Tacrolimus Dosing Between Races in Pediatric Patients Following Heart Transplant

Abstract

<h3>Purpose</h3> Limited literature is available to standardize initial pediatric tacrolimus dosing following orthotopic heart transplant (OHT), despite being a backbone of many multimodal immunosuppression regimens. There is conflicting literature regarding the impact of race, age, and weight on CYP enzyme expressions as these could contribute significantly to interpatient variability. The purpose of this research was to determine the time to therapeutic tacrolimus concentrations and significant variations in tacrolimus dose requirements between African American (AA) and Non-African American (Non-AA) pediatric OHT recipients. <h3>Methods</h3> This retrospective study evaluated tacrolimus dosing and concentrations for AA and Non-AA patients who received an OHT at Children's National Hospital. Tacrolimus dosing (mg/kg) was collected at initiation, first therapeutic concentration, and at discharge. Length of stay (LOS) following transplant was collected in both groups. <h3>Results</h3> A total of 30 patients were included in the study; n=12 AA and n=18 Non-AA. The majority of patients were between ages 7-18 years (63.3%). After tacrolimus initiation, time to achieve the first therapeutic tacrolimus concentration was similar in both groups (7 vs 6 days; p=0.36). Initial tacrolimus dosing was higher in AA population (0.07 vs 0.05 mg/kg/day; p=0.02), as was dosing when first therapeutic concentration was achieved (0.11 vs 0.06 mg/kg/day; p=0.03). Tacrolimus dosing was collected at discharge to reflect consistent therapeutic concentrations and showed higher dosing requirements in AA patients (0.14 vs 0.09 mg/kg/day; p=0.048). At the first post-operative heart catheterization, 42% of AA had rejection while 22% Non-AA had rejection; acute cellular rejection was most common (80% vs 75%). Length of hospital stay following transplant was similar in AA and Non-AA populations (20 vs 23 days; p=0.42). <h3>Conclusion</h3> African American patients required higher doses of tacrolimus at initiation, first therapeutic level, and upon discharge home. Time to therapeutic concentration was similar between both groups. Both patient populations experienced similar LOS following their transplant procedure. The majority of patients were older children, making it difficult to determine if age contributed to additional pharmacokinetic variability in tacrolimus requirements.