*Purpose: Tacrolimus time in therapeutic range (TTR) as a measure of intra-patient variability has been associated with poor long-term outcomes. Multiple factors may contribute to TTR but few have been evaluated. The purpose of this study was to investigate the impact of CYP3A5 phenotype on TTR early post-transplant in pediatric patients.

*Methods: This was a retrospective analysis of all pediatric patients who underwent renal or heart transplant from 6/1/14 to 12/31/18 and were initiated on tacrolimus with whole blood or buffy coat samples available for secondary use. Samples were genotyped for CYP3A5*3, CYP3A5*6, and CYP3A5*7 and categorized as CYP3A5 expressers (CYP3A5*1) or CYP3A5 non-expressers. TTR was calculated for the first 90 days post-transplant using the Rosendaal linear interpolation method. Target tacrolimus levels were 8-12ng/mL in kidney recipients and 10-15 ng/mL in heart recipients. Per protocol, initial dose of tacrolimus was 0.1 mg/kg twice daily. The primary outcome compared 90-day TTR between CYP3A5 expressers and non-expressers using simple and multiple linear regression.

*Results: A total of 85 pediatric transplant patients were analyzed; 37 heart recipients and 48 kidney recipients. Nineteen patients were CYP3A5 expressers and 66 were CYP3A5 non-expressers. TTR in the first 90 days post-transplant was significantly higher among non-expressers (57.95% vs 47.29%, p=0.026; figure 1). The difference remained significant when controlling for organ type and initial dose (p= 0.029).As expected, CYP3A5 expressers required a higher dose at all evaluated timepoints (table 1). However, there was no difference in the time to the first stable, therapeutic trough defined as ≥2 sequential troughs within target (18.2 days vs 21.2 days, p=0.057; figure 2). There was also no difference when controlling for organ type and initial dose (p=0.346). A post hoc analysis of 30-day TTR also found no difference by CYP3A5 phenotype (49.1% vs 46.75%, p=0.67).

*Conclusions: CYP3A5 phenotype is associated with TTR early post-transplant beyond the known increase in time to first therapeutic level. Future work should further explore the benefit of genotype directed dosing on TTR.

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