Binding of tacrolimus (FK506) with human plasma proteins re-evaluation and effect of mycophenolic acid
Iwasaki, K.; Miyazaki, Y.; Teramura, Y.; Kawamura, A.; Tozuka, Z.; Hata, T.; Undre, N.
Research Communications in Molecular Pathology and Pharmacology 94(3): 251-257
1996
ISSN/ISBN: 1078-0297 PMID: 9029671 Document Number: 468456
Protein binding of tacrolimus (FK506) in human plasma was re-evaluated by equilibration dialysis and compared with that of FK506 previously reported by two different methods (about 99 and 77% by an ultrafiltration and ultracentrifugation method, respectively). The binding determined in this study was about 99 % irrespective of FK506 concentrations added (0.5 - 10 ng/ml) and this value was very close to that estimated by the ultrafiltration method. The effect of mycophenolic acid (MPA, an active form of the immunosuppressant mycophenolate mofetil) and its glucuronide (MPAG, a major metabolite of mycophenolate mofetil in human plasma) on the binding was studied at concentration levels of 1 and 10 ng/ml of FK506. The binding was not affected significantly by the addition of MPA (25 - 100 mu-g/ml) and/or MPAG(100 - 1500 mu-g/ml). FK506 has already been reported not to cause significant changes of plasma protein binding of MPA. The results indicate that the unbound fraction of FK506 is about 1% in human plasma and that concomitant administration of FK506 and mycophenolic mofetil does not cause the drastic change of the binding of FK506 and MPA with human plasma proteins.