A Comprehensive Mixed‐Method Approach to Characterize the Source of Diurnal Tacrolimus Exposure Variability in Children: Systematic Review, Meta‐analysis, and Application to an Existing Data Set.

Tacrolimus is widely reported to display diurnal variation in pharmacokinetic parameters with twice‐daily dosing. However, the contribution of chronopharmacokinetics versus food intake is unclear, with even less evidence in the pediatric population. The objectives of this study were to summarize the...

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Publicado en:Journal of Clinical Pharmacology Vol. 64; no. 3; pp. 334 - 345
Autores principales: Leino, Abbie D., Magee, John C., Kershaw, David B., Pai, Manjunath P., Park, Jeong M.
Formato: meta analysis research systematic review tables/charts Journal Article
Publicado: Wiley-Blackwell Mar2024
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Mar2024
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1002/jcph.2352
        175703936
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        atl: A Comprehensive Mixed‐Method Approach to Characterize the Source of Diurnal Tacrolimus Exposure Variability in Children: Systematic Review, Meta‐analysis, and Application to an Existing Data Set.
      aug:
        au:
          Leino, Abbie D.
          Magee, John C.
          Kershaw, David B.
          Pai, Manjunath P.
          Park, Jeong M.
        affil: Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor MI,, USA
      sug:
        subj:
          Tacrolimus Pharmacokinetics
          Circadian Rhythm
          Kidney Transplantation In Infancy and Childhood
          Food Intake
          Drug-Food Interactions Evaluation
          Human
          Child
          Meta Analysis
          Descriptive Statistics
          Systematic Review
          Confidence Intervals
          Transplant Recipients
          Tacrolimus Blood
          Metabolic Clearance Rate
          Child: 6-12 years
      ab: Tacrolimus is widely reported to display diurnal variation in pharmacokinetic parameters with twice‐daily dosing. However, the contribution of chronopharmacokinetics versus food intake is unclear, with even less evidence in the pediatric population. The objectives of this study were to summarize the existing literature by meta‐analysis and evaluate the impact of food composition on 24‐hour pharmacokinetics in pediatric kidney transplant recipients. For the meta‐analysis, 10 studies involving 253 individuals were included. The pooled effect sizes demonstrated significant differences in area under the concentration–time curve from time 0 to 12 hours (standardized mean difference [SMD], 0.27; 95% confidence interval [CI], 0.03‐0.52) and maximum concentration (SMD, 0.75; 95% CI, 0.35‐1.15) between morning and evening dose administration. However, there was significant between‐study heterogeneity that was explained by food exposure. The effect size for minimum concentration was not significantly different overall (SMD, −0.09; 95% CI, −0.27 to 0.09) or across the food exposure subgroups. A 2‐compartment model with a lag time, linear clearance, and first‐order absorption best characterized the tacrolimus pharmacokinetics in pediatric participants. As expected, adding the time of administration and food composition covariates reduced the unexplained within‐subject variability for the first‐order absorption rate constant, but only caloric composition significantly reduced variability for lag time. The available data suggest food intake is the major driver of diurnal variation in tacrolimus exposure, but the associated changes are not reflected by trough concentrations alone.
      pubtype: Academic Journal
      doctype:
        meta analysis
        research
        systematic review
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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