Evidence map›Paper›PMID 37226024›Full record

ArticlePharmaceutical research2023

Prediction of Omeprazole Pharmacokinetics and its Inhibition on Gastric Acid Secretion in Humans Using Physiologically Based Pharmacokinetic-Pharmacodynamic Model Characterizing CYP2C19 Polymorphisms.

Shuai Li, Lei Xie, Lu Yang, Ling Jiang, Yiting Yang, Hao Zhi, Xiaodong Liu, Hanyu Yang, Li Liu

Abstract read
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Article in Pharmaceutical research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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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.

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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.

Shuai LiCenter of Pharmacokinetics and Metabolism, School of Pharmacy, China Pharmaceutical University, Nanjing, China.
Lei XieCenter of Pharmacokinetics and Metabolism, School of Pharmacy, China Pharmaceutical University, Nanjing, China.
Lu YangCenter of Pharmacokinetics and Metabolism, School of Pharmacy, China Pharmaceutical University, Nanjing, China.
Ling JiangCenter of Pharmacokinetics and Metabolism, School of Pharmacy, China Pharmaceutical University, Nanjing, China.
Yiting YangCenter of Pharmacokinetics and Metabolism, School of Pharmacy, China Pharmaceutical University, Nanjing, China.
Hao ZhiCenter of Pharmacokinetics and Metabolism, School of Pharmacy, China Pharmaceutical University, Nanjing, China.
Xiaodong LiuCenter of Pharmacokinetics and Metabolism, School of Pharmacy, China Pharmaceutical University, Nanjing, China. xdliu@cpu.edu.cn.
Hanyu YangCenter of Pharmacokinetics and Metabolism, School of Pharmacy, China Pharmaceutical University, Nanjing, China. shenyhy@cpu.edu.cn.
Li LiuCenter of Pharmacokinetics and Metabolism, School of Pharmacy, China Pharmaceutical University, Nanjing, China. liulee@cpu.edu.cn.

Funding

Jiangsu Funding Program for Excellent Postdoctoral Talent 1412200067National Natural Science Foundation of China 82073922National Natural Science Foundation of China 82173884National Natural Science Foundation of China 82204511
6 · The paper itself

Abstract

purposeTo develop a whole physiologically based pharmacokinetic-pharmacodynamic (PBPK-PD) model to describe the pharmacokinetics and anti-gastric acid secretion of omeprazole in CYP2C19 extensive metabolizers (EMs), intermediate metabolizers (IMs), poor metabolizers (PMs) and ultrarapid metabolizers (UMs) following oral or intravenous administration.

methodsA PBPK/PD model was built using Phoenix WinNolin software. Omeprazole was mainly metabolized by CYP2C19 and CYP3A4 and the CYP2C19 polymorphism was incorporated using in vitro data. We described the PD by using a turn-over model with parameter estimates from dogs and the effect of a meal on the acid secretion was also implemented. The model predictions were compared to 53 sets of clinical data.

resultsPredictions of omeprazole plasma concentration (72.2%) and 24 h stomach pH after administration (85%) were within 0.5-2.0-fold of the observed values, indicating that the PBPK-PD model was successfully developed. Sensitivity analysis demonstrated that the contributions of the tested factors to the plasma concentration of omeprazole were V

conclusionsThe successful establishment of this PBPK-PD model highlights that pharmacokinetic and pharmacodynamic profiles of drugs can be predicted using preclinical data. The PBPK-PD model also provided a feasible alternative to empirical guidance for the recommended doses of omeprazole.

Indexed as

Aryl Hydrocarbon HydroxylasesOmeprazoleAnimalsCytochrome P-450 CYP2C19DogsGenotypeHumansPharmaceutical PreparationsPolymorphism, GeneticAryl Hydrocarbon HydroxylasesCYP2C19 protein, humanCytochrome P-450 CYP2C19OmeprazolePharmaceutical PreparationsCYP2C19 polymorphismgastric acid secretionomeprazolePBPK-PD modelturn-over model

Identifiers

PMID37226024

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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.