Herb-Drug Glucuronidation Interactions

草药-药物葡萄糖醛酸化相互作用

• 批准号: 8142725
• 负责人: REGINALD F FRYE
• 金额: $ 28.4万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2013-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8142725
• 关键词: Address; Affect; American; Biological Availability; Blood; Clinical; Clinical Research; Cytochrome P450; Data; Drug Interactions; Drug Kinetics; Enzymes; Epigallocatechin Gallate; Ginkgo biloba; Glucuronides; Goals; Green tea; Health; Health Personnel; Herb; Herb-Drug Interactions; Human; Immunosuppressive Agents; Incubated; Individual; Intestines; Knowledge; Laboratories; Liver Microsomes; Mediating; Metabolism; Microsomes; Modeling; Morbidity - disease rate; Mycophenolic Acid; P-Glycoprotein; Pharmaceutical Preparations; Plant Leaves; Prevalence; Process; Public Health; Publishing; Raloxifene; Reporting; Research; Resources; Risk; Route; System; Testing; Therapeutic; Transferase; Translational Research; Uridine Diphosphate; Work; base; clinically relevant; drug metabolism; evidence base; experience; healthy volunteer; in vivo; innovation; man; mortality; pre-clinical; public health relevance; response

DESCRIPTION (provided by applicant): Millions of Americans use herbal supplements to promote their health and wellness, many of them in combination with prescription medications. Accordingly, serious adverse herb- drug interactions resulting from the induction or inhibition of cytochrome P450 enzymes and/or the efflux transporter P-glycoprotein have been reported. However, there is a gap in our evidence-based knowledge regarding the potential of herbal supplements to interact with medications that undergo conjugative metabolism by uridine diphosphate glucuronosyl transferase (UGT) enzymes. Our laboratory has recently identified herbal supplements that strongly inhibit UGT-mediated metabolism. Based on these data, the objective of this application is to determine the extent to which commonly used herbal supplements can inhibit UGT enzymes in humans. The central hypothesis is that taking herbal supplements will alter the pharmacokinetics of a drug eliminated predominately by UGT-mediated metabolism. The goals of this project are to determine in healthy volunteers: 1) the effect of prolonged Ginkgo biloba administration on mycophenolic acid pharmacokinetics; and 2) the effect of green tea leaf extract administration on raloxifene pharmacokinetics. These drugs represent two of the top selling medications for which glucuronidation is the primary route of elimination; increased blood concentrations for each of these drugs can have dire consequences. It is important for human health to understand how herbal supplements influence the UGT-mediated metabolism of medications, as this will fill a significant gap in knowledge. This translational research will provide critical information on the extent to which selected herbal supplements alter the disposition of mycophenolic acid and raloxifene, two clinically important UGT substrates. PUBLIC HEALTH RELEVANCE: Herb-drug interactions continue to be a significant public health concern and the prevalence of herbal supplement use is substantial. The research proposed is significant because it is expected to provide evidence-based knowledge on the potential for herb-drug glucuronidation interactions, which will ultimately help health care providers anticipate potential herb-drug interactions and contribute to rational adjustments in therapy management.

描述（由申请人提供）：数百万美国人使用草药补充剂来促进他们的健康，其中许多与处方药相结合。因此，已报告了诱导或抑制细胞色素P450酶和/或外排转运蛋白P-糖蛋白导致的严重不良草药相互作用。然而，有一个差距，在我们的循证知识的潜力，草药补充剂相互作用的药物进行共轭代谢的尿苷二磷酸葡萄糖醛酸转移酶（UGT）酶。我们的实验室最近发现了强烈抑制UGT介导的代谢的草药补充剂。基于这些数据，本申请的目的是确定常用草药补充剂抑制人体UGT酶的程度。中心假设是服用草药补充剂将改变主要由UGT介导的代谢消除的药物的药代动力学。本项目的目的是在健康志愿者中确定：1）长期服用银杏叶对麦考酚酸药代动力学的影响; 2）服用绿色茶叶提取物对雷洛昔芬药代动力学的影响。这些药物代表了葡萄糖醛酸化是主要消除途径的两种最畅销的药物;这些药物中每一种的血药浓度增加都可能产生可怕的后果。了解草药补充剂如何影响UGT介导的药物代谢对人类健康至关重要，因为这将填补知识的重大空白。这项转化研究将提供关键信息的程度，选择草药补充剂改变麦考酚酸和雷洛昔芬，两个临床上重要的UGT底物的处置。 公共卫生相关性：草药-药物相互作用仍然是一个重要的公共卫生问题，草药补充剂的使用率很高。这项研究具有重要意义，因为它有望为草药-药物葡萄糖醛酸化相互作用的潜力提供基于证据的知识，这将最终帮助医疗保健提供者预测潜在的草药-药物相互作用，并有助于合理调整治疗管理。