Why patients respond differently to the same drug dose

Molecular Pharmaceutics

Why does the standard dose of certain medications prove dangerously high for some patients and too low to produce beneficial effects in others? Scientists have added a previously unrecognized factor to the list of explanations (such as age, gender, diet and genetics) for this common problem of individual variability in response to drugs.

Jeffrey P. Krise and Ryan S. Funk, at the University of Kansas, are reporting 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. Their study, which involved cultured human cells and a common anti-cancer drug, is scheduled for the Feb. 5, 2007, issue of the ACS's Molecular Pharmaceutics, a bi-monthly journal.

"The demonstrated correlation between hydrogen peroxide exposure and the concomitant increase in drug accumulation represents a substantial finding," the study reports. "The results suggest that patients experiencing oxidative stress (or an increase in hydrogen peroxide levels) may have an increased response to a given dosage of a drug relative to a patient with decreased oxidative stress, or those patients chronically taking antioxidants [such as vitamins C or E] with their medications. This could be a very important factor in our continued efforts to provide more individualized dosing of drugs."

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 very small changes in dosage level could cause either subtherapeutic or toxic results, they note.