Bernard Elodie, Goutelle Sylvain, Bertrand Yves, Bleyzac Nathalie
Institut d'Hématologie et d'Oncologie Pédiatrique, Lyon, France.
Laboratoire de Biométrie et Biologie Evolutive, Université Lyon 1, Villeurbanne, France.
Ann Pharmacother. 2014 Dec;48(12):1580-4. doi: 10.1177/1060028014550644. Epub 2014 Oct 3.
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.
This study aimed to quantify the pharmacokinetic drug-drug interaction between CsA and nicardipine, amlodipine, and lacidipine. In all, 51 children who received CsA and CCB concomitantly were included.
Dose-normalized CsA trough blood concentrations significantly increased in patients treated with nicardipine and amlodipine, whereas they remained stable in patients treated with lacidipine.
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.
环孢素（CsA）常导致骨髓移植儿童出现高血压。钙通道阻滞剂（CCB）被认为是治疗CsA诱导的高血压的最佳药物，但它们可能通过抑制CsA代谢的CYP3A4途径或P-糖蛋白来改变CsA的暴露量和疗效。然而，不同CCB对CYP3A4的抑制作用可能有所不同。
本研究旨在量化CsA与尼卡地平、氨氯地平和拉西地平之间的药代动力学药物-药物相互作用。共纳入51例同时接受CsA和CCB治疗的儿童。
接受尼卡地平和氨氯地平治疗的患者中，剂量标准化的CsA谷血浓度显著升高，而接受拉西地平治疗的患者中该浓度保持稳定。
由于拉西地平似乎对CsA的暴露量没有影响，它可能是CCB中治疗儿童CsA所致高血压的最佳选择。
