Abstract
The oral absorption of FK506 in solid dispersion formulation was studied in rats. The obtained area under the concentration versus time curve (AUC) increased in a nonlinear fashion with a small dose-dependent increase in the peak blood concentrations (Cmax). The peak concentration time (Tmax) was observed within 30 min after administration in all dosing groups (1-10 mg/kg) with or without feeding, whereas the oral absorption of FK506 was reduced to about 50% by gavage at a dose of 1 mg/kg. Participation of first-pass elimination was suggested by comparing the blood levels after infusion via the portal vein with those after infusion via the femoral vein. Further, in an in vitro stability study and an in situ loop absorption study, FK506 was fairly stable in the gastrointestinal juice and was absorbed predominantly from the upper part of the small intestine.
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