Featured Research

from universities, journals, and other organizations

Variation In Genetic Make-up Determines Each Person's Reaction To Popular Painkillers

Date:
January 5, 2006
Source:
American Gastroenterological Association
Summary:
A study published in the January issue of the American Gastroenterological Association (AGA) journal Gastroenterology found a difference in how people responded to popular painkillers and that up to 30 percent of this variability can be attributed to an individual's genetic make-up. This variation can influence both how useful the drugs are in affording relief from pain and inflammation, and the number and severity of the adverse effects.

A study published in the January issue of the American Gastroenterological Association (AGA) journal Gastroenterology found a difference in how people responded to popular painkillers and that up to 30 percent of this variability can be attributed to an individual's genetic make-up. This variation can influence both how useful the drugs are in affording relief from pain and inflammation, and the number and severity of the adverse effects. This evaluation is perhaps the most rigorous look at how people vary in their response to drugs and was designed as part of a strategy to determine genetic and other markers that might help predict response and safety of these drugs, including susceptibility to cardiovascular complications.

The study looked at people taking two popular painkillers--rofecoxib (Vioxx, Merck) and celecoxib (Celebrex, Pfizer)--known as COX-2 inhibitors. During the past two years, evidence has emerged that COX-2s confer a risk of heart attack and stroke, resulting in two of the drugs in this class being withdrawn from the market and a black box warning being issued for a third drug.

"The use of any drug involves a mix of benefits and risks. The problems with COX-2 inhibitors were real, but involved less than 2 percent of patients who were taking them," said Garret A. FitzGerald, MD, study author from the University of Pennsylvania School of Medicine. "Because we often underestimate just how much people differ in their response to the same dose of the same drug, there is a need to develop diagnostic methods to identify those patients at an increased risk of cardiovascular events and explore this variability in drug response to move toward an individualized approach in drug development."

Researchers at the University of Pennsylvania examined the variability, both within and between subjects, in response to celecoxib and rofecoxib, in a randomized, double-blind, placebo controlled study. Screening, enrollment and follow-up of healthy study volunteers was performed between January 2002 and January 2004. The study was conducted on 50 healthy volunteers between the ages of 21 and 43 years old who received a single dose of placebo, celecoxib and rofecoxib in random order. This was done to allow researchers a direct comparison of the responses to the drugs within the same subjects. Five of the patients went through the entire protocol five times to assess variability within individuals.

According to study authors, different factors in the environment result in a variety of responses from an individual who is dosed with the same drug at different times. This effect is seen even when as many variables as possible are standardized or controlled for. Approximately 30 percent of the variability found in patients was attributable to differences between individuals, suggesting the contribution of genetics to a variety of biomarkers of drug response. The study also illustrates that even healthy individuals without a recognized risk of disease respond quite differently to the drugs.

Previous studies have shown that rofecoxib and celecoxib result in a small number of the people who were apparently at a low-risk of cardiovascular disease initially, proceeding to increase that risk to the point that culminates in heart attack and stroke following prolonged use of these drugs. According to researchers, exploiting this variability could permit management of the cardiovascular risk of COX-2 inhibitors, while preserving their efficacy for patients most likely to benefit from them and determining how these drugs might be administered to people initially at low risk for cardiovascular disease.

"Typically when a drug causes hazardous side effects, the reaction is to suggest that people reduce the dosage they are taking. However, this has often been followed by withdrawal of the drug from the market when the problems are not eliminated," said FitzGerald. "These findings highlight that while a lower dose may reduce the likelihood of problems on average, it will not eliminate them on an individual level because there is such a marked variability in how each person reacts to these drugs based on their genetic make-up."

Study authors are hopeful that this work will provide an impetus for the development of a science-based approach to risk management. Exploitation of variability in response can lead to tests which identify patients most likely to benefit or suffer from harmful side effects caused by these drugs. "This study provides a starting point for the development of diagnostics that allow the medical and research communities to conserve benefits while managing the risks of COX-2 inhibitors," said FitzGerald.

###

This study was supported by grants from the National Heart, Lung and Blood Institute, the National Center for Research Resources, the American Heart Association, the Wellcome Trust and Orchid Biosciences. Genotyping was performed at the Genomics Institute of Novartis Foundation.

More information is available at www.gastro.org.

About the AGA
The American Gastroenterological Association (AGA) is dedicated to the mission of advancing the science and practice of gastroenterology. Founded in 1897, the AGA is the oldest medical-specialty society in the United States. Comprised of two non-profit organizations--the AGA and the AGA Institute--our more than 14,500 members include physicians and scientists who research, diagnose and treat disorders of the gastrointestinal tract and liver. The AGA, a 501(c6) organization, administers all membership and public policy activities, while the AGA Institute, a 501(c3) organization, runs the organization's practice, research and educational programs. On a monthly basis, the AGA Institute publishes two highly respected journals, Gastroenterology and Clinical Gastroenterology and Hepatology. The organization's annual meeting is Digestive Disease Week, which is held each May and is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.

About Gastroenterology
Gastroenterology, the official journal of the AGA, is the most prominent journal in the subspecialty and is in the top one percent of indexed medical journals internationally. The journal publishes clinical and basic studies of all aspects of the digestive system, including the liver and pancreas, as well as nutrition. The journal is abstracted and indexed in Biological Abstracts, CABS, Chemical Abstracts, Current Contents, Excerpta Medica, Index Medicus, Nutrition Abstracts and Science Citation Index. For more information, visit www.gastrojournal.org.


Story Source:

The above story is based on materials provided by American Gastroenterological Association. Note: Materials may be edited for content and length.


Cite This Page:

American Gastroenterological Association. "Variation In Genetic Make-up Determines Each Person's Reaction To Popular Painkillers." ScienceDaily. ScienceDaily, 5 January 2006. <www.sciencedaily.com/releases/2006/01/060105085659.htm>.
American Gastroenterological Association. (2006, January 5). Variation In Genetic Make-up Determines Each Person's Reaction To Popular Painkillers. ScienceDaily. Retrieved April 18, 2014 from www.sciencedaily.com/releases/2006/01/060105085659.htm
American Gastroenterological Association. "Variation In Genetic Make-up Determines Each Person's Reaction To Popular Painkillers." ScienceDaily. www.sciencedaily.com/releases/2006/01/060105085659.htm (accessed April 18, 2014).

Share This



More Health & Medicine News

Friday, April 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. Video provided by Newsy
Powered by NewsLook.com
Obama: 8 Million Healthcare Signups

Obama: 8 Million Healthcare Signups

AP (Apr. 17, 2014) President Barack Obama gave a briefing Thursday announcing 8 million people have signed up under the Affordable Care Act. He blasted continued Republican efforts to repeal the law. (April 17) Video provided by AP
Powered by NewsLook.com
Is Apathy A Sign Of A Shrinking Brain?

Is Apathy A Sign Of A Shrinking Brain?

Newsy (Apr. 17, 2014) A recent study links apathetic feelings to a smaller brain. Researchers say the results indicate a need for apathy screening for at-risk seniors. Video provided by Newsy
Powered by NewsLook.com
Could Even Casual Marijuana Use Alter Your Brain?

Could Even Casual Marijuana Use Alter Your Brain?

Newsy (Apr. 16, 2014) A new study conducted by researchers at Northwestern and Harvard suggests even casual marijuana use can alter your brain. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins