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MO2.3 Pediatric liver transplant recipient factors that influence tacrolimus absorption

Mary M Chandran, United States

Clinical Pharmacy Specialist
UNC Hospitals and Clinics


Pediatric liver transplant recipient factors that influence tacrolimus absorption

Mary Chandran1, Dor Yoeli2,3, Anna Sater3, Fritz Karrer2, Megan Adams2,3.

1Pharmacy, Children's Hospital Colorado, Aurora, CO, United States; 2Pediatric Surgery, Children's Hospital Colorado, Aurora, CO, United States; 3Transplant Surgery, University of Colorado, Aurora, CO, United States

Introduction: Tacrolimus (FK506) oral bioavailability in pediatric liver transplant recipients is relatively poor and highly variable. Research on recipient characteristics that influence FK506 absorption is limited. The aim of this study was to investigate the association between various recipient characteristics at time of transplant and FK506 absorption 6 months post-transplant.
Methods: All pediatric (age < 18 years) liver transplants performed at our institution between 2012 and 2020 were retrospectively reviewed. Patients were excluded for multi-organ transplant or retransplant, immunosuppression regimen not containing FK506 during first 6 months post-transplant, or patient death within 6 months of transplant. Standard immunosuppression at our institution includes FK506 and a corticosteroid taper, with or with mycophenolate mofetil per institution protocol. Target therapeutic FK506 trough levels are 10 – 12 ng/mL for post-transplant months 0 – 3, and 8 – 10 ng/mL for months 3 – 6. FK506 absorption and oral bioavailability was assessed using the Dose-Normalized Trough Concentration (DNTC), measured as the trough concentration (ng/mL) divided by the total daily dose (mg/kg/day) at 6 months post-transplant. Categorical variables are presented as n (%) and continuous variables are presented as mean (standard deviation). Association with DNTC was assessed using multivariable linear regression. Variables found to be significant (p < 0.05) upon univariable linear regression were included in the multivariable model. This study was approved by our institutional review board.
Results: 88 pediatric liver transplants were performed during the study period and met inclusion criteria. The baseline demographics of this cohort are summarized in Table 1. Upon univariable linear regression, the following variables from time of transplant were significantly associated with 6-month FK506 DNTC: age, weight, diagnosis, total bilirubin, match MELD/PELD, biliary reconstruction technique, and graft type. Weight was excluded from the multivariable model due to collinearity with age. Upon multivariable linear regression, age, total bilirubin, match MELD/PELD > 25, and living donor liver graft remained significantly and independently associated with 6-month FK506 DNTC (Table 2). Total bilirubin, match MELD/PELD, and living donor graft were positively associated with DNTC, while age was negatively associated with DNTC.

Conclusion: Novel pediatric liver transplant recipient characteristics at time of transplant associated with increased FK506 absorption 6-months post-transplant include younger age, living donor graft, MELD/PELD, and total bilirubin. These findings can help guide FK506 dosing and dose adjustments by identifying sub-groups of recipients with higher absorption and oral bioavailability.