Evidence map›Paper›PMID 30267478›Full record

Trial reportCPT: pharmacometrics & systems pharmacology2018

Population Pharmacokinetics and Exploratory Exposure-Response Relationships of Diazepam in Children Treated for Status Epilepticus.

Lawrence C Ku, Christoph P Hornik, Ryan J Beechinor, James M Chamberlain, Jeffrey T Guptill, Barrie Harper, Edmund V Capparelli, Karen Martz, Ravinder Anand, Michael Cohen-Wolkowiez and 2 more

Open access · goldAbstract readMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in CPT: pharmacometrics & systems pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 38% 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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. 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

12 authors at 6 institutions in 1 country.

Lawrence C KuDuke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Christoph P HornikDuke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Ryan J BeechinorDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
James M ChamberlainDivision of Emergency Medicine, Children's National Medical Center, Washington, DC, USA.
Jeffrey T GuptillDuke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Barrie HarperDuke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Edmund V CapparelliSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California, USA.
Karen MartzEmmes Corporation, Rockville, Maryland, USA.
Ravinder AnandEmmes Corporation, Rockville, Maryland, USA.
Michael Cohen-WolkowiezDuke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Daniel GonzalezDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee
Clinical Research Institute · USDuke University · USEmmes (United States) · USUniversity of North Carolina at Chapel Hill · USChildren's National · USUniversity of California, San Diego · US

Funding

Duke CTSA (Composite)UL1TR001117 · NCATS · DUKE UNIVERSITY · PI BOULWARE, LEIGH E, LI, JENNIFER S · 2013 to 2017
$41.3M
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
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
NCATS NIH HHS UL1 TR001117NICHD NIH HHS HHSN275201000003CNICHD NIH HHS HHSN275201000003INICHD NIH HHS K23 HD083465NIGMS NIH HHS T32 GM086330
6 · The paper itself

Abstract

Diazepam is labeled for status epilepticus (SE) in children, but there are limited data characterizing its disposition in pediatric patients. We developed a population pharmacokinetic (PK) model of i.v. diazepam in children with SE. We evaluated relationships between PK parameters and both safety and efficacy, and simulated exposures using dosing regimens from the product label and clinical practice. The model was developed using prospective data from a pediatric clinical trial comparing diazepam to lorazepam for treatment of SE. Altogether, 87 patients aged ≥ 3 months to < 18 years contributed 162 diazepam concentrations. Diazepam PKs were well characterized by a two-compartment model scaled by body size. No significant or clinically important relationships were observed between diazepam PKs and safety or efficacy. Simulations demonstrated that, compared with label dosing, the study dose (0.2 mg/kg i.v., maximum 8 mg) resulted in greater frequency in rapidly achieving the target therapeutic range of 200-600 ng/mL.

Indexed as

Administration, IntravenousAdolescentAnticonvulsantsChildChild, PreschoolDiazepamDose-Response Relationship, DrugFemaleHumansInfantLorazepamMaleProspective StudiesStatus EpilepticusAnticonvulsantsDiazepamLorazepam

Identifiers

PMID30267478
PMCPMC6263663
OpenAlexW2893705759

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.