期刊
PHARMACOTHERAPY
卷 43, 期 7, 页码 650-658出版社
WILEY
DOI: 10.1002/phar.2836
关键词
cardiac surgery; decision support tool; pediatric surgery; pharmacology; tacrolimus
This study validated a population pharmacokinetic model for personalized dosing of the immunosuppressant tacrolimus in pediatric heart transplant patients. The model identified weight as a significant covariate and successfully predicted future tacrolimus concentrations using as few as three concentrations. These findings support the potential clinical utility of the population PK model for personalized dosing guidance.
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.
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