Pharmacokinetic Drug-Drug Interaction of Calcium Channel Blockers With Cyclosporine in Hematopoietic Stem Cell Transplant Children
Pharmacokinetic Drug-Drug Interaction of Calcium Channel Blockers With Cyclosporine in Hematopoietic Stem Cell Transplant Children
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DOI：
10.1177/1060028014550644
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发表时间：
2014-12-01
影响因子：
2.9
通讯作者：
Bleyzac, Nathalie
中科院分区：
文献类型：
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作者：
Bernard, Elodie;Goutelle, Sylvain;Bleyzac, Nathalie
背景：环孢霉素（CsA）是骨髓移植儿童高血压的常见原因。钙通道阻滞剂（CCBs）被认为是治疗CsA所致高血压的最佳药物，但CCBs可能通过抑制CsA代谢的CYP 3A 4途径或P-gp而改变CsA的暴露量和疗效。然而，对CYP 3A 4的抑制作用可能因CCB而异。方法：本研究旨在量化CsA与尼卡地平、阿托伐他汀和拉西地平之间的药代动力学药物相互作用。共纳入5例同时接受CsA和CCB治疗的I期儿童。结果如下：剂量标准化CsA谷血药浓度显着增加与尼卡地平和顺铂治疗的患者，而他们保持稳定与拉西地平治疗的患者。结论：由于拉西地平似乎对CsA暴露没有影响，因此它可能是治疗儿童CsA引起的高血压的最佳选择。
Background: Cyclosporine (CsA) is frequently responsible for hypertension in bone marrow transplant children. Calcium channel blockers (CCBs) are considered to be the best treatment for CsA-induced hypertension, but they may alter the exposure and the effect of CsA by inhibiting the CYP3A4 pathway of CsA metabolism or P-gp. However, the inhibitory effect on CYP3A4 may vary among CCBs. Methods: This study aimed to quantify the pharmacokinetic drug-drug interaction between CsA and nicardipine, amlodipine, and lacidipine. In all, 5 I children who received CsA and CCB concomitantly were included. Results: Dose-normalized CsA trough blood concentrations significantly increased in patients treated with nicardipine and amlodipine, whereas they remained stable in patients treated with lacidipine. Conclusions: Because lacidipine appears to have no effect on CsA exposure, it may be the best option among CCBs for treating high blood pressure caused by CsA in children.