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

克拉霉素对丁螺环酮口腔清除率的影响

• 批准号: 7606442
• 负责人: STEPHEN D HALL
• 金额: $ 0.12万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7606442
• 关键词: Anti-Anxiety Agents; Buspirone; CYP3A4 gene; Cirrhosis; Clarithromycin; Computer Retrieval of Information on Scientific Projects Database; Dose; Drug Kinetics; Exhibits; Funding; Goals; Grant; Hepatic; Individual; Institution; Intestines; Label; Oral; Patients; Pharmaceutical Preparations; Randomized; Research; Research Personnel; Resources; Risk; Source; Transjugular intrahepatic portosystemic shunt procedure; United States National Institutes of Health; cytochrome P450 3A; enzyme activity; healthy volunteer; treatment duration

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

这个子项目是许多研究子项目中的一个 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来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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