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 i nduced by intraperitoneal injection of cisplatin (5 mg kg(-1)) into rats. T he blood concentration of tacrolimus was measured after intravenous and int ra-intestinal administration of the drug. The blood concentration of tacrolimus after intravenous administration (1 m g kg(-1)) was slightly increased (up to 1 .3 fold) by induction of renal dy sfunction. In contrast, the peak tacrolimus concentration after intra-intes tinal administration (1 mg kg(-1) or 3 mg kg(-1)) in rats with renal failur e was about 2-fold higher than that in normal controls. The bioavailability was increased by about 35% in rats with impaired renal function as compare d with normal controls. These results suggested that the bioavailability of tacrolimus, which is mainly metabolized in the liver and intestine after o ral administration, is also influenced by renal function.