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标题：P-Glycoprotein Function in Peripheral Blood Mononuclear Cells of Myasthenia Gravis Patients Treated with Tacrolimus
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作者：Sachiko Tanaka ; Toshihiko Hirano ; Toyokazu Saito 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2007
卷号：30
期号：2
页码：291-296
DOI：10.1248/bpb.30.291
出版社：The Pharmaceutical Society of Japan
摘要：Tacrolimus hydrate (FK506) reduces the symptoms of myasthenia gravis (MG) due to its immunosuppressive properties. A drug efflux pump P-glycoprotein (P-gp) actively transports FK506 out of target cells, thereby reducing their efficacy. We investigated the influence of FK506 therapy on the P-gp function of peripheral-blood mononuclear cells (PBMCs) in MG patients. Six MG patients treated with FK506 (MG(FK+)), four MG patients treated without FK506 administration (MG(FK−)), and 18 healthy subjects were included in this study. P-gp function was estimated by transporter activity that was inferred from a decrease in fluorescent P-gp substrate Rhodamine 123 (Rh123) and its inhibition by cyclosporine A (CsA). The P-gp efflux function in MG (FK+) patients assessed by the Kolmogorov–Smirnov (KS) statistic D was lower than in the healthy subjects ( p =0.0084). However, PBMC sensitivity to FK506 in MG (FK+) patients was significantly higher compared to that of the healthy subjects ( p =0.02). There was a significant correlation between the Rh123 efflux activity and PBMC sensitivity to FK506 in vitro ( p =0.011). The data raise the possibility that FK506 treatment attenuated P-gp function in the PBMCs of the MG patients.
关键词：P-glycoprotein;peripheral-blood mononuclear cell;myasthenia gravis;tacrolimus hydrate;lymphocyte-blastogenesis