OHSU researchers test medication that targets fever without side effects

September 22, 1999

September 21, 1999, Portland, Ore.--Each year, cold and flu season closely follows the beginning of the school year. But for some of those who become ill, drugs that fight high fever can also wage a war in other organs in the body. Many common fever reducers like ibuprofen can agitate ulcers, cause upset stomachs and trigger kidney problems in some patients. Now, thanks in part to research at Oregon Health Sciences University, drugs that avoid some of the common side effects of other cold and flu treatments may soon be on the market.

OHSU was one of the sites involved in a multi-state clinical trial of the drug rofecoxib. The testing showed that the drug reduced fever without appearing to affect other important body functions.

To come to this conclusion, patients with fever were solicited through advertisements. Some subjects were given the drug rofecoxib, other patients received ibuprofen and yet another group was given a placebo. Researchers found that all the patients treated with ibuprofen and rofecoxib witnessed a similar drop in fever, despite the fact that the drugs work in very different ways.

Most fever reducers currently on the market target cyclooxygenase (COX) enzymes. Two different forms of the enzyme exist in the body. COX-1 is found in many tissues such as the stomach and the kidneys, where it is involved with day-to-day bodily functions. In contrast, the COX-2 enzyme is not found in most tissues, but surfaces in response to illness. While most medications like ibuprofen affect both forms of the enzyme, rofecoxib specifically targets COX-2. That means COX-1 is left to support normal functions in the body while the new drug inhibits fever production by the COX-2 enzyme. In the past, the interruptions of COX-1 functions have been known to cause kidney and stomach problems for some patients.

"What sets this drug apart from the rest is its ability to focus on the inflammation caused by a virus or bacteria," said Jerris Hedges, M.D., M.S., chairman of emergency medicine, OHSU School of Medicine. "Researchers have been studying the reasons behind high temperatures caused by illness for years. However, this is the first drug that can specifically target the pathway causing fever without a noticeable effect on the body's normal housekeeping functions."

A total of 94 patients were involved in the trial. In addition to the testing in Portland, clinical research was conducted in Colorado, Illinois, Kansas, New Jersey, Ohio, Pennsylvania and Texas. Researchers tracked the effect of the medicine over a four-hour period. Following the study, participants received regular checkups to verify that there were no complications caused by the drug.

The Food and Drug Administration is already considering approval of rofecoxib as an anti-inflammatory drug. Past trials show the medication is an effective treatment for arthritis. Approval of rofecoxib as a fever reducer could soon follow.

Research was conducted in conjunction with Merck Research Laboratories in Rahway, New Jersey. The findings are printed in the June edition of Clinical Pharmacology and Therapeutics.
Editors: Dr. Hedges is available for interviews. Call Jim Newman in University News and Publications at 503-494-8231 for more information.

Oregon Health & Science University

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