the popular herbal product milk thistle. Three of her lab members – two Ph.D. students and a postdoctoral fellow on faculty in the college – moved with her from North Carolina to Spokane. She has since attracted another postdoc as well as a doctor of pharmacy honors student just finishing her first year of the program.

Mary Paine and her research lab pose for a photo in front of the Pharmaceutical and Biomedical Sciences building. From left to right are postdoctoral student John Barr, doctor of pharmacy honors student Hope Tran, assistant research professor Vanessa Gonzalez-Perez, doctoral student Brandon Gufford, associate professor Mary Paine and research associate Garrett Ainslie. All but Barr and Tran moved with Paine from North Carolina to Spokane.

Interacting with these talented people is what Paine enjoys most about her job, although she is looking forward to the clinical trial.

She was in high school when she decided to go into pharmacy, although she cannot explain why. She was sitting on a hill on her family’s Christmas tree farm outside of Corvallis, Ore., where her father was a professor of forestry at OSU, pondering the question, “What do I want to do . . . I like chemistry and math.”

Out of the blue, “pharmacy” popped into her head. She tried out the idea on her parents and they liked it, so she followed it. Many of her other life’s decisions were made the same way.

“I think if you plan too much for the future you miss out on unforeseen opportunities,” Paine said.

When she was recruited to leave North Carolina for Spokane, she kept thinking that she was doing “fine, just fine” in North Carolina but maybe a new challenge would be good, especially one where she could be a part of building up the College of Pharmacy after it relocated from Pullman to Spokane.

“I miss the South and being surrounded by research-intensive institutions, but it’s exciting to be a part of what is happening in this college,” she said.