血清中のタクロリムス濃度の変動因子に関する検討 : 血清タンパク結合の観点から

概要

論文の詳細を見る
Tacrolimus (FK506), which is a potent imuunosuppressive drug, has the excellent effect for prevention of rejection after on organ transu;oanttation. Although the pharmacological activity of FK506 depends on its serum concentratio, the serum oncentration of FK506 is widely fluctuated. We hypothesized that the change of FK506 serum concentration is concerned with the portein binding of FK506, because it is well-known that FK506 bind to serum proteins strongly in general. However, the change factors of FK506 serum concentration were not studied. Therefore, the present study was undertaken to investigate the relationship between the change of FK506 serum concentration and serum protein bindgin of FK506, as well as to identify the binding sites of FK506. Binding activities of FK506 to serum, human serum albumin (HAS), α_1-acid glycoprotein (AGP) and human immunoglobulin (IgG) were examined by ultrafiltration method. Serum concentraiton of FK506 was only enevated by the increment of AGP concentration in whole blood system. This means that FK506 transferred from blood cells to serum with increasing AGP oncentration. In the study of binding sites of FK506, it is obvious that FK506 bind to the overlapping region of acidic and basic drug binding site on AGP molecule. It is important to check AGP serum concentraiton for a dosage plan of FK506.
九州保健福祉大学の論文
2005-03-25