EFFECT OF CLARITHROMYCIN ON THE ORAL CLEARANCE OF BUSPIRONE IN PATIENTS WITH

该子项目是利用 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来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 经颈静脉肝内门体分流术（TIPS）患者的肠道CYP 3A活性显著降低。预计这些患者存在由细胞色素P450（CYP 3A）代谢的药物过度药理作用的风险。丁螺环酮是一种广泛使用的抗焦虑药物，其消除高度依赖于β 3A酶活性。丁螺环酮的口服清除率在肝硬化患者中由于肝脏CYP 3A酶活性降低而显著降低。本研究的目的是通过对12名TIPS治疗的哮喘患者、12名哮喘患者和12名健康志愿者进行开放标签、随机化研究，表征克拉霉素治疗7天后丁螺环酮口服给药的药代动力学变化。我们将比较三组中克拉霉素给药后丁螺环酮AUC与克拉霉素给药前丁螺环酮AUC的比值所反映的相互作用程度。我们预计，健康志愿者和没有TIPS的患者将表现出

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. The intestinal CYP3A activity is markedly diminished in cirrhotics with transjugular intrahepatic portasystemic shunts (TIPS). These patients are expected to be at risk for excessive pharmacological effects of drugs that are metabolized by Cytochrome P450 (CYP) 3A. Buspirone is a widely used anxiolytic medication that is highly dependent on CYP 3A enzyme activity for elimination. The oral clearance of buspirone is significantly reduced in individuals with cirrhosis due to decrease in hepatic CYP3A enzyme activity. The goal of the current study is to characterize the change in the pharmacokinetics of orally administered buspirone with 7 day treatment of clarithromycin by conducting an open label, randomized study of 12 cirrhotics with TIPS, 12 cirrhotics and 12 healthy volunteers. We will compare the extent of interaction as reflected in the ratio of buspirone AUC following clarithromycin dosing to the buspirone AUC before clarithromycin dosing in the three groups. We expect that healthy volunteers and cirrhotics without TIPS will exhibit