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

点击翻译按钮获取中文摘要

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