The genes are highly expressed in the liver, which she calls the capital of drug metabolism. "Many drugs work through these pathways," she says. How an individual uses a drug dramatically affects both its efficacy and side effects. "Side effects are the fourth leading cause of death in the United States," Dr. Wang says. "It's a really big issue and most of the side effects are associated with the genotype."

With the newly acquired technology, a blood sample is used to look at gene profile and find whether a person is an ultra-rapid, extensive, intermediate or poor metabolizer of a specific drug.

"If someone is a slow metabolizer, the problem you are going to experience is the drug is not going to be broken down," Dr. Peiper says. "It will stay in the liver at high concentrations for a long time. The problem with that is it usually causes side effects; it may even be toxic. You need to lower the dose for those particular patients. On the other hand, if somebody has a genotype that is ultra-rapid, they will break down the drug very, very fast, so the result is there is not enough drug and they may need to take a higher dose," Dr. Peiper says.

An estimated 5 percent of people are ultra-rapid metabolizers, about 5 percent are slow and most are in the mid-range where the recommended dose of the drug works pretty well, he says.

Generally, physicians look at the recommended dose as well as factors such as age and weight to decide what dosage to prescribe.

"Choosing the best dose of a drug for each individual is challenging and often, it's fair to say, can be more art than science " says Dr. Peter Buckley, chair of the MCG Department of Psychiatry and Health Behavior. "Generally, we start with the lowest dose we think will work because it reduces the risk of side effects. The prob
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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
9-Jan-2006