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


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.
Division of Transplantation, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan. Electronic address: mita@shinshu-u.ac.jp.
A
A
Mita
Division of Transplantation, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
T
T
Ikegami
Division of Transplantation, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
Y
Y
Masuda
Department of Pharmacy, Shinshu University Hospital, Matsumoto, Japan.
Y
Y
Katsuyama
Division of Transplantation, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
Y
Y
Ohno
Division of Transplantation, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
K
K
Urata
Division of Transplantation, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
Y
Y
Nakazawa
Division of Transplantation, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
A
A
Kobayashi
Division of Transplantation, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
S
S
Miyagawa
D000284:Administration, Oral; D019540:Area Under Curve; D003692:Delayed-Action Preparations; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016031:Liver Transplantation; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage*
D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D016559:Tacrolimus