Evidence map›Paper›PMID 25779580›Full record

Trial reportAntimicrobial agents and chemotherapy2015

Achieving target voriconazole concentrations more accurately in children and adolescents.

Michael Neely, Ashley Margol, Xiaowei Fu, Michael van Guilder, David Bayard, Alan Schumitzky, Regina Orbach, Siyu Liu, Stan Louie, William Hope

Registry-linked trialAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01976078 (Ontogeny of Voriconazole Pharmacokinetics and Metabolism in Children and Adolescents), which is not on this map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01976078 completednot on this map

Ontogeny of Voriconazole Pharmacokinetics and Metabolism in Children and Adolescents

TypeobservationalSponsorChildren's Hospital Los AngelesRan2012 to 2015Enrolled45ConditionsPharmacokinetics, VoriconazoleArmsMidazolam/Ranitidine/Esomeprazole
3 · Its place in the literature

Who cites it

29 citing papers in PubMed.

  1. Trial
  2. Article
  3. Article
  4. RPEM: Randomized Monte Carlo parametric expectation maximization algorithm.CPT: pharmacometrics & systems pharmacology · 2024
    Article
  5. Review
  6. Review
  7. Higher Weight-Based Doses Are Required to Achieve and Maintain Therapeutic Voriconazole Serum Trough Concentrations in Children.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2023
    Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Clinical pharmacology applications in clinical drug development and clinical care: A focus on Saudi Arabia.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2020
    Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Invasive Aspergillosis in Children: Update on Current Guidelines.Mediterranean journal of hematology and infectious diseases · 2018
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Michael NeelyLaboratory of Applied Pharmacokinetics and Bioinformatics, The Saban Research Institute and the Division of Pediatric Infectious Diseases, University of Southern California Children's Hospital Los Angeles, Los Angeles, California, USA mneely@usc.edu.
Ashley MargolDivision of Pediatric Hematology/Oncology, University of Southern California Children's Hospital Los Angeles, Los Angeles, California, USA.
Xiaowei FuPathology and Laboratory Medicine, University of Southern California Children's Hospital Los Angeles, Los Angeles, California, USA.
Michael van GuilderLaboratory of Applied Pharmacokinetics and Bioinformatics, The Saban Research Institute and the Division of Pediatric Infectious Diseases, University of Southern California Children's Hospital Los Angeles, Los Angeles, California, USA.
David BayardLaboratory of Applied Pharmacokinetics and Bioinformatics, The Saban Research Institute and the Division of Pediatric Infectious Diseases, University of Southern California Children's Hospital Los Angeles, Los Angeles, California, USA.
Alan SchumitzkyLaboratory of Applied Pharmacokinetics and Bioinformatics, The Saban Research Institute and the Division of Pediatric Infectious Diseases, University of Southern California Children's Hospital Los Angeles, Los Angeles, California, USA.
Regina OrbachPharmacy Department, University of Southern California Children's Hospital Los Angeles, Los Angeles, California, USA.
Siyu LiuDepartment of Clinical Pharmacy and Pharmaceutical Economics & Policy, University of Southern California School of Pharmacy, Los Angeles, California, USA.
Stan LouieDepartment of Clinical Pharmacy and Pharmaceutical Economics & Policy, University of Southern California School of Pharmacy, Los Angeles, California, USA.
William HopeDepartment of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom.

Funding

Southern California Clinical and Translational Science InstituteUL1TR000130 · NCATS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BUCHANAN, THOMAS A · 2012 to 2015
$36.0M
Ontogeny of Voriconazole Pharmaockinetics and MetabolismR01HD070886 · NICHD · UNIVERSITY OF SOUTHERN CALIFORNIA · PI NEELY, MICHAEL N. · 2012 to 2016
$2.5M
Department of Health CS/08/08/10NCATS NIH HHS UL1 TR000130NCATS NIH HHS UL1TR000130NICHD NIH HHS R01 HD070886
6 · The paper itself

Abstract

Despite the documented benefit of voriconazole therapeutic drug monitoring, nonlinear pharmacokinetics make the timing of steady-state trough sampling and appropriate dose adjustments unpredictable by conventional methods. We developed a nonparametric population model with data from 141 previously richly sampled children and adults. We then used it in our multiple-model Bayesian adaptive control algorithm to predict measured concentrations and doses in a separate cohort of 33 pediatric patients aged 8 months to 17 years who were receiving voriconazole and enrolled in a pharmacokinetic study. Using all available samples to estimate the individual Bayesian posterior parameter values, the median percent prediction bias relative to a measured target trough concentration in the patients was 1.1% (interquartile range, -17.1 to 10%). Compared to the actual dose that resulted in the target concentration, the percent bias of the predicted dose was -0.7% (interquartile range, -7 to 20%). Using only trough concentrations to generate the Bayesian posterior parameter values, the target bias was 6.4% (interquartile range, -1.4 to 14.7%; P = 0.16 versus the full posterior parameter value) and the dose bias was -6.7% (interquartile range, -18.7 to 2.4%; P = 0.15). Use of a sample collected at an optimal time of 4 h after a dose, in addition to the trough concentration, resulted in a nonsignificantly improved target bias of 3.8% (interquartile range, -13.1 to 18%; P = 0.32) and a dose bias of -3.5% (interquartile range, -18 to 14%; P = 0.33). With the nonparametric population model and trough concentrations, our control algorithm can accurately manage voriconazole therapy in children independently of steady-state conditions, and it is generalizable to any drug with a nonparametric pharmacokinetic model. (This study has been registered at ClinicalTrials.gov under registration no. NCT01976078.).

Indexed as

AdolescentAdultAlgorithmsChildChild, PreschoolDrug MonitoringFemaleHumansInfantMaleMiddle AgedVoriconazoleYoung AdultVoriconazole

Identifiers

PMID25779580
PMCPMC4432122

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.