PT-009 - ASSOCIATION BETWEEN TACROLIMUS AND CYP3A5 GENOTYPE IN PEDIATRIC KIDNEY TRANSPLANT.

A. Alghamdi, D. Lazear, C. Varnell, S. Seay, D. Hooper, L. Darland, T. Mizuno, L. Ramsey; Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Background: Tacrolimus (Tac), the most common immunosuppressant for organ transplant, has a narrow therapeutic range and is metabolized by CYP3A4/5. Up to 50% of the variability in Tac exposure is explained by variants in the gene CYP3A5. Given equivalent doses, CYP3A5 expressers (*1 allele carriers) demonstrate faster Tac metabolism than non-expressers. Trough concentration monitoring and dosing adjustments are used to reach a therapeutic range. Using CYP3A5-guided dosing immediately after transplant could decrease the time to the therapeutic dose and the number of dose adjustments.

Methods: We analyzed the electronic health records of 94 patients within the first 8 weeks after a kidney transplant. Banked DNA was collected and genotyping was performed for CYP3A5 *1, *3, *6, *7, and *8 alleles using the MASSArray platform. Included patients received a kidney transplant between Jan 2010 to Dec 2021, with age < 21 years at the time of the transplant. The target range was 10-15 ng/mL in the first four weeks and 7-10 ng/mL in the next four weeks.

Results: There were 1944 concentrations. We found that CYP3A5 expressers (n=22) had fewer measurements in range than non-expressers (n=72) in the first 8 weeks (32.4% vs 39.6%, p=0.045). Expressers had more dose adjustments compared to non-expressers (8.1 vs 6.7, p=0.025). The dose at a stable trough concentration was influenced by age, CYP3A5 and concomitant fluconazole (p=0.0001, p=0.02, p=0.04, respectively).

Conclusion: Using standard dosing, CYP3A5 expressers had fewer tacrolimus concentration measurements in the goal range. They require more dose adjustments and higher doses than non-expressers. Pre-emptive genotyping could decrease the number of dose changes necessary and get to a therapeutic dose faster, consistent with previous studies in adults.