Evidence map›Paper›PMID 31646767›Full record

Trial reportCPT: pharmacometrics & systems pharmacology2019

Population Pharmacokinetic/Pharmacodynamic Modeling of Methylprednisolone in Neonates Undergoing Cardiopulmonary Bypass.

Christoph P Hornik, Daniel Gonzalez, Julie Dumond, Huali Wu, Eric M Graham, Kevin D Hill, Michael Cohen-Wolkowiez

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in CPT: pharmacometrics & systems pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.3field-weighted citation impact, top 43% 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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. A Bayesian re-analysis of the STRESS trial.American heart journal · 2026
    Trial
  2. Article
  3. Article
  4. 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

7 authors at 4 institutions in 1 country.

Christoph P HornikDuke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Daniel GonzalezDivision of Pharmacotherapy and Experimental Therapeutics, University of North Carolina Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Julie DumondDivision of Pharmacotherapy and Experimental Therapeutics, University of North Carolina Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Huali WuDuke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Eric M GrahamDepartment of Pediatrics, Medical University of South Carolina, Charleston, South Carolina, USA.
Kevin D HillDuke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Michael Cohen-WolkowiezDuke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Clinical Research Institute · USDuke University · USUniversity of North Carolina at Chapel Hill · USMedical University of South Carolina · US

Funding

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
Mentoring in Clinical Pharmacology and Early Phase TrialsK24AI143971 · NIAID · DUKE UNIVERSITY · PI COHEN-WOLKOWIEZ, MICHAEL · 2019 to 2023
$895k
Use of Physiologically-Based PK/PD Models to Streamline Drug ApprovalsK23HD083465 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI GONZALEZ, DANIEL · 2015 to 2019
$727k
Pharmacokinetics, Pharmacodynamics, and Safety of Methylprednisolone in Neonates on Cardiopulmonary BypassK23HD090239 · NICHD · DUKE UNIVERSITY · PI HORNIK, CHRISTOPH · 2017 to 2020
$646k
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) 1R01HD096435Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) 5K23HD083465FDA HHS U18 FD006298National Centers for Advancing Translational Sciences U01TR-001803-01National Institute of Allergy and Infectious Diseases HHSN272201500006INIAID NIH HHS HHSN272201300017INIAID NIH HHS K24 AI143971NICHD NIH HHS HHSN275201000003INICHD NIH HHS K23 HD083465NICHD NIH HHS K23 HD090239NIH HHS R01-HD076676
6 · The paper itself

Abstract

Methylprednisolone is used in neonates to modulate cardiopulmonary bypass (CPB)-induced inflammation, but optimal dosing and exposure are unknown. We used plasma methylprednisolone and interleukin (IL)-6 and IL-10 concentrations from neonates enrolled in a randomized trial comparing one vs. two doses of methylprednisolone to develop indirect response population pharmacokinetic/pharmacodynamic models characterizing the exposure-response relationships. We applied the models to simulate methylprednisolone dosages resulting in the desired IL-6 and -10 exposures, known mediators of CPB-induced inflammation. A total of 64 neonates (median weight 3.2 kg, range 2.2-4.3) contributed 290 plasma methylprednisolone concentrations (range 1.07-12,700 ng/mL) and IL-6 (0-681 pg/mL) and IL-10 (0.1-1125 pg/mL). Methylprednisolone plasma exposure following a single 10 mg/kg intravenous dose inhibited IL-6 and stimulated IL-10 production when compared with placebo. Higher (30 mg/kg) or more frequent (twice) dosing did not confer additional benefit. Clinical efficacy studies are needed to evaluate the effect of optimized dosing on outcomes.

Indexed as

AlgorithmsAnti-Inflammatory AgentsCardiopulmonary BypassDose-Response Relationship, DrugDrug Administration ScheduleFemaleHumansInfant, NewbornInterleukin-10Interleukin-6MaleMethylprednisoloneModels, BiologicalAnti-Inflammatory AgentsIL10 protein, humanIL6 protein, humanInterleukin-10Interleukin-6Methylprednisolone

Identifiers

PMID31646767
PMCPMC6930860
OpenAlexW2981888200

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.