Evidence mapPaperPMID 29077992Full record

Trial reportBritish journal of clinical pharmacology2018

Population pharmacokinetics of exendin-(9-39) and clinical dose selection in patients with congenital hyperinsulinism.

Chee M Ng, Fei Tang, Steven H Seeholzer, Yixuan Zou, Diva D De León

Open access · bronzeAbstract readComparative StudyRandomized Controlled Trial
In one paragraph

Trial report in British journal of clinical pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.9field-weighted citation impact, top 24% 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

11 citing papers in PubMed, 17 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Congenital Hyperinsulinism: Diagnosis and Treatment Update.Journal of clinical research in pediatric endocrinology · 2017
    Review
  11. 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

5 authors at 2 institutions in 1 country.

Chee M NgDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA.ORCID 0000-0001-6053-9196
Fei TangDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA.
Steven H SeeholzerThe Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Yixuan ZouDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA.
Diva D De LeónThe Children's Hospital of Philadelphia, Philadelphia, PA, USA.
University of Kentucky · USChildren's Hospital of Philadelphia · US

Funding

FDA HHS R01 FD004095NCATS NIH HHS UL1 TR000003NCI NIH HHS HHSN261200800001ENIDDK NIH HHS R03 DK078535NIDDK NIH HHS R56 DK083670
6 · The paper itself

Abstract

aimsCongenital hyperinsulinism (HI) is the most common cause of persistent hypoglycaemia in infants and children. Exendin-(9-39), an inverse glucagon-like peptide 1 (GLP-1) agonist, is a novel therapeutic agent for HI that has demonstrated glucose-raising effect. We report the first population pharmacokinetic (PopPK) model of the exendin-(9-39) in patients with HI and propose the optimal dosing regimen for future clinical trials in neonates with HI.

methodsA total of 182 pharmacokinetic (PK) observations from 26 subjects in three clinical studies were included for constructing the PopPK model using first order conditional estimation (FOCE) with interaction method in nonlinear mixed-effects modelling (NONMEM). Exposure metrics (area under the curve [AUC] and maximum plasma concentration [C

resultsObserved concentration-time profiles of exendin-(9-39) were described by a linear two-compartmental PK model. Following allometric scaling of PK parameters, age and creatinine clearance did not significantly affect clearance. The calculated clearance and elimination half-life for adult subjects with median weight of 69 kg were 11.8 l h

conclusionsThis is the first study to investigate the PopPK of exendin-(9-39) in humans. The final PopPK model was successfully used with preclinical toxicology findings to propose the optimal dosing regimen of exendin-(9-39) for clinical studies in neonates with HI, allowing for a more targeted dosing approach to achieve desired glycaemic response.

Indexed as

Models, BiologicalAdolescentAdultAge FactorsAnimalsArea Under CurveChildChild, PreschoolCongenital HyperinsulinismCross-Over StudiesDogsDose-Response Relationship, DrugFemaleHalf-LifeHumansInfantexendin (9-39)Peptide Fragmentscongenital disordersmodelling and simulationNONMEMpharmacokineticspopulation analysis

Identifiers

PMID29077992
PMCPMC5809353
OpenAlexW2766312801

What Socratic holds

Textmetadata
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 Socratic graph.