Optimal initial dose of orally administered once-daily extended-release tacrolimus following intravenous tacrolimus therapy after liver transplantation

Abstract

Introduction: Once-daily extended-release tacrolimus (Tac-OD) is expected to reduce non-adherence in recipients after liver transplantation (LT). The aim of this study was to determine the optimal initial dose of orally administered Tac-OD after intravenous tacrolimus (Tac-IV) therapy after LT.

Patients and methods: This prospective study included 10 adult recipients who had undergone LT at our institute. The recipients were prescribed tacrolimus by continuous intravenous administration with a steroid as initial immunosuppression therapy. Tacrolimus was converted from intravenous administration to once-daily oral intake when gastrointestinal function returned. We evaluated tacrolimus concentrations in blood 9 times a day and area under the blood concentration-time curve (AUC) during conversion. The optimal initial dose of Tac-OD was determined based on simple regression analysis between the oral dose of Tac-OD and the total dose of Tac-IV during a 24-hour period.

Results: The AUC before and after conversion showed no differences. We found that the optimal initial dose of Tac-OD was 8 times the dose of Tac-IV. There was a relationship between the AUC and the trough level. No recipients experienced acute rejection or adverse effects such as renal failure, neurotoxicity, or cardiac failure during conversion.

Conclusions: We successfully converted continuous Tac-IV to oral intake of Tac-OD by adjusting the dose using trough levels without acute rejection or adverse effects. The AUC of Tac-OD correlated with the trough level. The optimal initial dose ratio of Tac-OD after Tac-IV was 8:1.