PHARMACOGENOMICS OF MDR1 IN PATIENTS WITH CYSTIC FIBROSIS (CF)

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。 这是一项两阶段的前瞻性随机研究。在第一阶段，研究人员将从单个血液样本的PBMC中确定40名受试者(20名CF和20名正常志愿者)的MDR1基因组学。基因分型的量化将在调查人员现有的实验室进行。第二阶段将对上述患者的一组患者进行交叉随机分组，接受单剂量口服探针药物非索非那定，同时服用异硫氨基甲酸酯(用于GFR测定)(n=8；第1组)或不服用(n=8；第2组)丙磺舒(通过OATP-有机阴离子转运多肽抑制探针药物的胆汁和肾脏分泌)。将进行尿液(24小时)和血液(48小时)采样以确定药代动力学(肾清除非非那定和硫代氨基甲酸酯[GFR]以及计算非非那定的血浆AUC)，并将在GCRC上进行。

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. This is a two-phase prospective randomized study. In the first phase, the investigators will determine from PBMCs from a single blood sample, the MDR1 genomics in 40 subjects (20 CF and 20 normal volunteers). The quantification of the genotyping will be performed in the investigators' existing laboratories. The second phase will be a cross-over randomization of a subset of the aforementioned patients to receive a single oral dose of the probe drug fexofenadine, along with iothalamate (for GFR determination) with (n=8; group 1) or without (n=8; group 2) probenecid (to inhibit biliary and renal secretion of probe drug by OATP - organic anion transporting polypeptide). Urine (24hours) and blood (48 hours) sampling will be performed for determination of pharmacokinetics (renal clearance of fexofenadine and iothalamate [GFR] and calculation of plasma AUC of fexofenadine), and will be performed on the GCRC.