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Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
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Model Informed Precision Dosing of Tacrolimus in Children Following Heart Transplant

Jadon S Wagstaff1, Shaun S Kumar1, Kimberly M Molina2,3

  • 1Division of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, USA.

Journal of Clinical Pharmacology
|October 19, 2025
PubMed

Insights

A new decision support tool (DST) helps pediatric heart transplant patients reach stable tacrolimus dosing faster. This model-informed precision dosing approach improves patient care and reduces healthcare burdens.

Area of Science:

  • Pharmacology
  • Transplantation Medicine
  • Pediatric Cardiology

Background:

  • Tacrolimus is crucial post-transplant but has high variability and a narrow therapeutic window.
  • Individualized dosing is challenging in pediatric heart transplant recipients.
  • Population pharmacokinetic (popPK) models offer a precision dosing approach.

Purpose of the Study:

  • To develop and clinically implement a Bayesian forecasting decision support tool (DST) for tacrolimus dosing in pediatric heart transplant patients.
  • To evaluate the DST's ability to accelerate the time to stable therapeutic tacrolimus concentrations.
  • To assess the clinical utility of model-informed precision dosing (MIPD) in this fragile population.

Main Methods:

  • A previously developed tacrolimus popPK model was used to create a DST.
  • The DST underwent in silico testing for mathematical fidelity.
  • A clinical trial (NCT04380311) enrolled 15 pediatric heart transplant recipients (6 months–17 years) for DST-guided dosing.
  • Time to stable therapeutic tacrolimus dosing was compared to a historical cohort.

Main Results:

  • DST-guided dosing achieved stable tacrolimus levels approximately 3 days faster (6.9 days) compared to the historical cohort (9.8 days) (P = .03).
  • The DST demonstrated clinical utility despite challenges in patients on continuous renal replacement therapy.
  • This represents the first DST specifically for pediatric heart transplant recipients.

Conclusions:

  • The developed DST significantly accelerates time to stable tacrolimus dosing in pediatric heart transplant patients.
  • Model-informed precision dosing via DST offers substantial benefits for patients, clinicians, and healthcare systems.
  • This approach facilitates more rapid and effective immunosuppression management in a vulnerable pediatric population.

Keywords:
cardiac surgerydecision support toolpediatric surgerypharmacologytacrolimus

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