External assessment and refinement of a population pharmacokinetic model to guide tacrolimus dosing in pediatric heart transplant.

Autor: Rower JE; Department of Pharmacology and Toxicology, University of Utah College of Pharmacy, Salt Lake City, Utah, USA.; Center for Human Toxicology, University of Utah College of Pharmacy, Salt Lake City, Utah, USA., McKnite A; Department of Pharmacology and Toxicology, University of Utah College of Pharmacy, Salt Lake City, Utah, USA., Hong B; Division of Pediatric Cardiology, University of Washington and Seattle Children's Hospital, Seattle, Washington, USA., Daly KP; Department of Pediatric Cardiology, Harvard Medical School/Boston Children's Hospital, Boston, Massachusetts, USA., Hope KD; Department of Pediatrics, Lillie Frank Abercrombie Division of Pediatric Cardiology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA., Cabrera AG; Department of Pediatrics, Lillie Frank Abercrombie Division of Pediatric Cardiology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.; Division of Pediatric Cardiology, University of Utah/Intermountain Primary Children's Hospital, Salt Lake City, Utah, USA., Molina KM; Division of Pediatric Cardiology, University of Utah/Intermountain Primary Children's Hospital, Salt Lake City, Utah, USA.
Jazyk: angličtina
Zdroj: Pharmacotherapy [Pharmacotherapy] 2023 Jul; Vol. 43 (7), pp. 650-658. Date of Electronic Publication: 2023 Jun 22.
DOI: 10.1002/phar.2836
Abstrakt: Study Objective: The immunosuppressant tacrolimus is a first-line agent to prevent graft rejection following pediatric heart transplant; however, it suffers from extensive inter-patient variability and a narrow therapeutic window. Personalized tacrolimus dosing may improve transplant outcomes by more efficiently achieving and maintaining therapeutic tacrolimus concentrations. We sought to externally validate a previously published population pharmacokinetic (PK) model that was constructed with data from a single site.
Data Source: Data were collected from Seattle, Texas, and Boston Children's Hospitals, and assessed using standard population PK modeling techniques in NONMEMv7.2.
Main Results: While the model was not successfully validated for use with external data, further covariate searching identified weight (p < 0.0001 on both volume and elimination rate) as a model-significant covariate. This refined model acceptably predicted future tacrolimus concentrations when guided by as few as three concentrations (median prediction error = 7%; median absolute prediction error = 27%).
Conclusion: These findings support the potential clinical utility of a population PK model to provide personalized tacrolimus dosing guidance.
(© 2023 Pharmacotherapy Publications, Inc.)
Databáze: MEDLINE
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