MEASUREMENT OF BLOOD-CONCENTRATIONS OF FK506 (TACROLIMUS) AND ITS METABOLITES IN 7 LIVER GRAFT PATIENTS AFTER THE FIRST DOSE BY HPLC-MS ANDMICROPARTICLE ENZYME-IMMUNOASSAY (MEIA)
Ak. Gonschior et al., MEASUREMENT OF BLOOD-CONCENTRATIONS OF FK506 (TACROLIMUS) AND ITS METABOLITES IN 7 LIVER GRAFT PATIENTS AFTER THE FIRST DOSE BY HPLC-MS ANDMICROPARTICLE ENZYME-IMMUNOASSAY (MEIA), British journal of clinical pharmacology, 38(6), 1994, pp. 567-571
1 Blood and urine concentrations of the macrolide immunosuppressant FK
506 and its metabolites were measured in seven orthotopic liver transp
lant patients after the first oral dose of FK506 (0.04 +/- 0.02 mg kg(
-1)) used as primary immunosuppressant. A specific h.p.l.c.-MS assay w
as used, allowing the measurement of parent drug and eight metabolites
. Results were compared with those obtained using a microparticle enzy
me immunoassay (MEIA). 2 Blood drug concentrations were described by a
n open two compartment model with first-order absorption giving the fo
llowing mean data: t(max): 1.9 (h), C-max: 17.4 (mu g l(-1)), AUC: 328
.1 (mu g l(-1) h), t(1/2,1): 0.74 (h). The terminal elimination half-l
ife was estimated at about 26 h using the h.p.l.c.-MS assay. 3 The met
abolites found in blood were demethyl-FK506 and demethyl-hydroxy-FK506
, while in urine FK506 and eight of its metabolites were detected.