KU News Release

KU professor, student find new variable in common drug therapy problem

LAWRENCE — A University of Kansas researcher and a pharmacy student from Newton have uncovered a potentially important variable to aid in understanding a common problem in drug therapy: why a standard dosage may not work for all patients.

Jeffrey P. Krise, assistant professor of pharmaceutical chemistry and the principle investigator for the study, together with Ryan S. Funk, in his sixth year of KU’s doctor of pharmacy program, published their study in the Feb. 5 issue of Molecular Pharmaceutics, a bi-monthly journal of the American Chemical Society.

Their findings may help scientists better understand why a standard dose of certain medications prove dangerously high for some patients and too low to produce beneficial effects in others. Previously, scientists recognized factors such as age, gender, diet and genetics as contributing to the variable responses to standard dosages.

The study, which involved cultured human cells and a common anti-cancer drug, found that variations in the body’s production of hydrogen peroxide — believed to serve as a signaling molecule at low levels — can affect accumulation of drugs inside cells.

Hydrogen peroxide’s effects could be especially important in about two dozen so-called narrow therapeutic index drugs (such as aminophylline, carbamazepine, lithium carbonate, phenytoin, theophylline and warfarin) for which small changes in dosage level could result in no beneficial effect or be toxic, they note.

The study was funded through a five-year National Institutes of Health grant made to Krise in 2004 for his work aimed at evaluating factors that influence drug accumulation and distribution within human cells.

Though Krise regularly works with graduate students in his lab, he recognized Funk as a talented and promising senior in KU’s professional pharmacy degree program and offered him an opportunity to participate in the study.

“Ryan is a very bright and talented student currently finishing up his degree in the School of Pharmacy,” said Krise. “Considering his abilities and his interest in research, I gave him his own independent project.”

The drug response study, titled “Exposure of Cells to Hydrogen Peroxide Can Increase the Intracellular Accumulation of Drugs,” is the first in which Funk is listed as a primary author of a published journal article. Funk has also been listed among contributing authors for an article published in the journal Biochemistry. Following his graduation this May, Funk hopes to continue his education in the pharmaceutical sciences. His long-term goal is to work with a team of scientists in the pharmaceutical industry. He is a Newton High School graduate and the son of Elmer and Christine Funk, Newton.

The American Chemical Society — the world’s largest scientific society — is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.

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