ArticleClinical pharmacokinetics2005
The effect of aging on the relationship between the cytochrome P450 2C19 genotype and omeprazole pharmacokinetics.
Article in Clinical pharmacokinetics, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 69 citations in OpenAlex.
- Hydroxylation index of omeprazole in relation to CYP2C19 polymorphism and sex in a healthy Iranian population.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2014Trial
- Omeprazole limited sampling strategies to predict area under the concentration-time curve ratios: implications for cytochrome P450 2C19 and 3A phenotyping.European journal of clinical pharmacology · 2012Trial
- Influence of CYP2C19 genotype on the pharmacokinetics of R483, a CYP2C19 substrate, in healthy subjects and type 2 diabetes patients.European journal of clinical pharmacology · 2010Trial
- Comparison of esomeprazole enteric-coated capsules vs esomeprazole magnesium in the treatment of active duodenal ulcer: a randomized, double-blind, controlled study.World journal of gastroenterology · 2008Trial
- Estimation of CYP2C19 activity by the omeprazole hydroxylation index at a single point in time after intravenous and oral administration.European journal of clinical pharmacology · 2007Trial
- Prognostic Impact ofJournal of the American Heart Association · 2024Article
- Escitalopram and Sertraline Population Pharmacokinetic Analysis in Pediatric Patients.Clinical pharmacokinetics · 2023Article
- Performance Verification of CYP2C19 Enzyme Abundance Polymorphism Settings within the Simcyp Simulator v21.Metabolites · 2022Article
- Encountering Pharmacogenetic Test Results in the Psychiatric Clinic.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2022Article
- Effects of aging on clinical outcomes in patients receiving genotype-guided P2Y12 inhibitor selection after percutaneous coronary intervention.Pharmacotherapy · 2021Article
- Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype.Journal of personalized medicine · 2021Article
- Comparative study of prophylaxis with high and low doses of voriconazole in children with malignancy.Current medical mycology · 2020Article
- Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review.Journal of clinical medicine · 2020Review
- The Role of CYP450 Drug Metabolism in Precision Cardio-Oncology.International journal of molecular sciences · 2020Review
- Genomic Variation and Pharmacokinetics in Old Age: A Quantitative Review of Age- vs. Genotype-Related Differences.Clinical pharmacology and therapeutics · 2019Review
- Pharmacogenomic Impact of CYP2C19 Variation on Clopidogrel Therapy in Precision Cardiovascular Medicine.Journal of personalized medicine · 2018Review
- Evaluating a physiologically based pharmacokinetic model for prediction of omeprazole clearance and assessing ethnic sensitivity in CYP2C19 metabolic pathway.European journal of clinical pharmacology · 2015Article
- Review
- Molecular mechanisms of genetic variation and transcriptional regulation of CYP2C19.Frontiers in genetics · 2012Article
- Systematic genetic and genomic analysis of cytochrome P450 enzyme activities in human liver.Genome research · 2010Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveThe metabolic activity of cytochrome P450 (CYP) 2C19 is genetically determined, and the pharmacokinetics of omeprazole, a substrate for CYP2C19, are dependent on the CYP2C19 genotype. However, a discrepancy between the CYP2C19 genotype and omeprazole pharmacokinetics was reported in patients with liver disease or advanced cancer. The objective of the present study was to evaluate the effect of aging on the relationship between the CYP2C19 genotype and its phenotype.
methodsTwenty-eight elderly and 23 young Japanese volunteers were enrolled after being genotyped. Each subject received a single intravenous dose of omeprazole (10 mg and 20 mg for the elderly and the young groups, respectively) and blood samples were obtained up to 6 hours after dose administration to determine the plasma concentrations of omeprazole and its metabolites, 5-hydroxyomeprazole and omeprazole sulfone. Pharmacokinetic parameters were obtained by noncompartmental analysis. Linear regression models were used to examine the joint effects of covariates such as genotype, age, etc., on the pharmacokinetic parameters, and the pharmacokinetic parameters showing statistical significance were compared by ANOVA.
resultsThere were significant differences between genotypes in the area under the plasma concentration-time curve of the young group and the elderly group. The number of mutation alleles and age were significant covariates for systemic clearance (CL), but age was the only significant covariate for volume of distribution at steady state (Vss). There were significant age- and genotype-related differences and a significant age x genotype interaction in CL (20.6+/-11.0/12.7+/-4.0/3.2+/-1.0 and 5.4+/-4.0/3.7+/-1.4/2.1+/-0.7 L/h for homozygous extensive metabolisers [EMs]/heterozygous EMs/poor metabolisers [PMs] of the young and the elderly groups, respectively). In Vss, a significant difference was found between the young and the elderly groups (219+/-115 and 107+/-44.5 mL/kg, respectively), but not between three genotypes (178+/-142, 173+/-79 and 110+/-51 mL/kg for homozygous EMs, heterozygous EMs and PMs, respectively).
conclusionThe elderly EMs showed wide variance in the in vivo CYP2C19 activity and were phenotypically closer to the elderly PMs than the young EMs were to the young PMs. Some of the elderly homozygous EMs, as well as heterozygous EMs, have a metabolic activity similar to PMs, and the CYP2C19 genotype may therefore not be as useful as phenotyping in the elderly.
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