DEXAMETHASONE ON CYTOCHROME P450 3A4 ACTIVITY

地塞米松对细胞色素 P450 3A4 活性的影响

• 批准号: 6297273
• 负责人: CELESTE M LINDLEY
• 金额: $ 0.02万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6297273
• 关键词: clinical research; cytochrome P450; dexamethasone; drug interactions; enzyme activity; enzyme induction /repression; human subject; liver metabolism; oral administration; pharmacokinetics

This study will test the hypotheses that oral dexamethasone (8 mg, PO BID for 5 days) alters hepatic and/or intestinal cytochrome P450 3A4 (CYP3A4) activity in healthy volunteers. The CYP3A4 pathway metabolizes approximately half of orally administered medications. Dexamethasone is administered to a large number of cancer patients as part of their chemotherapy regimen, to decrease the likelihood of chemotherapy induced emesis or other chemotherapy associated side effects. Human heptocyte and a small amount of clinical data demonstrate CYP3A4 activity is induced by dexamethasone. Alterations in CYP3A4 activity can affect the bioavailability and clearance of antineoplastics metabolized by this pathway, therefore potentially altering their systemic exposure, efficacy and/or toxicity.

本研究将验证口服地塞米松(8 mg，连续5天)对健康志愿者肝脏和/或肠道细胞色素P450 3A4(CYP3A4)活性的影响。在口服给药的药物中，大约有一半是通过细胞色素P3A4途径代谢的。地塞米松作为化疗方案的一部分，用于大量癌症患者，以减少化疗引起呕吐或其他化疗相关副作用的可能性。人肝细胞和少量临床资料表明，细胞色素P3A4活性是地塞米松诱导的。细胞色素P3A4活性的改变可以影响通过该途径代谢的抗肿瘤药物的生物利用度和清除量，从而潜在地改变其全身暴露、疗效和/或毒性。