The effect of CYP2C19 activity on pharmacokinetics of lansoprazole and its active metabolites in healthy subjects

Xu, Hongtao; Chen, Wei-Li; Li, Xuening; Chu, Nan-Nan

doi:10.3109/13880200903300220

Cited by 7 publications

(3 citation statements)

References 10 publications

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“…The interindividual variation of PK parameters of lansoprazole and dexlansoprazole by CYP2C19 phenotype were smaller than that of the un-phenotype group (Qiao et al, 2006 ; Xu et al, 2010 ; Li et al, 2014 ). Moreover, the interindividual variation of PK parameters by CYP2C19 phenotype after IV administration were smaller than that after oral administration.…”

Section: Discussionmentioning

confidence: 87%

Impact of Gastric H+/K+-ATPase rs2733743 on the Intragastric pH-Values of Dexlansoprazole Injection in Chinese Subjects

Sun

Cao

et al. 2017

Front. Pharmacol.

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Background: Not all patients with acid-related disorders receiving proton pump inhibitor (PP) treatment get adequate gastric pH control. The genetic variation of receptors, metabolic enzymes, and transporters are known to cause failures of therapies. We have conducted a study to evaluate the influence of gastric H+/K+-ATPase, CYP2C19, and ABCB1 polymorphisms on the pharmacokinetic and pharmacodynamic profiles of dexlansoprazole injection in healthy Chinese subjects.Methods: A total of 51 subjects were enrolled for pharmacokinetic and pharmacodynamic study after a single intravenous administration of 20 or 30 mg dexlansoprazole. Plasma concentrations were determined using a chiral liquid chromatography-mass spectrometry method. The intragastric pH and baseline-adjusted intragastric pH parameters were introduced to evaluate the pharmacodynamic characters. Genotyping was performed by polymerase chain reaction.Results: The pharmacokinetic parameters were significantly influenced by CYP2C19 phenotypes, and gastric acid secretion inhibition were affected by both gastric H+/K+-ATPase and CYP2C19 polymorphisms. Gastric H+/K+-ATPase genotypes had greater effects than CYP2C19 genotypes on the suppression of gastric acid secretion.Conclusion: Gastric H+/K+-ATPase polymorphism may be one of the main reasons that cause insufficient gastric acid inhibition.

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Section: Discussionmentioning

confidence: 87%

Impact of Gastric H+/K+-ATPase rs2733743 on the Intragastric pH-Values of Dexlansoprazole Injection in Chinese Subjects

Sun

Cao

et al. 2017

Front. Pharmacol.

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“…There are numerous studies demonstrating that genetic differences are associated with different metabolic activity of chemicals, including drugs [44][45][46]. As noted above, erlotinib is metabolized by CYP3A4, CYP1A2 and CYP1A1.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Properties of Two Erlotinib 150 mg Formulations with a Genetic Effect Evaluation in Healthy Korean Subjects

Choi

Jeon

et al. 2014

Clin Drug Investig

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This study suggests that the test and reference formulations of 150 mg erlotinib have similar pharmacokinetic characteristics. Both had no major safety issues and were well-tolerated. The test formulation met the regulatory criteria for assuming bioequivalence to the reference formulation for both AUCt and C max. The additional genetic analysis demonstrated that the major metabolic enzymes of erlotinib did not significantly affect erlotinib metabolism, with the exception of CYP1A2*1M.

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“…Plasma concentration-time data from studies where subjects received a single oral or IV administration were compiled to create a single dataset for each compound per CYP2C19 phenotype [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ]. All PK parameters and plasma concentration data were normalized to a 20 mg omeprazole dose or a 30 mg lansoprazole dose assuming dose proportionality around these doses.…”

Section: Methodsmentioning

confidence: 99%

Performance Verification of CYP2C19 Enzyme Abundance Polymorphism Settings within the Simcyp Simulator v21

et al. 2022

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Physiologically based pharmacokinetic (PBPK) modeling has a number of applications, including assessing drug–drug interactions (DDIs) in polymorphic populations, and should be iteratively refined as science progresses. The Simcyp Simulator is annually updated and version 21 included updates to hepatic and intestinal CYP2C19 enzyme abundance, including addition of intermediate and rapid metabolizer phenotypes and changes to the ultra-rapid metabolizer enzyme abundance, with implications for population clearance and DDI predictions. This work details verification of the updates with sensitive CYP2C19 substrates, omeprazole and lansoprazole, using available clinical data from literature. Multiple assessments were performed, including recovery of areas under the concentration-time curve (AUC) and Cmax from compiled datasets for each drug, recovery of victim DDI ratios with CYP2C19 and/or CYP3A4 inhibition and recovery of relative exposure between phenotypes. Simulated data were within respective acceptance criteria for >80% of omeprazole AUC values, >70% of lansoprazole AUC and Cmax, >60% of AUC and Cmax DDI ratios and >80% of exposure ratios between different phenotypes. Recovery of omeprazole Cmax was lower (>50–70% within 2-fold) and possibly attributed to the variety of formulations used in the clinical dataset. Overall, the results demonstrated that the updated data used to parameterize CYP2C19 phenotypes reasonably described the pharmacokinetics of omeprazole and lansoprazole in genotyped or phenotyped individuals.

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The effect of CYP2C19 activity on pharmacokinetics of lansoprazole and its active metabolites in healthy subjects

Abstract: (2010) The effect of CYP2C19 activity on pharmacokinetics of lansoprazole and its active metabolites in healthy subjects, Pharmaceutical Biology, 48:8,[947][948][949][950][951][952]

Cited by 7 publications

References 10 publications

Impact of Gastric H+/K+-ATPase rs2733743 on the Intragastric pH-Values of Dexlansoprazole Injection in Chinese Subjects

Impact of Gastric H+/K+-ATPase rs2733743 on the Intragastric pH-Values of Dexlansoprazole Injection in Chinese Subjects

Pharmacokinetic Properties of Two Erlotinib 150 mg Formulations with a Genetic Effect Evaluation in Healthy Korean Subjects

Performance Verification of CYP2C19 Enzyme Abundance Polymorphism Settings within the Simcyp Simulator v21

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