Change in blood tacrolimus concentration by fluctuation of renal function in a bone marrow transplant patient

The authors report a case showing a marked change in blood tacrolimus concentration due to modification of renal function in a bone marrow transplant recipient. Blood tacrolimus concentration was well controlled after transplantation, but an approximately threefold increase in the concentration was observed on day 10 even though the dosage was unchanged. Although there were no pronounced changes in hepatic enzyme activities in serum, marked elevations of renal function test values were noted; concentrations of serum creatinine (SCr) and blood urea nitrogen (BUN) were increased by more than 300% from the original levels. The tacrolimus concentration was gradually decreased by the dose reduction, but the dose-adjusted tacrolimus blood concentration (C/D) was increased contrary to the decreased tacrolimus concentration. The C/D of tacrolimus also began to decline from several days after the recovery of Scr and BUN levels and returned to the basal level. Our finding suggests that renal function has a significant effect on the pharmacokinetic disposition of tacrolimus, although this agent is almost completely eliminated by hepatic metabolism. Careful attention should be paid to alteration in tacrolimus blood concentration, especially when renal function fluctuates during post-transplant immunosuppressive therapy.