Pharmacokinetics and Bioavailability of Tacrolimus in Rats with Experimental Renal Dysfunction

The effects of renal failure on the pharmacokinetics and bioavailability of tacrolimus were investigated in rats. Experimental renal dysfunction was induced by intraperitoneal injection of cisplatin (5 mg kg−1) into rats. The blood concentration of tacrolimus was measured after intravenous and intra‐intestinal administration of the drug. The blood concentration of tacrolimus after intravenous administration (1 mg kg−1) was slightly increased (up to 1.3 fold) by induction of renal dysfunction. In contrast, the peak tacrolimus concentration after intra‐intestinal administration (1 mg kg−1 or 3 mg kg−1) in rats with renal failure was about 2‐fold higher than that in normal controls. The bioavailability was increased by about 35% in rats with impaired renal function as compared with normal controls. These results suggested that the bioavailability of tacrolimus, which is mainly metabolized in the liver and intestine after oral administration, is also influenced by renal function.