PHARMACOGENOMICS OF MDR1 IN PATIENTS WITH CYSTIC FIBROSIS (CF)

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这是一项两阶段前瞻性随机研究。 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MDR 1基因组学。基因分型的定量将在研究者现有的实验室进行。第二阶段将是上述患者的子集的交叉随机化，以接受单次口服剂量的探针药物非索非那定，沿着碘酞酸盐（用于GFR测定），伴随（n=8;组1）或不伴随（n=8;组2）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）。 将采集尿液（24小时）和血液（48小时）样本，用于测定药代动力学（非索非那定和碘酞酸盐的肾清除率[GFR]和非索非那定的血浆AUC计算），并将在GCRC中进行。

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.