CYP3A PROBES AND HEPATIC BLOOD FLOW

CYP3A 探针和肝血流

• 批准号: 7603355
• 负责人: Evan D. Kharasch
• 金额: $ 0.38万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603355
• 关键词: Affect; Alfentanil; Blood flow; Computer Retrieval of Information on Scientific Projects Database; Cytochromes; Development; Funding; Grant; Hepatic; Human; Institution; Investigation; Liver; Metabolism; Midazolam; Pharmaceutical Preparations; Research; Research Personnel; Resources; Source; Testing; United States National Institutes of Health; healthy volunteer; in vivo; theories

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 ideal in vivo probe for the activity of cytochrome P4503A (CYP3A) in humans remains unidentified. The two most commonly used and scientifically promising probes are the clearances of midazolam and alfentanil. Clearances may be influenced by metabolism and/or hepatic blood flow. Alfentanil is a low- (or possible intermediate-) extraction drug, and midazolam is an intermediate extraction drug. According to conventional theory, the clearance of low-extraction drugs is independent of hepatic bloodflow, while the clearance of intermediate-extraction drugs is affected by liver blood flow. However the effect of liver blood flow on the clearance of midazolam and alfentanil has not been evaluated. This investigation will test the hypothesis is that alteration in liver blood flow will have no effect on alfentanil clearance, and that alteration in liver blood flow will have a greater effect on midazolam clearance than on alfentanil clearance. This investigation, in healthy volunteers, will up-and down-regulate hepatic blood flow, and assess the effect on the systemic and first-pass clearances of alfentanil and midazolam. Identification of the drug which is less affected by liver blood flow will help towards the development of an ideal CYP3A probe.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 人类细胞色素P4503a（CYP3A）活性的理想体内探针仍然不明。 两种最常用且科学上有希望的探针是咪达唑仑和阿尔芬太尼的清除。 清除可能会受到代谢和/或肝血流的影响。 Alfentanil是一种低（或可能的中间）提取药物，咪达唑仑是一种中间提取药物。 根据常规理论，低牵引力药物的清除率与肝血流无关，而中等抽吸药的清除受肝血流的影响。 然而，尚未评估肝血流对咪达唑仑和阿尔平坦清除率的影响。 这项研究将检验假设是，肝血流的改变对阿尔平坦的清除没有影响，而肝血流的改变对咪达唑仑清除率的影响要比对阿芬太尼清除率更大。 在健康志愿者中，这项调查将向上和下调肝血流，并评估对阿尔芬太尼和咪达唑仑的系统性和第一频道清除的影响。 鉴定受肝血流影响较小的药物将有助于开发理想的CYP3A探针。