P-Glycoprotein Function in Peripheral Blood Mononuclear Cells of Myasthenia Gravis Patients Treated with Tacrolimus

• Published in: Biological & pharmaceutical bulletin Vol. 30; no. 2; pp. 291 - 296
• Main Authors: Tanaka, Sachiko, Saito, Toyokazu, Wakata, Nobuo, Hirano, Toshihiko, Oka, Kitaro
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.02.2007; Japan Science and Technology Agency
• Subjects: Adult; Aged; Antibodies - blood; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism; Female; Humans; Immunosuppressive Agents - therapeutic use; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; lymphocyte-blastogenesis; Male; Middle Aged; myasthenia gravis; Myasthenia Gravis - drug therapy; Myasthenia Gravis - metabolism; P-glycoprotein; peripheral-blood mononuclear cell; Receptors, Cholinergic - immunology; Tacrolimus - therapeutic use; tacrolimus hydrate; Treatment Outcome
• ISSN: 0918-6158; 1347-5215; 1347-5215
• DOI: 10.1248/bpb.30.291

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.