PHARMACOGENOMICS OF MDR1 IN PATIENTS WITH CYSTIC FIBROSIS (CF)

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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. 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.