Pharmacokinetics of three proton pump inhibitors in Chinese subjects in relation to the CYP2C19 genotype

Qiao, Huan; Hu, Yurong; Tian, Xin; Liu, Jia; Gao, Na; Zhang, Lirong; Yuzhong, Guo

doi:10.1007/s00228-005-0063-1

Cited by 42 publications

(35 citation statements)

References 28 publications

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“…This variability might be due to genetic polymorphism of the cytochrome P450 (CYP) isoform CYP2C19. [17][18][19][20] Additionally, demographic data of subjects; age, weight, height and concomitant medication could add to the high inter-individual variability.…”

Section: Discussionmentioning

confidence: 99%

Bioequivalence Studies and Pharmacokinetic Properties of Atorvastatin 40Mg Tablet in Healthy Bengali Subjects

Saha

Khan

Poddar

et al. 2017

MOJBB

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Abbreviations: t max , time to reach the maximum concentration; C max , maximum plasma concentration; t 1/2 , half-life; AUC 0-24 , area under the plasma time curve up to last quantifiable time; AUC 0-∞ , area under the plasma time curve up to time infinity; k el , elimination rate constant; NCDs, non-communicable diseases; DGDA, directorate general of drug administration; TPR, total peripheral resistance IntroductionThere is an emerging importance of bioequivalence and pharmacokinetics analysis of highly prescribed brand drugs to judge their therapeutic effectiveness, toxicity, and quality to ensure therapeutic validity and patient's safety. Statin classes of lipidlowering agents are most commonly used treatment intervention for Non-Communicable Diseases (NCDs) like diabetes, obesity, hypertension, and dyslipidemia.1 Atorvastatin is an FDA approved synthetic lipid reducing agent under statin class. This drug, also known as 2-(4-fluorophenyl) -βR, δR-dihydroxy-5-(1-methyl ethyl)-3-phenyl-4(phenylamino) carbonyl]-1H-pyrrole-1-heptanoic acid (Figure 1), is a second generation 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor.2 This synthetic HMG-CoA reductase inhibitor significantly lowers total cholesterol, low-density lipoprotein cholesterol, and plasma triglycerides in clinical studies.3 According to IMS Health, Lipitor, the pioneer brand of atorvastatin is the world's one of the biggest selling prescription medicines with cumulative sales in excess of $130 billion, but most of the principal brands are now prescribed worldwide as far cheaper generic medicines. In Bangladesh, about 50 atorvastatin brands with different strengths and dosage forms are available and their average sales volume is nearly 1.17 crore taka monthly in the national local market according to Bangladesh Directorate General of Drug Administration (DGDA). This indicates widespread prescribing of this cholesterol-lowering drug in Bangladesh. However, there is no bioequivalence data for any of existing 50 brands of atorvastatin. Dose-dependent lowering of total cholesterol, LDL cholesterol and triglyceride levels have been noticed after oral administration of atorvastatin to patients with hypercholesterolemia and to patients who have hypertriglyceridemia. 4,5 The usual starting dose is 10mg atorvastatin daily. The dose should be adjusted in accordance with plasma lipid levels and can be increased to up to 80mg daily. AbstractThe present study is aimed to investigate the single-dosing pharmacokinetics of two pharmaceutical formulations of atorvastatin 40mg tablet, test (T) sample (Stacor®) and reference (R) sample (Lipitor®) in Bengali subjects. An open-label, randomizedsequence, two-way, two-period crossover study was designed with 24 healthy Bengali male volunteers. Plasma samples collected before and over 0.5-72.0h after a single oral dose per subject. Samples were analyzed by solid phase extraction method and a validated LCMS/MS method. The non-compartmental pharmacokinetic model was used to measure pharmacokinetic parameters of peak plas...

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Section: Discussionmentioning

confidence: 99%

Bioequivalence Studies and Pharmacokinetic Properties of Atorvastatin 40Mg Tablet in Healthy Bengali Subjects

Saha

Khan

Poddar

et al. 2017

MOJBB

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“…No significant effects on PD of RPZFuruta et al [41] 18 healthy Japanese: NM = 7,IM = 7, PM = 4; LNZ 30 mg or placebo Five NM received LNZ 30 mg four times dailyAUC ratio of NM:IM:PM = 1: 2.4: 5.4 Intragastric PH in NM:IM:PM = 4.5: 4.9:5.5pH in NM after frequent administration of LNZ was 7.4 CYP2C19 significantly affects PK and PD of LNZ. NM may be at risk of lower plasma concentrations of LNZ with once-daily administration of 30 mgFuruta et al [42] 15 healthy Japanese: NM = 5,IM = 4,PM = 6; OME 20 mgAUC ratio of NM:IM:PM = 1:3.3: 12.2Intragastric pH in NM:IM:PM = 2.1: 3.3:4.5 CYP2C19 significantly affects PK and PD of OMEQiao et al [45] 18 healthy Chinese: NM = 6,IM = 6,PM = 6; randomized crossover; OME 20 mg, LNZ 30 mg or RPZ 20 mgAUC ratio of NM:IM:PMOME = 1:2.8:7.5LNZ = 1:1.7:4.0RPZ = 1:1.6:3.7 CYP2C19 significantly influences PK of the three PPIs, however with a lesser extent in RPZLeiri et al [47] 15 healthy Japanese: NM = 5,IM = 5,PM = 5; randomized crossover to once-daily dose; LNZ 30 mg or RPZ 10 mgAUC ratio of NM:IM: PMLNZ = 1:1.7:3.9RPZ = 1:1.7:3.8 CYP2C19 influenced PK of both LNZ and RPZHu YM et al [46] 20 healthy Chinese: NM = 7, IM = 6,PM = 7; single daily dose of RPZ 20 mgAUC ratio of NM:IM:PM = 1.0:1.1: 1.7No difference in median intragastric pH or percent of time pH > 4 between three phenotypes CYP2C19 influenced PK of RPZ with no significant effect on PDAdachi et al [48] 20 healthy Japanese: NM = 7,IM = 9, PM = 4; randomized crossover to RPZ 20 mg or LNZ 30 mgNighttime pH in NM:IM:PMLNZ = 1.8: 2.2: 5.9RPZ = 3.1: 4.3: 4.0Acid inhibition is significantly influenced by CYP2C19 genotype in LNZ but not RPZSahara et al [51] 40 healthy Japanese: NM = 15,IM = 15, PM = 10; randomized crossover to twice-daily; OME 20 mg, ESO 20 mg, LNZ 30 mg, RPZ 10 mgMedian pH in NM:IM:PMOME = 5.0: 5.7: 6.6LNZ = 4.7: 5.4: 6.4ESO = 5.4: 5.6: 6.2RPZ = 4.8: 5.0: 6.4Acid inhibition is significantly influenced by CYP2C19 with lesser magnitude in ESO and RPZSugimoto et al [49] 183 healthy Japanese; prospective cohort; once-daily doses; OME 20 mg, LNZ 30 mg, RPZ 10 mg;OME: NM = 16, IM = 19, PM = 15LNZ: NM = 35, IM = 21, PM = 12RPZ: NM = 23, IM = 23,PM = 19Median pH in NM:IM:PMOME = 3.8: 4.8: 5.2LNZ = 4.5: 4.8: 5.2RPZ = 4.8: 5.0:5.9…”

Section: Cyp2c19 Polymorphisms and Phenotypesmentioning

confidence: 99%

“…Similarly, the AUC following the administration of equal doses of pantoprazole in PM was sixfold higher than NM and IM [43,44]. Although reports have documented the impact of CYP2C19 genotype on PK for both rabeprazole [40,45–49] and esomeprazole [50,51], these associations with PK parameters such as AUC were of smaller magnitude than the effects reported for other PPIs, suggesting less influence of CYP2C19 genotype on these newer generations PPIs. This is not surprising given that rabepeprazole and esomeprazole are less dependent on CYP2C19 for their metabolism (Table 1).…”

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 99%

“…While an AUC ratio between PM/NM may range between 6.0 and 10 for PPIs that are extensively metabolized by CYP2C19 (omeprazole, pantoprazole and lansoprazole), this ratio is much lower (AUC PM/NM range 1.5 and 3.0) for PPIs with less CYP2C19 metabolism, such as esomeprazole and rabeprazole, respectively [45,46,50,107]. Additionally, while the CYP2C19 - inferred metabolic phenotype was consistently associated with acid suppression and therapeutic outcomes for PPIs with extensive CYP2C19 metabolism, it is not always the case with esomeprazole and rabeprazole.…”

Section: Expert Opinionsmentioning

confidence: 99%

See 1 more Smart Citation

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Rouby

Lima

Johnson

2018

Expert Opinion on Drug Metabolism & Toxicology

190

172

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Introduction: Proton Pump inhibitors (PPIs) are commonly used for a variety of acid related disorders. Despite the overall effectiveness and safety profile of PPIs, some patients do not respond adequately or develop treatment related adverse events. This variable response among patients is in part due to genotype variability of CYP2C19, the gene encoding the CYP450 (CYP2C19) isoenzyme responsible for PPIs metabolism.Areas covered: This article provides an overview of the pharmacokinetics and mechanism of action of the currently available PPIs, including the magnitude of CYPC19 contribution to their metabolism. Additionally, the role of CYP2C19 genetic variability in the therapeutic effectiveness or outcomes of PPI therapy is highlighted in details, to provide supporting evidence for the potential value of CYP2C19 genotype-guided approaches to PPI drug therapy.Expert opinion: There is a large body of evidence describing the impact of CYP2C19 variability on PPIs and its potential role in individualizing PPI therapy, yet, CYP2C19 pharmacogenetics has not been widely implemented into clinical practice. More data are needed but CYP2C19 genotype-guided dosing of PPIs is likely to become increasingly common and is expected to improve clinical outcomes, and minimize side effects related to PPIs.

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“…Considerable interindividual variability, particularly in area under the plasma concentration-time curve (AUC) data, has been described before for both intravenous and oral administration of omeprazole in children [6,7] and adults [8,9]. This high variability can be largely attributed to genetic polymorphism of the cytochrome P450 (CYP) isoform CYP2C19 [4,10]. Also, other aspects, such as age, concomitant medication and differences in weightnormalized dose, could add to the high interindividual variability.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of two formulations of omeprazole administered through a gastrostomy tube in patients with severe neurodevelopmental problems

Boussery

Smet

Cock³

et al. 2011

Brit J Clinical Pharma

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AIMS Omeprazole is often administered through a gastrostomy tube as either (i) a Multiple Unit Pellet System (MUPS (R)) tablet disintegrated in water (MUPS (R) formulation), or (ii) a suspension in 8.4% sodium bicarbonate (suspension formulation). This bioavailability study evaluates this practice in tube-fed patients with severe neurodevelopmental problems. METHODS Nonblinded, two-phase cross-over trial. RESULTS In seven of 10 patients, bioavailability was higher for the suspension formulation than for the MUPS (R) formulation. Median (90% confidence interval) area under the plasma concentration-time curve ratio (MUPS (R) over suspension) was 0.5 (0.06-2.37). CONCLUSIONS In this population, omeprazole MUPS (R) formulation has no apparent advantage over the more easily administered suspension formulation

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Pharmacokinetics of three proton pump inhibitors in Chinese subjects in relation to the CYP2C19 genotype

Cited by 42 publications

References 28 publications

Bioequivalence Studies and Pharmacokinetic Properties of Atorvastatin 40Mg Tablet in Healthy Bengali Subjects

Bioequivalence Studies and Pharmacokinetic Properties of Atorvastatin 40Mg Tablet in Healthy Bengali Subjects

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Pharmacokinetics of two formulations of omeprazole administered through a gastrostomy tube in patients with severe neurodevelopmental problems

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