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

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 肝硬化患者接受经颈静脉肝内门体分流术 (TIPS) 后，肠道 CYP3A 活性显着降低。这些患者预计面临由细胞色素 P450 (CYP) 3A 代谢的药物产生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 CYP 3A 酶活性。由于肝 CYP3A 酶活性降低，肝硬化患者丁螺环酮的口服清除率显着降低。本研究的目标是通过对 12 名接受 TIPS 的肝硬化患者、12 名肝硬化患者和 12 名健康志愿者进行开放标签、随机研究，描述口服丁螺环酮与克拉霉素治疗 7 天后药代动力学的变化。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 之比所反映的相互作用程度。我们预计健康志愿者和没有 TIPS 的肝硬化患者将表现出

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