Evidence map›Paper›PMID 30045358›Full record

ArticleTherapeutic drug monitoring2018

Evaluation of Omeprazole Limited Sampling Strategies to Estimate Constitutive Cytochrome P450 2C19 Activity in Healthy Adults.

Swan Lin, Mina Nikanjam, Edmund V Capparelli, Alessandro Allegrini, Daniele Pavone, Dong-Seok Yim, Muhammad M Hammami, Joseph S Bertino, Anne N Nafziger, Yoo-Sin Park and 3 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Therapeutic drug monitoring, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.2field-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

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 4 countries.

Swan LinUniversity of California, San Diego, La Jolla, California.
Mina NikanjamUniversity of California, San Diego, La Jolla, California.
Edmund V CapparelliUniversity of California, San Diego, La Jolla, California.
Alessandro AllegriniFOURPHARMA C.R.O. srl, Rome, Italy.
Daniele PavoneFOURPHARMA C.R.O. srl, Rome, Italy.
Dong-Seok YimDepartment of Pharmacology, Clinical Pharmacology Unit, Clinical Trial Center/Clinical Research Institute, Seoul National University College of Medicine and Hospital, Seoul, South Korea.
Muhammad M HammamiKing Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
Joseph S BertinoBertino Consulting, Schenectady, New York.
Anne N NafzigerBertino Consulting, Schenectady, New York.
Yoo-Sin ParkShintong Rehabilitation Clinic, Suji-gu, Yongin-si, Gyeonggi-do, South Korea.
Ju-Seop KangDepartment of Pharmacology & Clinical Pharmacology Lab, College of Medicine, Hanyang University, Seoul, Republic of Korea
Ophelia Q YinSchool of Pharmacy, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
Joseph D MaUniversity of California, San Diego, La Jolla, California.
University of California San Diego · USChinese University of Hong Kong · HKKing Faisal Specialist Hospital & Research Centre · SASeoul National University Hospital · KR

Funding

Safety and Dose Optimization of High-Dose Anakinra in Kawasaki DiseaseU54HD090259 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NIGAM, SANJAY K · 2016 to 2018
$2.2M
Safety and Dose Optimization of High-Dose Anakinra in Kawasaki DiseaseP50HD090259 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NIGAM, SANJAY K · 2019 to 2020
$1.4M
NICHD NIH HHS P50 HD090259NICHD NIH HHS U54 HD090259
6 · The paper itself

Abstract

backgroundLimited sampling strategy (LSS) is a validated method to estimate pharmacokinetic (PK) parameters from a reduced number of samples. Omeprazole is used to phenotype in vivo cytochrome P450 (CYP) 2C19 activity. This study examined an LSS using 2 estimation methods to determine apparent oral clearance (CL/F) and thus CYP2C19 activity.

methodsData from 7 previously published studies included healthy subjects receiving a single, oral dose of omeprazole with intensive PK sampling. CL/F was estimated using noncompartmental analysis (NCA) and population PK modeling. LSS was simulated by selecting the 1, 2, 4, and/or 6-hour postdose time points. Linear regression was performed to assess whether CL/F estimated from limited sampling could accurately predict CL/F from the full PK profile.

resultsMedian CL/F was 23.7 L/h by NCA and 19.3 L/h by population PK modeling. In comparing the LSS NCA estimated versus observed CL/F, all evaluated linear regression models had unacceptable coefficients of determination (r, range: 0.14-0.81). With the population PK approach, 737 plasma concentrations (n = 71) and CYP2C19 genotype data were described with a 1-compartment structural model with mixed zero and first-order absorption and lag time. In comparing the population PK LSS estimated versus observed CL/F, all evaluated linear regression models had unacceptable r (range: 0.02-0.74). Post hoc comparison of CYP2C19 poor metabolizers versus CYP2C19 extensive metabolizers resulted in significantly lower CL/F in poor metabolizers versus extensive metabolizers.

conclusionsOmeprazole LSS performed poorly in estimating CL/F using 2 separate estimation approaches and does not seem to be a suitable method for determining CYP2C19 activity.

Indexed as

Sample SizeAdultAnti-Ulcer AgentsComputer SimulationCytochrome P-450 CYP2C19GenotypeHealthy VolunteersHumansModels, BiologicalOmeprazoleAnti-Ulcer AgentsCYP2C19 protein, humanCytochrome P-450 CYP2C19Omeprazole

Identifiers

PMID30045358
PMCPMC6237623
OpenAlexW2883520628

What OpenQuestion holds

Textmetadata
LicenceTDM
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.