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.
-end-
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

Related Enzyme Articles from Brightsurf:

Repairing the photosynthetic enzyme Rubisco
Researchers at the Max Planck Institute of Biochemistry decipher the molecular mechanism of Rubisco Activase

Oldest enzyme in cellular respiration isolated
Researchers from Goethe University have found what is perhaps the oldest enzyme in cellular respiration.

UQ researchers solve a 50-year-old enzyme mystery
Advanced herbicides and treatments for infection may result from the unravelling of a 50-year-old mystery by University of Queensland researchers.

Overactive enzyme causes hereditary hypertension
After more than 40 years, several teams at the MDC and ECRC have now made a breakthrough discovery with the help of two animal models: they have proven that an altered gene encoding the enzyme PDE3A causes an inherited form of high blood pressure.

Triggered by light, a novel way to switch on an enzyme
In living cells, enzymes drive biochemical metabolic processes. It is this very ability which allows them to be used as catalysts in biotechnology, for example to create chemical products such as pharmaceutics.

A 'corset' for the enzyme structure
The structure of enzymes determines how they control vital processes such as digestion or immune response.

Could inhibiting the DPP4 enzyme help treat coronavirus?
Researchers and clinicians are scrambling to find ways to combat COVID-19, including new therapeutics and eventually a vaccine.

Bacterial enzyme could become a new target for antibiotics
Scientists discover the structure of an enzyme, found in the human gut, that breaks down a component of collagen.

Chemists create new artificial enzyme
Rajeev Prabhakar, a computational chemist at the University of Miami, and his collaborators at the University of Michigan have created a novel, synthetic, three-stranded molecule that functions just like a natural metalloenzyme, or an enzyme that contains metal ions.

First artificial enzyme created with two non-biological groups
Scientists at the University of Groningen turned a non-enzymatic protein into a new, artificial enzyme by adding two abiological catalytic components: an unnatural amino acid and a catalytic copper complex.

Read More: Enzyme News and Enzyme Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.