Genotype Informed Bayesian Dosing of Tacrolimus in Solid Organ Transplant- Pharmacogenomic Implementation in Children

What this Trial Is About

This research aims to evaluate how using genotype-informed Bayesian dosing of tacrolimus affects drug levels in children who have received solid organ transplants such as kidney, liver, or heart transplants. Tacrolimus is a key immunosuppressant with a narrow therapeutic range, and individual differences in drug processing can lead to under- or over-exposure, causing rejection or toxicity. The study explores whether tailoring doses based on genetic tests and Bayesian prediction improves achieving safe and effective drug levels compared to standard weight-based dosing. Participants will receive tacrolimus orally, with initial doses guided by genetic testing for CYP3A4 and CYP3A5 gene variants and ongoing doses predicted using the NextDose platform, a tool that applies Bayesian modeling to optimize dosing. The study compares a prospective group (45 children) using genotype and Bayesian dosing over an 8-week period to a retrospective group treated with standard dosing over five years. The dosing adjustments will be assessed during this prospective period to monitor drug concentration targets. During the study, participants will have their tacrolimus blood levels measured at day 4, week 3, and week 8 after transplantation to evaluate how well drug concentrations stay within the target range. Researchers will track time to reach target levels, number of dose adjustments, safety, and feasibility of the genotype-informed approach. The total follow-up period for participants in the prospective cohort is 8 weeks, with ongoing monitoring of drug exposure and related outcomes.

Utilising Genotype Informed Bayesian Dosing of Tacrolimus in Children Post Solid Organ Transplantation.