Three-times-daily monotherapy with tacrolimus (FK 506) in kidney transplantation

Abstract

Background: Tacrolimus (FK 506) was introduced into organ transplantation as a powerful immunosuppressive but with several adverse effects. In fact, an appropriate protocol for using this agent has not yet been established. On the basis of pharmacokinetic studies and the reports of its administration as a continuous intravenous infusion, we designed the regimen of every eight hours in order to reduce the daily dosage. Methods: Tacrolimus was given to nine patients in the Japanese FK506 study. Although it was discontinued in two patients within two months because of adverse effects and acute rejection, seven other patients tolerated the agent for a long period and received the drug three times a day. Concomitant prednisolone was gradually tapered and finally withdrawn in these patients. Results: The smaller dosage of tacrolimus led to a higher trough concentration of 14.1 ± 1.6 ng/ml in the three-times-a-day regimen compared with 12.7 ± 1.9 ng/ml in twice-a-day therapy (P < 0.01). The daily dosage of tacrolimus proved to be reducible even further. Our target trough concentration was decreased finally to < 5 ng/mL. Concomitant prednisolone was withdrawn in all of the seven patients. The course of these patients has been uneventful for a year after withdrawal of prednisolone. Conclusion: Our regimen of three-times-a-day oral administration of tacrolimus is a likely protocol for reduction of its daily dosage, which lowers its adverse effects while maintaining its immunosuppressive action at a lower trough concentration without concomitant prednisolone.