MEASUREMENT OF BLOOD-CONCENTRATIONS OF FK506 (TACROLIMUS) AND ITS METABOLITES IN 7 LIVER GRAFT PATIENTS AFTER THE FIRST DOSE BY HPLC-MS AND MICROPARTICLE ENZYME-IMMUNOASSAY (MEIA)

1 Blood and urine concentrations of the macrolide immunosuppressant FK506 and its metabolites were measured in seven orthotopic liver transplant 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 was used, allowing the measurement of parent drug and eight metabolites. Results were compared with those obtained using a microparticle enzyme immunoassay (MEIA). 2 Blood drug concentrations were described by an open two compartment model with first-order absorption giving the following 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-life was estimated at about 26 h using the h.p.l.c.-MS assay. 3 The metabolites found in blood were demethyl-FK506 and demethyl-hydroxy-FK506, while in urine FK506 and eight of its metabolites were detected.