期刊
SPRINGERPLUS
卷 4, 期 -, 页码 -出版社
SPRINGER INTERNATIONAL PUBLISHING AG
DOI: 10.1186/s40064-015-0802-4
关键词
Doxorubicin; Angiotensin Converting Enzyme Inhibitors; Pharmacokinetics; Cardioprotection; Drug interaction; Enalapril; Breast cancer
资金
- National Cancer Institute [P30 CA77598]
Purpose: Doxorubicin (DOX) chemotherapy can cause cardiac complications. Angiotensin converting enzyme inhibitors (ACEI) may protect against these complications. We performed a pharmacokinetics (PK) study to determine whether DOX levels are altered in the presence of ACEI. Methods: In this randomized, cross-over, single-blinded drug-drug interaction study, 19 women with breast cancer prescribed DOX and cyclophosphamide every 14 days received one cycle of DOX chemotherapy with ACEI enalapril 10 mg daily and another cycle of DOX with placebo. Blood samples for DOX and doxorubicinol were drawn at baseline, 0.5, 1.0, 2.0, 4.0, 24.0 and 48.0 hours after infusion with and without ACEI enalapril. Correlative laboratories were also obtained. PK data was analyzed using non compartmental methods and DOX and doxorubicinol area under the curve (AUC) 0 to infinity, Cmax and half-life were estimated. Paired t-tests were used to determine whether DOX and its metabolite were altered with the use of enalapril (P < 0.05). Results: 17 women (median age 45 years) received 60 mg/m2 DOX every two weeks for four cycles. Mean (SD) AUC0- infinity for DOX and doxorubicinol with enalapril exposure was 1185.56 (44.64) hr*ng/ml and 1040 (80.6) hr*ng/ml, respectively. AUC0- infinity for DOX and doxobubicinol without enalapril was 1167.73 (45.26) hr*ng/ml and 1056.32 (92.03) hr*ng/ml, respectively. There is no interaction between DOX and enalapril. Enalapril was tolerated (33% grade 1 dizziness). Conclusion: ACEI, enalapril, does not appear to alter the PK of DOX. Ongoing efforts to determine the effectiveness of ACEI as a cardioprotective agent in women receiving DOX chemotherapy should be continued.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据