ORAL ABSORPTION OF FK506 IN RATS

The oral absorption of FK506 in solid dispersion formulation was studi ed in rats. The obtained area under the concentration versus time curv e (AUC) increased in a nonlinear fashion with a small dose-dependent i ncrease in the peak blood concentrations (C(max)). The peak concentrat ion time (T(max)) was observed within 30 min after administration in a ll dosing groups (1-10 mg/kg) with or without feeding, whereas the ora l 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 comp aring the blood levels after infusion via the portal vein with those a fter 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 up per part of the small intestine.