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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。在经颈静脉肝内门体分流术(TIPS)的肝硬变患者中，肠道细胞色素P3A活性明显降低。这些患者预计会面临由细胞色素P450(CYP)3A代谢的药物的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，它高度依赖于CYP 3A酶的活性来消除。在肝硬变患者中，丁螺环酮的口服清除量显著降低，原因是肝脏细胞色素P3A酶活性降低。本研究的目的是通过对12名有TIPS的肝硬化症患者、12名肝硬化症患者和12名健康志愿者进行一项开放的随机研究，来表征口服丁螺环酮和克拉霉素治疗7天后的药代动力学变化。我们将比较三组患者服药后丁螺环酮AUC与服药前丁螺环酮AUC的比值所反映的相互作用程度。我们期望健康的志愿者和没有提示的肝硬化症患者将展示

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