THE EFFECT OF P450 3A ACTIVITY ON THE PHARMACOKINETICS OF DOCETAXEL (TAXOTERE)

P450 3A 活性对多西他赛（泰索帝）药代动力学的影响

• 批准号: 6113475
• 负责人: JOANN S HIRTH
• 金额: $ 2.14万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6113475
• 关键词: clearance rate; clinical research; cytochrome P450; drug adverse effect; drug metabolism; drug screening /evaluation; human subject; human therapy evaluation; liver neoplasms; neoplasm /cancer chemotherapy; paclitaxel; pharmacokinetics

Docetaxel (Taxotere) is a new chemotherapeutic agent which has shown promise in the treatment of various malignancies including cancers of the breast, lung, ovary, stomach, head and neck, bladder, and soft tissue sarcomas. Docetaxel undergoes metabolism by cytochrome P450 3A in human liver microsomes. Patients treated with the same dose of docetaxel per body surface area exhibit interpatient variation in clearance and degree of toxicity. We hypothesize that cytochrome P450 3A is rate limiting in the elimination of docetaxel and that changes in P450 3A activity will result in interpatient and intrapatient variation in docetaxel's clearance.

多西紫杉醇（Taxotere）是一种新型化疗药物，已显示 有望治疗包括癌症在内的各种恶性肿瘤 乳房、肺、卵巢、胃、头颈、膀胱和软组织 组织肉瘤。 多西紫杉醇通过细胞色素 P450 3A 进行代谢 在人肝微粒体中。 接受相同剂量治疗的患者 多西他赛每体表面积表现出患者间差异 清除率和毒性程度。 我们假设细胞色素 P450 3A 是多西紫杉醇消除的速率限制，并且变化 P450 3A 活性将导致患者间和患者内变异 在多西他赛的清除率中。