Factorial Analysis on Individual Variability of Tacrolimus Extended- Release Formulation Pharmacokinetics in the Early Period after Renal Transplantation-Factors for AUTL/AUC Decrease
Yuki Nakamura1*, Hironori Takeuchi2, Hitoshi Iwamoto1, Tatsunori Toraishi3, Osamu Konno1, Yu Kihara1, Takayoshi Yokoyama1, Toshihiko Hirano4, Kiyoshi Okuyama3, Hiroaki Katayama2, Takashi Kawaguchi2, Sakae Nezaki1 and Shigeyuki Kawachi1
- *Corresponding Author:
- Nakamura Y
Tokyo Medical University Hachioji Medical
Center Postal address: 1163 Tatemachi
Hachioji-City, Tokyo 193-0998, Japan
Tel: +81-42-665-5611, extn. 7004
E-mail: [email protected]
Received Date: December 15, 2015; Accepted Date: January 29, 2016;Published Date: January 31, 2016
Citation: Nakamura Y, Takeuchi H, Iwamoto H, Toraishi T, Konno O, et al. (2016) Factorial Analysis on Individual Variability of Tacrolimus Extended-Release Formulation Pharmacokinetics in the Early Period after Renal Transplantation-Factors for AUTL/AUC Decrease. J Kidney 2:112. doi:10.4172/2472-1220.1000112
Copyright: © 2016 Nakamura Y, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: We have often observed that the blood trough concentration (Ct) of the once-daily, prolonged-release formulation of tacrolimus (Graceptor®; GRC) becomes unstable, and it is difficult to adjust it in the early period after transplantation. Consequently, we compared the relationships between pharmacokinetic parameters and influencing factors in a group of GRC-treated patients compared with those in a group of Prograf® (PRG)-treated patients. Methods: The study included 8 patients who were newly treated with GRC and 44 patients who were newly treated with PRG. We performed 24-hour therapeutic drug monitoring to compare the relationships between pharmacokinetic parameters, including the area under the curve (AUC), the ratio of the area under the trough level (AUTL)/AUC to indicate the relationships among AUCs, peak concentration (Cp), and Ct. The Cp/Ct values, and dose/body weight (UC/ [D/BW]) values reflected bioavailability and the influencing factors; number of days after transplantation and Dose/BW in the GRC-treated and PRG-treated patients. Results: The Cp/Ct values were higher and the AUTL/AUC and AUC corrected by dose/body weight (AUC/[D/BW]) values were lower with a low number of days after transplantation (particularly within 20 days) and a large dose than a high number of days after transplantation and a small dose in the GRC-treated patients. No such associations were observed in the PRG-treated patients. Conclusion: Care is required when using GRC as there is a tendency for Cp to increase owing to rapid absorption within 20 days after transplantation. Blood levels may be unstable and side effects may be more prevalent in some patients. Moreover, the utilization rate is low and the dose is high in such patients; therefore, unstable gastrointestinal function caused by a variety of factors may play a role in the early period after transplantation.