Principle Investigator: Laura Ramsey, PhD
Transplant patients need effective immunosuppression for the transplanted organ to survive. The most common immunosuppressive agent is tacrolimus, which has a narrow therapeutic index and genetic variants that influence exposure. Genetically-guided dosing reduces some variability in exposure and can be improved upon with pharmacokinetic modeling to identify a precise dose needed to reach therapeutic exposure.
We are testing the outcomes of implementing pharmacogenetic testing and precision tacrolimus dosing in pediatric patients receiving kidney or liver transplants. Our hypothesis is that pharmacogenetically-informed precision dosing will reduce the number of dose adjustments needed to reach and remain in the therapeutic concentration range and avoid toxicity. We are enrolling 60 patients undergoing kidney or liver transplants and comparing the number of dose adjustments and incidence of toxicity between these prospectively enrolled patients and 60 matched historical controls. We anticipate that patients receiving precision dosing will achieve therapeutic range more quickly, have fewer tacrolimus dose adjustments, and may have reduced incidence of toxicity compared to historical controls. This project will enable the implementation of CYP3A5 testing through Cincinnati Children’s Genetic Pharmacology Service and provide evidence necessary to incorporate this test into routine patient care.