Evidence map›Paper›PMID 38315120›Full record

ArticleJournal of clinical pharmacology2024

Indomethacin Pharmacokinetics and Pharmacodynamics in Pregnancies With Preterm Labor: The Need for Dose-Ranging Trials.

Stephen J Balevic, Daniel Weiner, Christoph P Hornik, Michael Cohen-Wolkowiez, Daniel Gonzalez, Xiaoming Wang, Meixiang Xu, Sherif Z Abdel-Rahman, Erik Rytting

Open access · greenAbstract readMulticenter Study
In one paragraph

Article in Journal of clinical pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Current approaches and advances in placental toxicology.Trends in endocrinology and metabolism: TEM · 2026
    Review
  3. 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 3 institutions in 1 country.

Stephen J BalevicDepartment of Pediatrics, Duke University, Durham, NC, USA.ORCID 0000-0002-4016-1680
Daniel WeinerDepartment of Medicine, Duke University, Durham, NC, USA.
Christoph P HornikDepartment of Pediatrics, Duke University, Durham, NC, USA.
Michael Cohen-WolkowiezDepartment of Pediatrics, Duke University, Durham, NC, USA.
Daniel GonzalezDuke Clinical Research Institute, Duke University, Durham, NC, USA.
Xiaoming WangDepartment of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX, USA.
Meixiang XuDepartment of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX, USA.
Sherif Z Abdel-RahmanDepartment of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX, USA.
Erik RyttingDepartment of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX, USA.
Duke University · USThe University of Texas Medical Branch at Galveston · USUniversity of North Carolina at Chapel Hill · US

Funding

RADx-UP SAY YES COVID Test Study (S4)U24MD016258 · NIMHD · DUKE UNIVERSITY · PI COHEN-WOLKOWIEZ, MICHAEL, DAVE, GAURAV J · 2020 to 2023
$116.7M
Global Pediatric Clinical Trials NetworkU18FD006298 · FDA · DUKE UNIVERSITY · PI COHEN-WOLKOWIEZ, MICHAEL, HORNIK, CHRISTOPH · 2017 to 2021
$5.5M
Application of Physiologically-Based Pharmacokinetic Modeling to Characterize Drug-Drug Interactions in InfantsR01HD102949 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Daniel Gonzalez · 2021 to 2026
$3.0M
Physiologically-Based Pharmacokinetic Modeling to Guide Drug Dosing in Children with ObesityR01HD096435 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DUMOND, JULIE BRUMER · 2018 to 2022
$2.0M
Pharmacokinetic and pharmacogenomic approach to indomethacin therapy in pregnancyR01HD083003 · NICHD · UNIVERSITY OF TEXAS MED BR GALVESTON · PI RYTTING, ERIK · 2015 to 2018
$1.5M
Mentoring in Clinical Pharmacology and Early Phase TrialsK24AI143971 · NIAID · DUKE UNIVERSITY · PI COHEN-WOLKOWIEZ, MICHAEL · 2019 to 2023
$895k
Optimal Dosing for Biologic Agents in Obese Patients with Rheumatoid and Juvenile ArthritisK23AR075874 · NIAMS · DUKE UNIVERSITY · PI BALEVIC, STEPHEN JOSEPH · 2020 to 2024
$830k
Mentoring in Pediatric Cardiovascular Pharmacology and Early Phase TrialsK24HL173596 · NHLBI · DUKE UNIVERSITY · PI Christoph Hornik · 2024 to 2026
$363k
FDA HHS U18 FD006298NHLBI NIH HHS K24 HL173596NIAID NIH HHS K24 AI143971NIAMS NIH HHS K23 AR075874NICHD NIH HHS R01 HD083003NICHD NIH HHS R01 HD096435NICHD NIH HHS R01 HD102949NIMHD NIH HHS U24 MD016258
6 · The paper itself

Abstract

The use of indomethacin to delay delivery in preterm labor (PTL) is widely accepted; however, the optimal dosage of indomethacin in pregnancy is unknown. Here, we perform population pharmacokinetic (PK) and pharmacodynamic (PD) analyses, characterize the plasma disposition of indomethacin in pregnant women with PTL, and relate indomethacin exposure to delayed delivery and maternal/neonatal safety. We analyzed plasma and urine samples collected from a multicenter, prospective, opportunistic PK/PD study of indomethacin in pregnant women 12-32 weeks gestation admitted with PTL. Ninety-four participants with 639 plasma concentrations for indomethacin were included in the analysis. The final population PK (popPK) model for indomethacin was a 2-compartment structural model with first-order absorption and elimination and a covariate effect of body mass index on apparent oral clearance. We observed a 21%-60% increase in apparent oral clearance observed during pregnancy. There was no clear association between indomethacin exposure and maternal or neonatal safety outcomes, or with the magnitude of delayed delivery; however, 96.7% of women treated with indomethacin had a delivery that was delayed at least 48 hours. Given the changes to indomethacin apparent oral clearance during pregnancy, and the lack of relationship between indomethacin exposure and safety, dose-finding studies of indomethacin in pregnant women with PTL may help clarify the most safe and efficacious dosage and duration of indomethacin.

Indexed as

IndomethacinObstetric Labor, PrematureTocolytic AgentsAdultDose-Response Relationship, DrugFemaleHumansInfant, NewbornModels, BiologicalPregnancyProspective StudiesYoung AdultIndomethacinTocolytic Agentsindomethacinpharmacokineticspregnancypreterm labor

Identifiers

PMID38315120
PMCPMC11129938
OpenAlexW4391608122

What OpenQuestion holds

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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.