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. 2019 Mar-Apr;24(2):138-147.
doi: 10.5863/1551-6776-24.2.138.

Graft-to-Recipient Weight Ratio Associated With Tacrolimus Metabolism Following Pediatric Living Donor Liver Transplantations

Kensuke Shoji, Isao Miyairi, Eisuke Inoue, Akinari Fukuda, Seisuke Sakamoto, Mureo Kasahara

Graft-to-Recipient Weight Ratio Associated With Tacrolimus Metabolism Following Pediatric Living Donor Liver Transplantations

Kensuke Shoji et al. J Pediatr Pharmacol Ther. 2019 Mar-Apr.

Abstract

Objectives: Tacrolimus (TAC) is an important immunosuppressant in liver transplantation. Since TAC is mainly metabolized by the liver enzymes CYP3A4 and 5, liver function is crucial for its pharmacokinetics (PK). Liver function is dynamic after liver transplantation; hence the PK of TAC metabolism after pediatric liver transplantation is not well understood. We aimed to investigate the time-dependent changes in TAC metabolism and to find factors influencing TAC PK after pediatric liver transplantation.

Methods: We retrospectively reviewed the characteristics of the donors and recipients in pediatric living donor liver transplantation and used the TAC concentration-dose (CD) ratio as a surrogate marker of TAC metabolism.

Results: Included were 326 patients with a median age of 13 months. After the liver transplantation, the CD ratio gradually decreased, then plateaued around day 21 to 28. A linear regression analysis demonstrated that a lower graft-to-recipient weight ratio (GRWR) and higher prothrombin time-international normalized ratio (PT-INR) were independently associated with a higher CD ratio in the early period after liver transplantation. However, association between GRWR and TAC CD ratio disappeared around 6 to 12 months after a liver transplantation possibly owing to graft regeneration.

Conclusions: Tacrolimus metabolism improved within the first month after liver transplantation, and the small graft size was associated with lower TAC metabolism in the early period after pediatric living donor liver transplantation.

Keywords: children; concentration-dose ratio; immunosuppressant; liver function; tacrolimus; time-dependent change.

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Conflict of interest statement

Disclosure The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all the data and take responsibility for the integrity and accuracy of the data analysis. This study was supported by NCCHD grants 27-1 and 27-6 awarded to MK and IM, respectively.

Figures

Figure 1.
Figure 1.
Criteria for study inclusion.
Figure 2.
Figure 2.
Changes in time-dependent tacrolimus concentration-dose ratio after liver transplantation.
Figure 3.
Figure 3.
Time-dependent changes in the correlation between GRWR and the CD ratio.
Figure 4.
Figure 4.
Kaplan-Meier curve for graft loss according to the CD ratio quartile range on day 7 after liver transplantation.
See this image and copyright information in PMC

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