Robertsen Ida, Vethe Nils Tore, Midtvedt Karsten, Falck Pål, Christensen Hege, Åsberg Anders
*Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo; and Departments of †Pharmacology, and ‡Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Ther Drug Monit. 2015 Oct;37(5):675-80. doi: 10.1097/FTD.0000000000000185.
Everolimus (EVE) is an immunosuppressive drug dosed according to therapeutic drug monitoring in renal transplant recipients. The primary site of action is within activated lymphocytes. EVE is a substrate of the efflux transporter ABCB1 also known as P-glycoprotein. Limited data exist regarding a possible association between whole blood and intralymphocyte concentrations of EVE and the potential influence of ABCB1.
Twelve renal transplant recipients (5 men and 7 women) treated with EVE underwent a pharmacokinetic investigation where EVE concentrations in whole blood and in peripheral blood mononuclear cells (PBMC) were determined within a dosing interval. In addition, the activity of ABCB1 in PBMC was determined using the Rhodamine123 efflux assay and the patients' genotypes of ABCB1 were determined.
There was a significant correlation between EVE AUC0-12 in whole blood and in PBMC (r = 0.90, P < 0.01), and no association was demonstrated between the ABCB1 activity and EVE PBMC/whole blood ratio of trough concentrations (r = 0.23, P = 0.76). Furthermore, ABCB1 1236C>T, 3435C>T, and 2677G>T/A polymorphism did not influence EVE AUC0-12 PBMC/whole blood ratio.
The results revealed a significant association between EVE whole blood and PBMC concentrations, suggesting that ABCB1-mediated efflux from PBMC to be of minor importance for the distribution of EVE.
依维莫司（EVE）是一种用于肾移植受者的免疫抑制药物，需根据治疗药物监测进行给药。其主要作用部位在活化淋巴细胞内。EVE是外排转运蛋白ABCB1（也称为P-糖蛋白）的底物。关于EVE全血浓度与淋巴细胞内浓度之间可能的关联以及ABCB1的潜在影响，现有数据有限。
12例接受EVE治疗的肾移植受者（5名男性和7名女性）进行了药代动力学研究，在给药间隔内测定全血和外周血单个核细胞（PBMC）中的EVE浓度。此外，使用罗丹明123外排试验测定PBMC中ABCB1的活性，并确定患者的ABCB1基因型。
全血和PBMC中EVE的AUC0-12之间存在显著相关性（r = 0.90，P < 0.01），ABCB1活性与谷浓度时EVE的PBMC/全血比值之间未显示出关联（r = 0.23，P = 0.76）。此外，ABCB1的1236C>T、3435C>T和2677G>T/A多态性不影响EVE的AUC0-12 PBMC/全血比值。
结果显示EVE全血浓度与PBMC浓度之间存在显著关联，表明ABCB1介导的从PBMC向外的外排在EVE分布中作用较小。
