Blaes Anne, Duprez Daniel, Defor Todd, Shanley Ryan, Beckwith Heather, Haddad Tufia, Potter David, Yee Douglas, Sanghavi Kinjal, Jacobson Pamala
Division of Hematology/Oncology/Transplantation, University of Minnesota, 420 Delaware Street, S.E., MMC 480, Minneapolis, MN 55455 USA.
University of Minnesota, Division of Cardiology, Minneapolis, MN USA.
Springerplus. 2015 Jan 23;4:32. doi: 10.1186/s40064-015-0802-4. eCollection 2015.
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.
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).
17 women (median age 45 years) received 60 mg/m2 DOX every two weeks for four cycles. Mean (SD) AUC0- ∞ for DOX and doxorubicinol with enalapril exposure was 1185.56 (44.64) hrng/ml and 1040 (80.6) hrng/ml, respectively. AUC0- ∞ for DOX and doxobubicinol without enalapril was 1167.73 (45.26) hrng/ml and 1056.32 (92.03) hrng/ml, respectively. There is no interaction between DOX and enalapril. Enalapril was tolerated (33% grade 1 dizziness).
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.
阿霉素（DOX）化疗可导致心脏并发症。血管紧张素转换酶抑制剂（ACEI）可能预防这些并发症。我们进行了一项药代动力学（PK）研究，以确定在ACEI存在的情况下DOX水平是否会改变。
在这项随机、交叉、单盲的药物相互作用研究中，19名每14天接受DOX和环磷酰胺治疗的乳腺癌女性患者接受了一个周期的DOX化疗，同时每日服用10 mg的ACEI依那普利，另一个周期的DOX化疗则服用安慰剂。在输注有或没有依那普利的DOX后，于基线、0.5、1.0、2.0、4.0、24.0和48.0小时采集血样检测DOX和阿霉素醇。还获取了相关实验室检测结果。使用非房室模型方法分析PK数据，并估算DOX和阿霉素醇从0至无穷大的曲线下面积（AUC）、Cmax和半衰期。采用配对t检验来确定使用依那普利后DOX及其代谢产物是否发生改变（P < 0.05）。
17名女性（中位年龄45岁）每两周接受60 mg/m² DOX治疗，共四个周期。DOX和阿霉素醇在有依那普利暴露情况下的平均（标准差）AUC0-∞分别为1185.56（44.64）hrng/ml和1040（80.6）hrng/ml。无依那普利时DOX和阿霉素醇的AUC0-∞分别为1167.73（45.26）hrng/ml和1056.32（92.03）hrng/ml。DOX与依那普利之间不存在相互作用。依那普利耐受性良好（33%为1级头晕）。
ACEI依那普利似乎不会改变DOX的药代动力学。应继续努力确定ACEI作为接受DOX化疗女性的心脏保护剂的有效性。
