Optimal Administration of Tacrolimus in Reduced-Size Liver

Abstract

The optimal administration of immunosuppressants such as tacrolimus (Tac) for small-for-size (SFS) grafts, where the functional liver mass is small and must regenerate, has not been reported so far. The aim of this study is to clarify the characteristics of Tac metabolism according to liver volume. Seven-week-old male Wistar rats were randomly divided into three groups: (1) Tac administrated and 70% Hx group (Tac 70% Hx group), (2) Tac administrated and 90% Hx group (Tac 90% Hx group), and (3) vehicle administrated and 90% Hx group (control 90% Hx group). In both the Tac groups, Tac (0.3 mg/kg) was given daily for 3 days before operation, and daily after surgery until sacrifice (each time point; n = 5). The plasma concentration of Tac (trough level), as well as liver toxicity, were measured. The plasma concentration of Tac in the Tac 90% Hx group was significantly higher than in the Tac 70% Hx group from 24 to 72 h after operation. Furthermore, expression of CYP3AII mRNA was significantly lower in the Tac 90% Hx group than in the Tac 70% Hx group. Regarding the liver toxicity, there was no significant difference in both the Tac 90% Hx and the control 90% Hx groups. In this experimental study, the plasma concentration of Tac was dependent on the remnant liver volume. Therefore, special attention in regard to Tac administration should also be taken for patients with SFS grafts in living-donor liver transplantation (LDLT).