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

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 funct...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2007, Vol.30(2), pp.291-296
Main Authors: Tanaka, Sachiko, Hirano, Toshihiko, Saito, Toyokazu, Wakata, Nobuo, Oka, Kitaro
Format: Article
Language:English
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
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Summary: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.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.30.291