MCG Gets Technology to Help Optimize Medicine Dosage
News Jan 12, 2006
Technology that helps doctors decide how much medicine to give a specific patient is being used for the first time at the Medical College of Georgia.
"This is being touted as the beginning of personalized medicine," Dr. Stephen C. Peiper, chair of the MCG Department of Pathology says of the first U.S. Food and Drug Administration-cleared pharmacogenetics test that looks at how an individual metabolizes a drug.
"We are talking about a chip-based genetic test that looks at differences between individuals," Dr. Peiper says of the AmpliChip CYP450 Test, developed by Roche Diagnostics, which is designed to analyze variations of the two major genes involved in metabolizing about 25 percent of all drugs.
The test initially will be used to optimize doses of commonly used psychiatric drugs.
"We are very interested in utilizing this technology to help patients get the best treatment and minimize side effects," Dr. Peiper says.
"There is a second test now that has FDA clearance to look at metabolism of a common drug used in chemotherapy and to pick the best dose," says the Georgia Cancer Coalition Distinguished Cancer Clinician and Scientist.
MCG also is interested in a future application that could change the way leukemia and lymphoma are diagnosed and treated.
"We also want to be involved in multi-institutional studies to further define standards that will expand the use of this type of technology."
CYP450 is a major subset of metabolizing genes, and the Roche test looks for variations of two of those genes, CYP2D6 and CYP2C19, says Dr. Zixuan (Zoe) Wang, molecular biologist and scientific director of MCG’s Georgia Esoteric & Molecular Diagnostic Labs, L.L.C.
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 this 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 problem is, if you give somebody who has depression an antidepressant and you give them too low a dose, it’s not going to benefit them and they still have the risk of side effects."
"The person with a great outcome and few side effects doesn’t happen often enough, so patients and doctors often end up switching to try to get the right drug and that right balance," Dr. Buckley says.
"This approach of using genetics to assist in guiding decisions about medications is a very nice advance that has great potential."
"Any test that can help prevent somebody from getting side effects and even help predict whether a drug might be beneficial for them is a huge issue."
"We are grateful to Drs. Peiper and Wang for their efforts to acquire this technology for MCG and excited about the opportunity to pioneer this emergent technology in clinical psychiatry," says Dr Adriana Foster, an expert in schizophrenia and mood disorders.