INFLUENCE OF DRUG TRNSPRTR GENETICS ON ROSIGLITAZONE PHRMCOKINS IN HLTHY VOLNTRS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 罗格列酮(文迪雅)是美国食品和药物管理局(FDA)批准的用于治疗2型糖尿病的药物。人们对罗格列酮的反应方式不同。对于一些人来说，这是一种有效的药物，但在另一些人身上却效果不佳。这可能是血液中罗格列酮含量不同的结果。这也可能是由于药物在体内吸收、分解或运输的方式不同所致。药物在体内的作用方式可能会受到一个人的基因构成(或DNA)的影响。这项临床研究的目的是确定一个人的基因构成是否会影响血液中罗格列酮的量。将要研究的遗传差异是在OATP1B1药物转运蛋白基因中发现的。这种蛋白质对包括罗格列酮在内的许多药物进入肝脏的转运非常重要。 虽然罗格列酮被用来治疗糖尿病，但我们正在研究这种药物在健康人身上的应用。受试者将被预先筛查OATP1B1药物转运蛋白基因的遗传差异。DNA采集的预筛选方法将是漱口水样本。如果受试者与所需的基因相匹配，他们将被要求返回进行进一步的实验室测试，以确保他们是健康的，并可以参与研究。如果受试者身体健康，他们将被要求参加GCRC的24小时通宵学习。在这一24小时的访问中，受试者将在早上接受单剂量的罗格列酮口服。将在24小时内在多个时间点采集血液样本，以确定血液中罗格列酮的含量。这项研究是了解一个人的基因构成影响血液中罗格列酮含量的早期步骤。

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.