INFLUENCE OF DRUG TRNSPRTR GENETICS ON ROSIGLITAZONE PHRMCOKINS IN HLTHY VOLNTRS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Rosiglitazone (Avandia¿) is approved by the Food and Drug Administration (FDA) and is used for the treatment of type 2 diabetes. People differ in the way they respond to rosiglitazone. It is an effective medication for some people, but it does not work as well in other people. This may be a result of differences in the amount of rosiglitazone in the blood. It also may be due to differences in the way that the drug is absorbed, broken-down, or transported in the body. The way a medication works in the body may be affected by a person's genetic make-up (or DNA). The purpose of this clinical study is to determine if a person's genetic make-up affects the amount of rosiglitazone in the blood. The genetic differences that will be studied are found in the OATP1B1 drug transporter gene. This protein is important for transporting many drugs, including rosiglitazone, into the liver. Although rosiglitazone is used to treat diabetes, we are studying the medication in healthy people. Subjects will be pre-screened for genetic differences in the OATP1B1 drug transporter gene. The pre-screening method for DNA collection will be a mouthwash sample. If a subject matches a needed genotype, they will be asked to return for further laboratory testing to ensure that they are healthy and can participate in the study. If the subject is healthy, they will be asked to participate in a 24-hour overnight study at the GCRC. During this 24-hour visit, subjects will receive a single, oral dose of rosiglitazone in the morning. Blood samples will be drawn at multiple time points over a 24-hour period to determine the amount of rosiglitazone in the blood. This study is an early step to see a person's genetic make-up affects the amount of rosiglitazone in the blood.