LOS ANGELES--More than a million Americans may be at risk for bleeding problems due to a genetic characteristic that affects how they metabolize the anticoagulant drug warfarin. The same genetic variation affects metabolism of tolbutamide, taken by diabetics to lower blood sugar, and of phenytoin, an anti-seizure drug. Until now, researchers weren't certain how many people carried this genetic trait.
In new findings presented during the annual meeting of the American Society for Clinical Pharmacology and Therapeutics, Ute Ina Schwarz, MD, of Vanderbilt University Medical School, will explain how prevalent this characteristic is among racial and ethnic groups.She will also describe her discovery of a new, related genetic variation that's likely to affect metabolism of the same drugs, particularly in African-Americans.
"It's important to know when patients have this [characteristic], because when they do, their drug metabolism is changed," Schwarz said. The focus of her research has been cytochrome P450 2C9, a liver enzyme. A specific variation, or polymorphism, in the gene that regulates production of the enzyme will slow the metabolism of warfarin, tolbutamide, and phenytoin. "If there is a decrease in metabolism, you must decrease the dose of warfarin, otherwise complications of bleeding can occur," she explained. In people with slow metabolisms, the active components of drugs remain active longer. Usually, they should take smaller doses.
Schwarz and her colleagues have estimated that this polymorphism, called CYP2C9*3, affects about 8 percent of Caucasians and 2 percent of African Americans. In the course of studying CYP2C9*3, Schwarz and her colleagues discovered a new polymorphism in the same region of the chromosome. The function of the new variation hasn't been studied yet, but Schwarz reports that it is more common among African Americans than CYP2C9*3 and is likely to affect drug metabolism.
Schwarz's research has important implications for the administration of drugs that are widely used--warfarin for use in stroke prevention and following heart valve replacement to prevent complications from blood clots, tolbutamide to lower blood sugar in diabetics, and phenytoin as an anti-seizure agent in people with epilepsy. By determining the prevalence of genetic variations that affect drug metabolism, researchers raise questions concerning the need for screening tools to identify individuals with traits that affect drug metabolism.
Founded in 1900, the ASCPT consists of over 2200 professionals whose primary interest is to promote and advance the science of human pharmacology and therapeutics. The Society is the largest scientific and professional organization serving the discipline of Clinical Pharmacology.
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