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 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.
Tanaka
Sachiko
S
Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Science, and Department of Neurology, Kitasato University East Hospital, Kanagawa, Japan. sachiko@ps.toyaku.ac.jp
Hirano
Toshihiko
T
Saito
Toyokazu
T
Wakata
Nobuo
N
Oka
Kitaro
K
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000188:drug therapy / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000276:immunology; D016559:Tacrolimus / Q000627:therapeutic use*; D016896:Treatment Outcome
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000906:Antibodies; D007166:Immunosuppressive Agents; D011950:Receptors, Cholinergic; D016559:Tacrolimus