Interethnic Differences in Omeprazole Metabolism in the Two S-Mephenytoin Hydroxylation Phenotypes Studied in Caucasians and Orientals

Ishizaki, Takashi; Sohn, Daewon; Kobayashi, Kaoru; Chiba, Kazuhiro; Lee, K. H.; Shin, Sang Goo; Andersson, T.; Regårdh, C G; Lou, Ya-Qing; Zhang, Y.; Dahl, Marja­‐Liisa; Bertilsson, Leif

doi:10.1097/00007691-199404000-00018

Cited by 95 publications

(70 citation statements)

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“…The proportion of individuals with the PM, hetEM and homEM genotypes in the present study were 17.4%, 39.1% and 43.5%, respectively, which was similar to previously reported percentages in the Japanese population. 25,32,33,35 The lower percentage of homEM genotypes, who degrade PPIs most rapidly, was in strong contrast to the much higher percentage (approximately 70%) observed in Caucasians. 31,36 Following separate administrations of omeprazole (20 mg/day) and rabeprazole (10 mg/day) in the present study, the median intragastric pH after the first administration initially fell following food intake but, from 4 h after dosing, began to rise for the next 11 h irrespective of the administered PPI.…”

Section: Discussionmentioning

confidence: 87%

Relationship between the Acid-Inhibitory Effects of Two Proton Pump Inhibitors and CYP2C19 Genotype in Japanese Subjects: A Randomized Two-Way Crossover Study

Furuta¹,

Adachi

Ohara³

et al. 2010

J Int Med Res

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This two-way crossover study investigated possible differences between the proton pump inhibitors, omeprazole and rabeprazole, in their effect on gastric acid secretion in Japanese subjects with differing cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) genotypes. A total of 23 Helicobacter pylorinegative healthy volunteers received omeprazole 20 mg/day and rabeprazole 10 mg/day. Each drug treatment was given for a continuous 7-day period allocated in random order, with an interval of at least 1 week between drug treatment periods to allow for wash-out. Intragastric pH was measured on days 1 and 7. Overall median intragastric pH levels at 7 and 8 h after the first administration were significantly higher with omeprazole. There was no significant difference in intragastric pH in homozygous extensive metabolizers, whereas intragastric pH was significantly higher with omeprazole in combined data from heterozygous extensive metabolizers and poor metabolizers at 6, 7 and 8 h after the first drug administration. There were no significant differences in intragastric pH between omeprazole and rabeprazole irrespective of genotype on day 7 of administration. In conclusion, on day 1 the time to onset of the antisecretory action of 20 mg/day omeprazole was more rapid than that of 10 mg/day rabeprazole in Japanese individuals who have a higher incidence of the CYP2C19 poor metabolizer genotype, however by day 7 no difference in antisecretory effect was found, regardless of genotype.

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Section: Discussionmentioning

confidence: 87%

Relationship between the Acid-Inhibitory Effects of Two Proton Pump Inhibitors and CYP2C19 Genotype in Japanese Subjects: A Randomized Two-Way Crossover Study

Furuta¹,

Adachi

Ohara³

et al. 2010

J Int Med Res

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“…Asians have a higher proportion of PM compared with Western populations, particularly Caucasians and African-Americans [139,141] . In contrast, Caucasians have a higher prevalence rate of HomEM compared with Asians [142] . Accordingly, geographic differences should be considered in selecting doses or types of PPIs for H. pylori treatment since there is a significant difference between HetEM and HomEM (OR = 1.90; 95%CI: 1.38-2.60) in H. pylori eradication rate [143] .…”

Section: Is Tailored Therapy On the Horizon For H Pylori Treatment?mentioning

confidence: 83%

Antibiotic treatment forHelicobacter pylori: Is the end coming?

Kim

Choi

Chung

2015

WJGPT

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Infection with the Gram-negative pathogen Helicobacter pylori (H. pylori ) has been associated with gastroduodenal disease and the importance of H. pylori eradication is underscored by its designation as a group I carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Core tip: This article reviews the recent literature describing antibiotic resistance and trends in Helicobacter pylori (H. pylori ) treatment. As there is no effective conventional therapy, new treatments are being developed and bismuth quadruple, sequential, concomitant therapies are recommended as a first-line regimen in regions with high levels of clarithromycin resistance. Quinolones have also been used for H. pylori treatment, although the cure rate has gradually reduced with this approach. New therapeutic directions include probiotic supplementation, tailored therapy, novel agents, and nanotechnology.

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“…clearance of omeprazole is higher in Caucasian EM Polymorphic S-mephenytoin hydroxylation [3] is compared with Korean and Chinese EM [2,9,10]. As catalysed by cytochrome P450 2C19(CYP2C19) the frequency of subjects with defective S-mepheny-(3% PM in Sweden), there is accordingly a higher frequency of heterozygous EM among Orientals compared with Caucasians [6,10].…”

Section: Introductionmentioning

confidence: 99%

Interphenotype differences in disposition and effect on gastrin levels of omeprazole—suitability of omeprazole as a probe for CYP2C19.

Chang

Tybring

et al. 1995

Brit J Clinical Pharma

173

142

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1. Fourteen healthy Swedish Caucasian subjects were given 20 mg of omeprazole orally each morning for 8 days. The subjects included five poor metabolisers (PM) of S‐mephenytoin, four heterozygous extensive metabolisers (hetEM) and five subjects with a very rapid metabolism (rapidEM). 2. After the first dose, the relative mean areas under the plasma concentration vs time curve (AUC) of omeprazole in rapidEM, hetEM and PM were 1:3.7:20 (all different, P < 0.001). A similar relation was seen in the AUC(0,10 h) of the sulphone metabolite (1:3:12). Concentrations of hydroxyomeprazole were higher in EM than in PM confirming that the hydroxy, but not the sulphone metabolite, is formed by the S‐mephenytoin hydroxylase (CYP2C19). After 8 days of treatment, the differences between groups were similar. 3. After both the first and the eighth doses, the omeprazole/hydroxyomeprazole plasma concentration ratio, determined 3 h after drug intake, correlated with the mephenytoin S/R ratio (rs = 0.94; P < 0.001; n = 14) suggesting that omeprazole might be used to phenotype for CYP2C19. 4. After the first dose of omeprazole, there was no difference in the AUC(0,10 h) of plasma gastrin between the three groups. From the first to the eighth dose, the AUC(0,10) of gastrin increased significantly in both hetEM and PM, while there was no change in the rapidEM. After the eighth dose, the AUC(0,10) of gastrin correlated significantly with the AUC of omeprazole in plasma (rs = 0.79; P < 0.01; n = 13).

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Interethnic Differences in Omeprazole Metabolism in the Two S-Mephenytoin Hydroxylation Phenotypes Studied in Caucasians and Orientals

Cited by 95 publications

References 0 publications

Relationship between the Acid-Inhibitory Effects of Two Proton Pump Inhibitors and CYP2C19 Genotype in Japanese Subjects: A Randomized Two-Way Crossover Study

Relationship between the Acid-Inhibitory Effects of Two Proton Pump Inhibitors and CYP2C19 Genotype in Japanese Subjects: A Randomized Two-Way Crossover Study

Antibiotic treatment forHelicobacter pylori: Is the end coming?

Interphenotype differences in disposition and effect on gastrin levels of omeprazole—suitability of omeprazole as a probe for CYP2C19.

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