P450 ACTIVITY AND INTESTINAL GENE EXPRESSION PREDICTS TACROLIMUS BIOAVAILABILITY

P450 活性和肠道基因表达预测他克莫司生物利用度

• 批准号: 6297161
• 负责人: PAUL B WATKINS
• 金额: $ 0.02万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 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/6297161
• 关键词: FK506; biomarker; clinical research; cytochrome P450; gene expression; human subject; kidney transplantation; membrane transport proteins; pharmacokinetics

We will test the hypothesis that the bioavailability of FK506 in stable renal transplant recipients, under steady state conditions, is largely determined by both enteric and hepatic P450 3A4 activity. Furthermore, the effect of the intestinal multi-drug resistance (mdr1) transporter on enteric metabolism and subsequent FK506 bioavailability will be examined. The underlying hypothesis is that interpatient variation in P450 3A4 and mdr1 expression largely accounts for interindividual differences in the oral clearance of FK506.

我们将检验以下假设：在稳态条件下，FK506 在稳定肾移植受者中的生物利用度很大程度上取决于肠道和肝脏 P450 3A4 活性。 此外，还将检查肠道多药耐药性 (mdr1) 转运蛋白对肠道代谢和随后的 FK506 生物利用度的影响。基本假设是 P450 3A4 和 mdr1 表达的患者间差异在很大程度上解释了 FK506 口服清除率的个体间差异。