Friday, February 23, 2007
Researchers at KU discovered a factor in aging that could allow doctors to prescribe more appropriate drug doses in the future.
Jeffrey Krise, assistant professor of pharmaceutical chemistry and principle investigator of the study, said pharmacists in the past have noticed varying effects of drugs in patients of different ages, but no real answer had been discovered.
“I don’t think it’s fair to say that older people just complain a lot,” Krise said. “I think there’s really a reason behind it.”
After receiving a $1.5 million National Institutes of Health grant in 2004, Krise and Ryan Sol Funk, sixth year pharmacy student, started their study by breaking age difference into cell groups.
When any organism, from an apple to a human, ages, the organism’s cells gain oxygen molecules, becoming oxidized.
“When the sun bleaches something like a car, the color will become more dull,” Krise said. “That’s oxidation.”
To mimic aged cells, Krise and Funk exposed some cells to hydrogen peroxide, an oxidizing agent.
Then they exposed aged cells and cells in the control group to the same dose of therapeutic drug and examined the drug uptake.
The aged cells absorbed 100 times more of the drug than the control cells. This showed that the same dose given to an 18-year-old and a 68-year-old would have completely different effects.
Krise compared the cell membranes of the aged cells and the cells in the control group to a revolving door. If the door moved rapidly at one store and slowly at another, the same number of people would be able to get in the first store faster than the second store. This represents an older person’s cells being more responsive to the same amount of a drug than a younger person’s cells.
Most drug therapy is reactive, Krise said. All patients receive the same dose. If side effects occur, then the doctors may change the dose.
“That’s a really archaic way of going about this,” Krise said. “Right from the get-go, we should be giving the person the correct dosage.”
Although this study is a simple model, it could revolutionize drug therapy if proven in animal and human models, Funk said.
“If that big of a difference is seen in large-scale models, it will have a very big implication in clinical practice,” Funk said.
This research is specific to more than 20 therapeutic drugs that have a narrow therapeutic index, which means there is a fine line between a drug being therapeutic and toxic.
Cathy Thrasher, pharmacist supervisor at Watkins Memorial Health Center, said that Extra Strength Tylenol was one of those drugs. If a person exceeded more than 4,000 milligrams, or eight tablets, in a 24-hour period, it could cause serious adverse effects.
Kansan staff writer Danae DeShazer can be contacted at ddeshazer@kansan.com.
— Edited by Kelly Lanigan
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