Polymorphic hydroxylation of S-mephenytoin and omeprazole metabolism in Caucasian and Chinese subjects

Andersson, Tommy; Regårdh, C G; Lou, Ya-Qing; Zhang, Yuan; Dahl, Marja­‐Liisa; Bertilsson, Leif

doi:10.1097/00008571-199202000-00005

Cited by 162 publications

(97 citation statements)

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“…The principal enzyme implicated in the metabolism of PPIs is CYP2C19. [5][6][7] The phenotype of CYP2C19 has been classified into three groups; the rapid extensive metabolizer (EM) group, the intermediate metabolizer (IM) group and the poor metabolizer group. Each group corresponds to the homozygous extensive metabolizer (HomEM), heterozygous extensive metabolizer (HetEM) and poor metabolizer (PM) by combination of wild or mutant alleles.…”

Section: Eradication Of Helicobacter Pylori (H Pylori) Infection Ismentioning

confidence: 99%

The Influence of CYP2C19 Polymorphism on Eradication of Helicobacter pylori: A Prospective Randomized Study of Lansoprazole and Rabeprazole

Lee

Jung²,

Choi³

et al. 2010

Gut Liver

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Background/Aims: The CYP2C19 polymorphism plays an important role in the metabolism of various proton-pump inhibitors. Several trials have produced conflicting data on eradication rates of Helicobacter pylori (H. pylori) among CYP2C19 genotypes. We investigated whether the CYP2C19 genotype affects the eradication rate of H. pylori by direct comparing the effects of lansoprazole-and rabeprazole-based triple therapies. Methods: A total of 492 patients infected with H. pylori was randomly treated with either 30 mg of lansoprazole or 20 mg of rabeprazole plus 500 mg of clarithromycin and 1,000 mg of amoxicillin twice daily for 1 week. CYP2C19 genotype status was determined by a PCR-restriction-fragment-length polymorphism method. After 7 to 8 weeks, H. pylori status was evaluated by a C 13 -urea breath test. Results: Four hundred and sixty-three patients were analyzed, and the eradication rate was 75.2% in a per-protocol analysis. Eradication rates for the lansoprazole regimen (n=234) were 73.8%, 80.7%, and 85.4% in the homozygous extensive (HomEM), heterozygous extensive (HetEM), and poor metabolizers (PM) groups, respectively (p=0.303). In the case of the rabeprazole regimen (n=229), the eradication rates were 68.6%, 73.0%, and 71.9% in the HomEM, HetEM, and PM groups, respectively (p=0.795). Conclusions: The efficacies of triple therapies that include lansoprazole or rabeprazole are not affected by CYP2C19 genetic polymorphisms.

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Section: Eradication Of Helicobacter Pylori (H Pylori) Infection Ismentioning

confidence: 99%

The Influence of CYP2C19 Polymorphism on Eradication of Helicobacter pylori: A Prospective Randomized Study of Lansoprazole and Rabeprazole

Lee

Jung²,

Choi³

et al. 2010

Gut Liver

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“…Omeprazole is primarily metabolized by cytochrome P450, family 2, subfamily C, and polypeptide 19 (CYP2C19) and partially metabolized by CYP3A4 [11][12][13]. Three CYP2C19 genotypes have been identified: homozygous extensive metabolizer (homo EM), heterozygous extensive metabolizer (hetero EM) and poor metabolizer (PM) [12,13].…”

Section: Introductionmentioning

confidence: 99%

“…Three CYP2C19 genotypes have been identified: homozygous extensive metabolizer (homo EM), heterozygous extensive metabolizer (hetero EM) and poor metabolizer (PM) [12,13]. Several studies have reported that the metabolism of omeprazole is influenced by the CYP2C19 genotype, resulting in interindividual variabilities in the pharmacokinetics and pharmacodynamics of omeprazole [11][12][13]. Accordingly, the genetic polymorphism of CYP2C19 should be of clinical concern in the treatment of acid-related diseases with proton pump inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Influence of the Meal and Genotype of CYP2C19 on the Pharmacokinetics of Proton Pump Inhibitors in Healthy Japanese Subjects

Shinkai¹,

Koike²,

Shimada³

et al. 2013

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Objectives: To evaluate the influence of meals on the pharmacokinetics of omeprazole and rabeprazole and to investigate these PPIs with reference to CYP2C19 genotypes in healthy Japanese men. Methods: This was a randomized, open label, four-way crossover study. Twelve healthy Japanese male volunteers received a single oral dose of either 20 mg omeprazole or 10 mg rabeprazole, in the fasted state and after a standardized breakfast. Results: Between the administration of omeprazole in the fasted state and after breakfast, there were no significant differences in Cmax, AUC, Tmax, and half-life. Between the administration of rabeprazole in the fasted state and after breakfast, there were no significant differences in Cmax, AUC and half-life, whereas the Tmax of rabeprazole after breakfast was significantly delayed (2.8 ± 1.0 vs 5.3 ± 1.8 h, respectively; p = 0.006). PMs demonstrated the highest Cmax and AUC after drug intake under the fasting state and after breakfast, and homo EMs showed a significantly delayed Tmax. Conclusion: When a single dose of either PPI was administered, the pharmacokinetics of omeprazole was not affected by the meal, whereas the Tmax of rabeprazole after the meal was significantly delayed.

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“…In the liver, the formation of 5-hydroxyomeprazole (OH-OPZ) is mainly mediated by CYP2C19, but the formation of omeprazole sulfone (OPZ-SFN) is metabolized by CYP3A4 then to hydroxyomeprazole sulfone. OPZ has a 10-fold lower affinity for CYP3A4 (Andersson et al, 1992;1994). OPZ is most affected by CYP2C19 polymorphism of the main PPIs.…”

Section: Introductionmentioning

confidence: 99%

Relative bioavailability and pharmacokinetic comparison of two different enteric formulations of omeprazole

Liu

Shentu

et al. 2012

J. Zhejiang Univ. Sci. B

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Abstract:In order to comply with the requirements for a drug listed in China, the study was developed to compare the pharmacokinetics and relative bioavailability of two different enteric formulations of omeprazole (OPZ) in healthy Chinese subjects. A total of 32 volunteers participated in the study. Plasma concentrations were analyzed by nonstereospecific liquid chromatography/tandem mass spectrometric (LC-MS/MS) method. After administration of a single 40-mg dose of the two OPZ formulations, the comparative bioavailability was assessed by calculating individual AUC 0-t (the area under the concentration-time curve from time zero to the last measurable concentration), AUC 0-∞ (the area under the concentration-time curve extrapolated to infinity), C max (the maximum observed concentration), and T peak (the time to C max ) values of OPZ, 5-hydroxyomeprazole (OH-OPZ), and omeprazole sulfone (OPZ-SFN), respectively. The 90% confidence intervals (CIs) of AUC 0-t , AUC 0-∞ , and C max were 85

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Polymorphic hydroxylation of S-mephenytoin and omeprazole metabolism in Caucasian and Chinese subjects

Cited by 162 publications

References 0 publications

The Influence of CYP2C19 Polymorphism on Eradication of Helicobacter pylori: A Prospective Randomized Study of Lansoprazole and Rabeprazole

The Influence of CYP2C19 Polymorphism on Eradication of Helicobacter pylori: A Prospective Randomized Study of Lansoprazole and Rabeprazole

Influence of the Meal and Genotype of CYP2C19 on the Pharmacokinetics of Proton Pump Inhibitors in Healthy Japanese Subjects

Relative bioavailability and pharmacokinetic comparison of two different enteric formulations of omeprazole

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