Evidence map›Paper›PMID 30840200›Full record

ArticleClinical pharmacokinetics2019

Physiologically Based Pharmacokinetic Modeling for Trimethoprim and Sulfamethoxazole in Children.

Elizabeth J Thompson, Huali Wu, Anil Maharaj, Andrea N Edginton, Stephen J Balevic, Marjan Cobbaert, Anthony P Cunningham, Christoph P Hornik, Michael Cohen-Wolkowiez

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical pharmacokinetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.5field-weighted citation impact, top 19% of its field
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Observational
  13. Article
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

9 authors at 2 institutions in 1 country.

Elizabeth J ThompsonDepartment of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Huali WuDuke Clinical Research Institute, 300 West Morgan Street, Suite 800, Durham, NC, 27701, USA.
Anil MaharajDuke Clinical Research Institute, 300 West Morgan Street, Suite 800, Durham, NC, 27701, USA.
Andrea N EdgintonDuke Clinical Research Institute, 300 West Morgan Street, Suite 800, Durham, NC, 27701, USA.
Stephen J BalevicDepartment of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Marjan CobbaertDuke Clinical Research Institute, 300 West Morgan Street, Suite 800, Durham, NC, 27701, USA.
Anthony P CunninghamDuke Clinical Research Institute, 300 West Morgan Street, Suite 800, Durham, NC, 27701, USA.
Christoph P HornikDepartment of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Michael Cohen-WolkowiezDepartment of Pediatrics, Duke University Medical Center, Durham, NC, USA. michael.cohenwolkowiez@duke.edu.
Clinical Research Institute · USDuke Medical Center · US

Funding

UNC-Duke Collaborative Clinical Pharmacology Postdoctoral Training Program-Evaluation SupplementT32GM086330 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KIM L.R. BROUWER, Daniel Gonzalez · 2011 to 2026
$8.5M
Physiologically-Based Pharmacokinetic Models for Optimal Drug Dosing in ChildrenR01HD076676 · NICHD · DUKE UNIVERSITY · PI COHEN-WOLKOWIEZ, MICHAEL · 2014 to 2017
$2.6M
Mentoring in Clinical Pharmacology and Early Phase TrialsK24AI143971 · NIAID · DUKE UNIVERSITY · PI COHEN-WOLKOWIEZ, MICHAEL · 2019 to 2023
$895k
FDA HHS U18 FD006298NIAID NIH HHS K24 AI143971NICHD NIH HHS R01 HD076676NIGMS NIH HHS T32 GM086330
6 · The paper itself

Abstract

objectiveThe aims of this study were to (1) determine whether opportunistically collected data can be used to develop physiologically based pharmacokinetic (PBPK) models in pediatric patients; and (2) characterize age-related maturational changes in drug disposition for the renally eliminated and hepatically metabolized antibiotic trimethoprim (TMP)-sulfamethoxazole (SMX).

methodsWe developed separate population PBPK models for TMP and SMX in children after oral administration of the combined TMP-SMX product and used sparse and opportunistically collected plasma concentration samples to validate our pediatric model. We evaluated predictability of the pediatric PBPK model based on the number of observed pediatric data out of the 90% prediction interval. We performed dosing simulations to target organ and tissue (skin) concentrations greater than the methicillin-resistant Staphylococcus aureus (MRSA) minimum inhibitory concentration (TMP 2 mg/L; SMX 9.5 mg/L) for at least 50% of the dosing interval.

resultsWe found 67-87% and 71-91% of the observed data for TMP and SMX, respectively, were captured within the 90% prediction interval across five age groups, suggesting adequate fit of our model. Our model-rederived optimal dosing of TMP at the target tissue was in the range of recommended dosing for TMP-SMX in children in all age groups by current guidelines for the treatment of MRSA.

conclusionWe successfully developed a pediatric PBPK model of the combination antibiotic TMP-SMX using sparse and opportunistic pediatric pharmacokinetic samples. This novel and efficient approach has the potential to expand the use of PBPK modeling in pediatric drug development.

Indexed as

Models, BiologicalAdolescentAdultAnti-Bacterial AgentsChildChild, PreschoolFemaleHumansInfantMaleTrimethoprim, Sulfamethoxazole Drug CombinationAnti-Bacterial AgentsTrimethoprim, Sulfamethoxazole Drug Combination

Identifiers

PMID30840200
PMCPMC6586496
OpenAlexW2922213751

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.