Evidence map›Paper›PMID 30520273›Full record

ArticleCPT: pharmacometrics & systems pharmacology2019

Assessing CYP2C19 Ontogeny in Neonates and Infants Using Physiologically Based Pharmacokinetic Models: Impact of Enzyme Maturation Versus Inhibition.

Peng Duan, Fang Wu, Jason N Moore, Jeffrey Fisher, Victor Crentsil, Daniel Gonzalez, Lei Zhang, Gilbert J Burckart, Jian Wang

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

Article 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 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

9 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Ontogeny of Drug-Metabolizing Enzymes.Methods in molecular biology (Clifton, N.J.) · 2021
    Review
  8. Review
  9. 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

9 authors at 3 institutions in 1 country.

Peng DuanOffice of New Drug Product, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
Fang WuOffice of New Drug Product, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
Jason N MooreOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
Jeffrey FisherDivision of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, Arkansas, USA.
Victor CrentsilOffice of Drug Evaluation III, Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
Daniel GonzalezDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Lei ZhangOffice of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
Gilbert J BurckartOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
Jian WangOffice of Drug Evaluation IV, Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
Center for Drug Evaluation and Research · USNational Center for Toxicological Research · USUniversity of North Carolina at Chapel Hill · US

Funding

CLINICAL PHARMACOLOGY TRAINING PROGRAMT32GM008562 · NIGMS · THOMAS JEFFERSON UNIVERSITY · PI WALTER K KRAFT, Scott A. Waldman · 1995 to 2026
$10.2M
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
NICHD NIH HHS K23 HD083465NIGMS NIH HHS T32 GM008562
6 · The paper itself

Abstract

The objective of this study was to develop pediatric physiologically based pharmacokinetic (PBPK) models for pantoprazole and esomeprazole. Pediatric PBPK models were developed by Simcyp version 15 by incorporating cytochrome P450 (CYP)2C19 maturation and auto-inhibition. The predicted-to-observed pantoprazole clearance (CL) ratio ranged from 0.96-1.35 in children 1-17 years of age and 0.43-0.70 in term infants. The predicted-to-observed esomeprazole CL ratio ranged from 1.08-1.50 for children 6-17 years of age, and 0.15-0.33 for infants. The prediction was markedly improved by assuming no auto-inhibition of esomeprazole in infants in the PBPK model. Our results suggested that the CYP2C19 auto-inhibition model was appropriate for esomeprazole in adults and older children but could not be directly extended to infants. A better understanding of the complex interplay of enzyme maturation, inhibition, and compensatory mechanisms for CYP2C19 is necessary for PBPK modeling in infants.

Indexed as

Models, BiologicalAdolescentAdultChildChild, PreschoolCytochrome P-450 CYP2C19Cytochrome P-450 CYP2C19 InhibitorsEsomeprazoleHumansInfantInfant, NewbornPantoprazoleProton Pump InhibitorsCYP2C19 protein, humanCytochrome P-450 CYP2C19Cytochrome P-450 CYP2C19 InhibitorsEsomeprazolePantoprazoleProton Pump Inhibitors

Identifiers

PMID30520273
PMCPMC6430158
OpenAlexW2904000232

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.