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Yoshikazu Kinoshita - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of twice daily Rabeprazole maintenance therapy for patients with reflux esophagitis refractory to standard once daily proton pump inhibitor the japan based extend study
Journal of Gastroenterology, 2018Co-Authors: Yoshikazu Kinoshita, Mitsuhiro Fujishiro, Mototsugu Kato, Yasushi Fukushima, Hironori Masuyama, Ryo Nakata, Hisanori Abe, Shinji Kumagai, Yoshiumi Okubo, Seiichiro HojoAbstract:Rabeprazole at 10 or 20 mg twice daily (b.i.d.) has been reported to be highly effective in the treatment of proton pump inhibitor (PPI)-resistant reflux esophagitis (RE) that is refractory to the standard once-daily PPI regimen. We evaluated the efficacy and safety of Rabeprazole maintenance therapy at 10 mg once daily (q.d.) or b.i.d. for longer than 8 weeks. Patients with RE refractory to standard PPI regimens for at least 8 weeks were enrolled. They were treated with Rabeprazole at 10 or 20 mg b.i.d. for 8 weeks during the open-label treatment period. After endoscopic examination, those with confirmed healing entered the subsequent double-blind maintenance therapy. During this period, the subjects were randomized to receive Rabeprazole 10 mg q.d. (control) or 10 mg b.i.d. The primary endpoint was the endoscopic no-recurrence rate at Week 52. In total, 517 subjects entered the treatment, and 359 subjects continued on maintenance therapy. The full analysis set for central assessment included 343 subjects. The no-recurrence rate at Week 52 was significantly higher in the b.i.d. group (73.9%; p < 0.001, χ2 test) than in the q.d. group (44.8%). In particular, the b.i.d. regimen was more effective in all subgroups with Los Angeles Classification Grade B to D at treatment entry. In the maintenance treatment of PPI-resistant RE, Rabeprazole at 10 mg b.i.d. exerted a stronger recurrence-preventing effect than 10 mg q.d. over 52 weeks. No particular safety issues were noted during long-term administration. ClinicalTrials.gov number: NCT02135107.
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Long-term efficacy and safety of Rabeprazole in patients taking low-dose aspirin with a history of peptic ulcers: A phase 2/3, randomized, parallel-group, multicenter, extension clinical trial
Journal of Clinical Biochemistry and Nutrition, 2015Co-Authors: Mitsuhiro Fujishiro, Yoshikazu Kinoshita, Toshihisa Takeuchi, Kazuhide Higuchi, Mototsugu Kato, Ryuichi Iwakiri, Toshio Watanabe, Nobuyuki Sugisaki, Yasushi Okada, Hisao OgawaAbstract:A 24-week, double-blind, clinical trial of Rabeprazole for the prevention of recurrent peptic ulcers caused by low-dose aspirin (LDA) has been reported, but trials for longer than 24 weeks have not been reported. The aim of this study is to assess the long-term efficacy and safety of Rabeprazole for preventing peptic ulcer recurrence on LDA therapy. Eligible patients had a history of peptic ulcers on long-term LDA (81 or 100 mg/day) therapy. Patients with no recurrence of peptic ulcers at the end of the 24-week double-blind phase with Rabeprazole (10- or 5-mg once daily) or teprenone (50 mg three times daily) entered the extension phase. Rabeprazole doses were maintained for a maximum of 76 weeks, including the double-blind 24-week period and the extension phase period (long-term Rabeprazole 10- and 5-mg groups). Teprenone was randomly switched to Rabeprazole 10 or 5 mg for a maximum of 52 weeks in the extension phase (newly-initiated Rabeprazole 10- and 5-mg groups). The full analysis set consisted of 151 and 150 subjects in the long-term Rabeprazole 10- and 5-mg groups, respectively, and the cumulative recurrence rates of peptic ulcers were 2.2 and 3.7%, respectively. Recurrent peptic ulcers were not observed in the newly-initiated Rabeprazole 10- and 5-mg groups. No bleeding ulcers were reported. No clinically significant safety findings, including cardiovascular events, emerged. The use of long-term Rabeprazole 10- and 5-mg once daily prevents the recurrence of peptic ulcers in subjects on low-dose aspirin therapy, and both were well-tolerated.
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randomised clinical trial prevention of recurrence of peptic ulcers by Rabeprazole in patients taking low dose aspirin
Alimentary Pharmacology & Therapeutics, 2014Co-Authors: Ryuichi Iwakiri, Yoshikazu Kinoshita, Toshihisa Takeuchi, Kazuhide Higuchi, Mitsuhiro Fujishiro, Toshio Watanabe, Masako Kato, M Yamauchi, M Sanomura, H NakagawaAbstract:SummaryBackground Few studies have evaluated the effects of Rabeprazole on low-dose aspirin (LDA)-induced gastroduodenal injuries. Aim To conduct a randomised, double-blind, triple-dummy, active-controlled, multicentre trial, named the PLANETARIUM study, to assess the efficacy, dose–response relationship and safety of Rabeprazole for peptic ulcer recurrence in Japanese patients on long-term LDA therapy. Methods Eligible patients had a history of endoscopically confirmed peptic ulcers and were receiving long-term LDA (81 or 100 mg/day) therapy for cardiovascular or cerebrovascular protection. Subjects were randomly segregated into three groups receiving Rabeprazole 10 mg once daily (standard dose in Japan), Rabeprazole 5 mg once daily, or teprenone (geranylgeranylacetone; mucosal protective agent commercially available in Japan) 50 mg three times per day as an active control. The primary endpoint was recurrence of peptic ulcers over 24 weeks. Results Among 472 randomised subjects, 452 subjects (n = 151, 150, 151, respectively) constituted the full analysis set. The cumulative recurrence rates of peptic ulcers over 24 weeks in the 10- and 5-mg Rabeprazole groups were 1.4% and 2.8%, respectively, both of which were significantly lower than that in the teprenone group (21.7%). The cumulative occurrence rate of bleeding ulcers over 24 weeks in the teprenone group was 4.6%, while bleeding ulcers were not observed in the 10- or 5-mg Rabeprazole groups. Rabeprazole was well tolerated at both doses. Conclusion Rabeprazole prevents the recurrence of peptic ulcers with no evidence of a major dose–response effect in subjects on low-dose aspirin therapy.
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randomised clinical trial Rabeprazole improves symptoms in patients with functional dyspepsia in japan
Alimentary Pharmacology & Therapeutics, 2013Co-Authors: Ryuichi Iwakiri, Takahisa Furuta, Kazunari Tominaga, K Furuta, Masahiko Inamori, Hironori Masuyama, Kazunari Kanke, Akihito Nagahara, Ken Haruma, Yoshikazu KinoshitaAbstract:SummaryBackground The efficacy of proton pump inhibitors (PPIs) for treating functional dyspepsia (FD) is not well established. Aim This study, named the SAMURAI study, aimed to assess the efficacy and dose–response relationship of Rabeprazole in Japanese patients with FD in a multicentre, double-blinded, randomised, placebo-controlled trial. Methods Investigated FD was diagnosed using the Rome III criteria. Subjects who did not respond to 1 week of single-blind placebo treatment in a run-in period were randomly assigned to 8 weeks of double-blind treatment with Rabeprazole 10 mg, 20 mg, 40 mg or placebo, once daily. Dyspeptic symptoms were assessed by a dyspepsia symptom questionnaire (7-point Likert scale) and symptom diary. Results Of 392 subjects entered into the run-in period, 338 were randomly assigned. Although there was no significant difference between placebo and Rabeprazole groups in complete symptom relief for four major dyspeptic symptoms, the satisfactory symptom relief of Rabeprazole 20 mg was significantly higher than placebo according to the dyspepsia symptom questionnaire (45.3% vs. 28.2%, P = 0.027) and the symptom diary assessment (48.7% vs. 30.0%, P = 0.016). The efficacy was not influenced by syndrome type or Helicobacter pylori status. No statistically significant differences in the incidence of adverse events were seen among treatment groups. Conclusions Rabeprazole 20 mg once daily but not 10 or 40 mg significantly provides satisfactory symptom relief for functional dyspepsia (ClinicalTrials.gov, Number NCT01089543).
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randomised clinical trial a multicentre double blind placebo controlled study on the efficacy and safety of Rabeprazole 5 mg or 10 mg once daily in patients with non erosive reflux disease
Alimentary Pharmacology & Therapeutics, 2011Co-Authors: Yoshikazu Kinoshita, K Ashida, Michio HongoAbstract:Aliment Pharmacol Ther 2011; 33: 213–224 Summary Background The efficacy of Rabeprazole 5 mg/day for patients with non-erosive reflux disease (NERD) has not been reported in the literature. Aim To evaluate the efficacy of Rabeprazole 5 mg and 10 mg/day in Japanese NERD patients. The influence of baseline characteristics as well as genetic background on efficacy was also analysed. Methods Subjects were grade M (minimal changes) NERD patients. Two hundred and eighty-eight of these subjects, who were nonresponders to open label antacid therapy, entered in a 4-week, double-blind treatment (placebo, Rabeprazole 5 mg or 10 mg/day). Results Complete heartburn relief rates were 21% in placebo, 34% in Rabeprazole 5 mg and 44% in Rabeprazole 10 mg (5 mg vs. placebo P = 0.074, 10 mg vs. placebo P = 0.001). Rabeprazole 5 mg was significantly more effective than placebo in elderly patients and in patients with low heartburn frequency or without hiatal hernia. The efficacy of Rabeprazole 10 mg was not influenced by age, BMI, hiatal hernia, Helicobacter pylori infection, frequency and severity of heartburn or CYP2C19 genotypes. Conclusions Rabeprazole 5 mg was effective in a subgroup of Japanese NERD patients. Rabeprazole 10 mg provided more potent heartburn relief than 5 mg and was less fragile to baseline characteristics.
Takahisa Furuta - One of the best experts on this subject based on the ideXlab platform.
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randomised clinical trial Rabeprazole improves symptoms in patients with functional dyspepsia in japan
Alimentary Pharmacology & Therapeutics, 2013Co-Authors: Ryuichi Iwakiri, Takahisa Furuta, Kazunari Tominaga, K Furuta, Masahiko Inamori, Hironori Masuyama, Kazunari Kanke, Akihito Nagahara, Ken Haruma, Yoshikazu KinoshitaAbstract:SummaryBackground The efficacy of proton pump inhibitors (PPIs) for treating functional dyspepsia (FD) is not well established. Aim This study, named the SAMURAI study, aimed to assess the efficacy and dose–response relationship of Rabeprazole in Japanese patients with FD in a multicentre, double-blinded, randomised, placebo-controlled trial. Methods Investigated FD was diagnosed using the Rome III criteria. Subjects who did not respond to 1 week of single-blind placebo treatment in a run-in period were randomly assigned to 8 weeks of double-blind treatment with Rabeprazole 10 mg, 20 mg, 40 mg or placebo, once daily. Dyspeptic symptoms were assessed by a dyspepsia symptom questionnaire (7-point Likert scale) and symptom diary. Results Of 392 subjects entered into the run-in period, 338 were randomly assigned. Although there was no significant difference between placebo and Rabeprazole groups in complete symptom relief for four major dyspeptic symptoms, the satisfactory symptom relief of Rabeprazole 20 mg was significantly higher than placebo according to the dyspepsia symptom questionnaire (45.3% vs. 28.2%, P = 0.027) and the symptom diary assessment (48.7% vs. 30.0%, P = 0.016). The efficacy was not influenced by syndrome type or Helicobacter pylori status. No statistically significant differences in the incidence of adverse events were seen among treatment groups. Conclusions Rabeprazole 20 mg once daily but not 10 or 40 mg significantly provides satisfactory symptom relief for functional dyspepsia (ClinicalTrials.gov, Number NCT01089543).
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efficacy of Rabeprazole on heartburn symptom resolution in patients with non erosive and erosive gastro oesophageal reflux disease a multicenter study from japan
Alimentary Pharmacology & Therapeutics, 2007Co-Authors: Hiroto Miwa, Takahisa Furuta, Akihito Nagahara, Makoto Sasaki, Tomoyuki Koike, Yasuki Habu, Masanori Ito, Yasuhiro Fujiwara, Tsuneya Wada, Michio HongoAbstract:Summary Background Few studies have compared the efficacy of proton pump inhibitors in resolving the symptoms of non-erosive reflux disease (NERD) and of erosive gastro-oesophageal reflux disease (GERD) in Japan. Aim To investigate and compare the efficacy of 4-week course of Rabeprazole 10 mg/day on symptom resolution in NERD and erosive GERD in Japan. Methods The modified Los Angeles classification was used to grade endoscopically GERD in patients with heartburn (Grades N and M: NERD, Grades A and B: mild reflux oesophagitis (RO), and Grades C and D: severe RO). Rabeprazole 10 mg/day was administered for 4 weeks to 180 patients who kept symptom diaries. Results Complete relief of the symptoms was achieved in 35.8% of the NERD group and 55.4% of the erosive GERD group (mild RO: 51.1% and severe RO: 77.8%). Rabeprazole was significantly more effective in erosive GERD than in NERD patients. Among the NERD subgroups (Grades N and M), no difference in symptom improvement was observed. Conclusions Four-week, Rabeprazole 10 mg/day acid suppression therapy was effective in resolving symptoms in Japanese GERD patients. This therapy was more effective in erosive GERD than in NERD patients, and in those with severe RO than in those with mild RO.
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comparison of an increased dosage regimen of Rabeprazole versus a concomitant dosage regimen of famotidine with Rabeprazole for nocturnal gastric acid inhibition in relation to cytochrome p450 2c19 genotypes
Clinical Pharmacology & Therapeutics, 2005Co-Authors: Takahisa Furuta, Naohito Shirai, Masayoshi Kajimura, Mitsushige Sugimoto, Akiko NakamuraAbstract:Background and objective A concomitant dosage regimen of a histamine 2 receptor antagonist with a proton pump inhibitor (PPI) effectively decreases the incidence of nocturnal acid breakthrough, which is one of the problems encountered when acid-related diseases are treated with a PPI alone. We compared the effectiveness of an increased dosage regimen of Rabeprazole with that of a concomitant dosage regimen of Rabeprazole with famotidine, relative to cytochrome P450 (CYP) 2C19 genotype status, on nocturnal acid inhibition. Methods Fifteen Helicobacter pylori–negative volunteers, consisting of 5 homozygous extensive metabolizers (EMs), 6 heterozygous EMs, and 4 poor metabolizers (PMs) of CYP2C19, took 20 mg Rabeprazole, 40 mg Rabeprazole, and 20 mg Rabeprazole plus 20 mg famotidine at bedtime (at 10 PM) for 8 days. The subjects then underwent 24-hour intragastric pH monitoring on day 8. Results For the 20-mg Rabeprazole, 40-mg Rabeprazole, and concomitant dosage regimens, the median percent times and ranges when nocturnal intragastric pH values were lower than 4.0 were 78.8% (47.5%-98.0%), 45.3% (29.0%-52.2%), and 15.5% (0.0%-40.8%), respectively, for homozygous EMs; 51.0% (7.0%-91.6%), 41.3% (33.0%-59.0%), and 18.5% (8.4%-31.9%), respectively, for heterozygous EMs; and 4.5% (2.0%-31.2%), 9.5% (0.0%-31.1%), and 9.3% (0.0%-14.7%), respectively, for PMs. Although significant differences in acid inhibition between the different CYP2C19 genotypes were observed when Rabeprazole alone was given (P = .016 for 20 mg Rabeprazole and P = .023 for 40 mg Rabeprazole), such differences were not observed when famotidine was concomitantly given (P = .206). Conclusions The combination regimen of famotidine plus Rabeprazole is more effective for nocturnal acid inhibition in homozygous and heterozygous EMs than the increased dosage regimen of Rabeprazole. This concomitant therapy could be a rescue regimen for patients with nocturnal acid breakthrough refractory to a standard PPI therapy who are likely to be CYP2C19 EMs. Clinical Pharmacology & Therapeutics (2005) 77, 302–311; doi: 10.1016/j.clpt.2004.10.010
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different dosage regimens of Rabeprazole for nocturnal gastric acid inhibition in relation to cytochrome p450 2c19 genotype status
Clinical Pharmacology & Therapeutics, 2004Co-Authors: Takahisa Furuta, Naohito Shirai, Masayoshi Kajimura, Mitsushige Sugimoto, Akira HishidaAbstract:Objective For the treatment of gastroesophageal reflux disease, intragastric pH should be lower than 4.0 for no more than 4 hours a day (<16.7%). We aimed to develop optimal dosage regimens for Rabeprazole to control nocturnal acidity in relation to cytochrome P450 (CYP) 2C19 genotypes. Methods Fifteen Helicobacter pylori–negative volunteers, comprising 5 homozygous extensive metabolizers (EMs), 6 heterozygous EMs, and 4 poor metabolizers (PMs) of CYP2C19, took placebo and Rabeprazole, at a dose of 20 or 40 mg once daily (at 10 PM) for 8 days. Plasma Rabeprazole concentrations and 24-hour intragastric pH were determined on days 7 and 8, respectively. Because the nocturnal intragastric pH was lower than 4.0 for more than 16.7% of the time with once-daily regimens in homozygous EMs and heterozygous EMs, they were administered 20 mg Rabeprazole twice daily (8 AM and 10 PM) or 10 mg Rabeprazole 4 times daily (8 AM, 12:30 PM, 6 PM, and 10 PM). Results With 40 mg Rabeprazole once daily, the median percent time with nocturnal pH lower than 4.0 was less than 16.7% in PMs (9.5% [range, 3.0%-31.1%]) but not in homozygous EMs (45.3% [range, 29.0%-52.2%]) (P = .043) and heterozygous EMs (41.3% [range, 33.0%-59.0%]) (P = .043). The mean plasma Rabeprazole concentrations differed among the different CYP2C19 genotype groups. With 20 mg Rabeprazole twice daily and 10 mg Rabeprazole 4 times daily, the median percent times with nocturnal pH lower than 4.0 were 5.0% (range, 0.0%-42.0%) and 1.0% (range, 5.0%-7.1%) in heterozygous EMs and 62.0% (range, 10.8%-68.3%) and 14.7% (range, 0.0%-41.7%) in homozygous EMs, respectively, and plasma concentrations were sustained longer than with the once-daily regimens. Conclusions We propose that Rabeprazole dosage regimens for sufficient acid inhibition are 20 mg once daily for PMs, 20 mg twice daily for heterozygous EMs, and 10 mg 4 times daily for homozygous EMs or heterozygous EMs. Clinical Pharmacology & Therapeutics (2004) 76, 290–301; doi: 10.1016/j.clpt.2004.06.008
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effects of cyp2c19 genotypic differences in the metabolism of omeprazole and Rabeprazole on intragastric ph
Alimentary Pharmacology & Therapeutics, 2001Co-Authors: Naohito Shirai, Takahisa Furuta, Y Moriyama, H Okochi, Kaoru Kobayashi, Misako Takashima, Fang Xiao, Kazuhiro Kosuge, Kazuko Nakagawa, Hiroyuki HanaiAbstract:Background: Omeprazole is mainly metabolized in the liver by CYP2C19, a genetically determined enzyme, whereas Rabeprazole is mainly reduced non-enzymatically and partially metabolized by CYP2C19. The therapeutic effects of Rabeprazole are therefore assumed to be less affected by an individual’s CYP2C19 status. Aim: To investigate the acid inhibitory effects and plasma levels of omeprazole and Rabeprazole with reference to different CYP2C19 genotypes. Methods: Fifteen healthy volunteers took a daily dose of 20 mg of omeprazole or Rabeprazole for 8 days. On post-dose days 1 and 8, 24-h profiles of intragastric pH were recorded and plasma concentrations of omeprazole, Rabeprazole and their metabolites were determined. Results: After single and repeated doses of omeprazole, the intragastric pH values and plasma concentrations of omeprazole and its metabolites were significantly dependent on the CYP2C19 genotype. Significant differences in the same kinetic and dynamic parameters were also observed after single doses of Rabeprazole. Although the plasma levels of Rabeprazole differed among the different CYP2C19 genotype groups after repeated doses, no significant differences in intragastric pH values were observed. Conclusions: The acid inhibitory effects of omeprazole and Rabeprazole are significantly dependent on the CYP2C19 genotype status, as well as on their intrinsic pharmacokinetic and pharmacodynamic characteristics and dosing schemes.
Mitsushige Sugimoto - One of the best experts on this subject based on the ideXlab platform.
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twice daily dosing of esomeprazole effectively inhibits acid secretion in cyp2c19 rapid metabolisers compared with twice daily omeprazole Rabeprazole or lansoprazole
Alimentary Pharmacology & Therapeutics, 2013Co-Authors: Shu Sahara, Mitsushige Sugimoto, Takahiro Uotani, Hitomi Ichikawa, Mihoko Yamade, Moriya Iwaizumi, Takanori Yamada, Satoshi Osawa, Ken Sugimoto, Kazuo UmemuraAbstract:Summary Background Twice-daily dosing of proton pump inhibitors (PPIs) is used to treat Helicobacter pylori or acid-related diseases, such as gastro-oesophageal reflux disease (GERD) refractory to standard dose of a PPI. Genetic polymorphisms of CYP2C19 are involved to different extents in the metabolism of four kinds of PPIs (omeprazole, lansoprazole, Rabeprazole and esomeprazole) available in Japan. Aim To compare acid-inhibitory effects of the four PPIs dosed twice daily in relation to CYP2C19 genotype. Methods We performed 24-h pH monitoring studies on Day 7 of PPI treatment for 40 Japanese H. pylori-negative volunteers [15 CYP2C19 rapid metabolisers (RMs), 15 intermediate metabolisers (IMs) and 10 poor metabolisers (PMs)] using a randomised four-way crossover design: omeprazole 20 mg, esomeprazole 20 mg, lansoprazole 30 mg and Rabeprazole 10 mg twice daily. Results Although median pH values with esomeprazole, omeprazole, lansoprazole and Rabeprazole were 5.7 (3.5–7.2), 5.5 (2.4–7.2), 5.5 (3.7–7.3) and 5.2 (2.5–7.3), respectively (no statistically significant differences), CYP2C19 genotype-dependent differences were smaller for esomeprazole and Rabeprazole compared with values for omeprazole and lansoprazole. In CYP2C19 RMs, the median pH with esomeprazole [5.4 (3.5–6.8)] was significantly higher than those with omeprazole [5.0 (2.4–5.9), P = 0.018], lansoprazole [4.7 (3.7-5.5), P = 0.017] or Rabeprazole [4.8 (2.5–6.4), P = 0.002]. In IMs and PMs, the median pH was >5.0 independent of the PPI. Conclusions In intermediate and rapid metabolisers of CYP2C19, PPIs dosed twice daily could attain sufficient acid suppression, while in CYP2C19 RMs, esomeprazole 20 mg twice daily caused the strongest inhibition of the four PPIs. Therefore, esomeprazole may be effective in Japanese population when dosed twice daily.
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comparison of an increased dosage regimen of Rabeprazole versus a concomitant dosage regimen of famotidine with Rabeprazole for nocturnal gastric acid inhibition in relation to cytochrome p450 2c19 genotypes
Clinical Pharmacology & Therapeutics, 2005Co-Authors: Takahisa Furuta, Naohito Shirai, Masayoshi Kajimura, Mitsushige Sugimoto, Akiko NakamuraAbstract:Background and objective A concomitant dosage regimen of a histamine 2 receptor antagonist with a proton pump inhibitor (PPI) effectively decreases the incidence of nocturnal acid breakthrough, which is one of the problems encountered when acid-related diseases are treated with a PPI alone. We compared the effectiveness of an increased dosage regimen of Rabeprazole with that of a concomitant dosage regimen of Rabeprazole with famotidine, relative to cytochrome P450 (CYP) 2C19 genotype status, on nocturnal acid inhibition. Methods Fifteen Helicobacter pylori–negative volunteers, consisting of 5 homozygous extensive metabolizers (EMs), 6 heterozygous EMs, and 4 poor metabolizers (PMs) of CYP2C19, took 20 mg Rabeprazole, 40 mg Rabeprazole, and 20 mg Rabeprazole plus 20 mg famotidine at bedtime (at 10 PM) for 8 days. The subjects then underwent 24-hour intragastric pH monitoring on day 8. Results For the 20-mg Rabeprazole, 40-mg Rabeprazole, and concomitant dosage regimens, the median percent times and ranges when nocturnal intragastric pH values were lower than 4.0 were 78.8% (47.5%-98.0%), 45.3% (29.0%-52.2%), and 15.5% (0.0%-40.8%), respectively, for homozygous EMs; 51.0% (7.0%-91.6%), 41.3% (33.0%-59.0%), and 18.5% (8.4%-31.9%), respectively, for heterozygous EMs; and 4.5% (2.0%-31.2%), 9.5% (0.0%-31.1%), and 9.3% (0.0%-14.7%), respectively, for PMs. Although significant differences in acid inhibition between the different CYP2C19 genotypes were observed when Rabeprazole alone was given (P = .016 for 20 mg Rabeprazole and P = .023 for 40 mg Rabeprazole), such differences were not observed when famotidine was concomitantly given (P = .206). Conclusions The combination regimen of famotidine plus Rabeprazole is more effective for nocturnal acid inhibition in homozygous and heterozygous EMs than the increased dosage regimen of Rabeprazole. This concomitant therapy could be a rescue regimen for patients with nocturnal acid breakthrough refractory to a standard PPI therapy who are likely to be CYP2C19 EMs. Clinical Pharmacology & Therapeutics (2005) 77, 302–311; doi: 10.1016/j.clpt.2004.10.010
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different dosage regimens of Rabeprazole for nocturnal gastric acid inhibition in relation to cytochrome p450 2c19 genotype status
Clinical Pharmacology & Therapeutics, 2004Co-Authors: Takahisa Furuta, Naohito Shirai, Masayoshi Kajimura, Mitsushige Sugimoto, Akira HishidaAbstract:Objective For the treatment of gastroesophageal reflux disease, intragastric pH should be lower than 4.0 for no more than 4 hours a day (<16.7%). We aimed to develop optimal dosage regimens for Rabeprazole to control nocturnal acidity in relation to cytochrome P450 (CYP) 2C19 genotypes. Methods Fifteen Helicobacter pylori–negative volunteers, comprising 5 homozygous extensive metabolizers (EMs), 6 heterozygous EMs, and 4 poor metabolizers (PMs) of CYP2C19, took placebo and Rabeprazole, at a dose of 20 or 40 mg once daily (at 10 PM) for 8 days. Plasma Rabeprazole concentrations and 24-hour intragastric pH were determined on days 7 and 8, respectively. Because the nocturnal intragastric pH was lower than 4.0 for more than 16.7% of the time with once-daily regimens in homozygous EMs and heterozygous EMs, they were administered 20 mg Rabeprazole twice daily (8 AM and 10 PM) or 10 mg Rabeprazole 4 times daily (8 AM, 12:30 PM, 6 PM, and 10 PM). Results With 40 mg Rabeprazole once daily, the median percent time with nocturnal pH lower than 4.0 was less than 16.7% in PMs (9.5% [range, 3.0%-31.1%]) but not in homozygous EMs (45.3% [range, 29.0%-52.2%]) (P = .043) and heterozygous EMs (41.3% [range, 33.0%-59.0%]) (P = .043). The mean plasma Rabeprazole concentrations differed among the different CYP2C19 genotype groups. With 20 mg Rabeprazole twice daily and 10 mg Rabeprazole 4 times daily, the median percent times with nocturnal pH lower than 4.0 were 5.0% (range, 0.0%-42.0%) and 1.0% (range, 5.0%-7.1%) in heterozygous EMs and 62.0% (range, 10.8%-68.3%) and 14.7% (range, 0.0%-41.7%) in homozygous EMs, respectively, and plasma concentrations were sustained longer than with the once-daily regimens. Conclusions We propose that Rabeprazole dosage regimens for sufficient acid inhibition are 20 mg once daily for PMs, 20 mg twice daily for heterozygous EMs, and 10 mg 4 times daily for homozygous EMs or heterozygous EMs. Clinical Pharmacology & Therapeutics (2004) 76, 290–301; doi: 10.1016/j.clpt.2004.06.008
Masayoshi Kajimura - One of the best experts on this subject based on the ideXlab platform.
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comparison of an increased dosage regimen of Rabeprazole versus a concomitant dosage regimen of famotidine with Rabeprazole for nocturnal gastric acid inhibition in relation to cytochrome p450 2c19 genotypes
Clinical Pharmacology & Therapeutics, 2005Co-Authors: Takahisa Furuta, Naohito Shirai, Masayoshi Kajimura, Mitsushige Sugimoto, Akiko NakamuraAbstract:Background and objective A concomitant dosage regimen of a histamine 2 receptor antagonist with a proton pump inhibitor (PPI) effectively decreases the incidence of nocturnal acid breakthrough, which is one of the problems encountered when acid-related diseases are treated with a PPI alone. We compared the effectiveness of an increased dosage regimen of Rabeprazole with that of a concomitant dosage regimen of Rabeprazole with famotidine, relative to cytochrome P450 (CYP) 2C19 genotype status, on nocturnal acid inhibition. Methods Fifteen Helicobacter pylori–negative volunteers, consisting of 5 homozygous extensive metabolizers (EMs), 6 heterozygous EMs, and 4 poor metabolizers (PMs) of CYP2C19, took 20 mg Rabeprazole, 40 mg Rabeprazole, and 20 mg Rabeprazole plus 20 mg famotidine at bedtime (at 10 PM) for 8 days. The subjects then underwent 24-hour intragastric pH monitoring on day 8. Results For the 20-mg Rabeprazole, 40-mg Rabeprazole, and concomitant dosage regimens, the median percent times and ranges when nocturnal intragastric pH values were lower than 4.0 were 78.8% (47.5%-98.0%), 45.3% (29.0%-52.2%), and 15.5% (0.0%-40.8%), respectively, for homozygous EMs; 51.0% (7.0%-91.6%), 41.3% (33.0%-59.0%), and 18.5% (8.4%-31.9%), respectively, for heterozygous EMs; and 4.5% (2.0%-31.2%), 9.5% (0.0%-31.1%), and 9.3% (0.0%-14.7%), respectively, for PMs. Although significant differences in acid inhibition between the different CYP2C19 genotypes were observed when Rabeprazole alone was given (P = .016 for 20 mg Rabeprazole and P = .023 for 40 mg Rabeprazole), such differences were not observed when famotidine was concomitantly given (P = .206). Conclusions The combination regimen of famotidine plus Rabeprazole is more effective for nocturnal acid inhibition in homozygous and heterozygous EMs than the increased dosage regimen of Rabeprazole. This concomitant therapy could be a rescue regimen for patients with nocturnal acid breakthrough refractory to a standard PPI therapy who are likely to be CYP2C19 EMs. Clinical Pharmacology & Therapeutics (2005) 77, 302–311; doi: 10.1016/j.clpt.2004.10.010
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different dosage regimens of Rabeprazole for nocturnal gastric acid inhibition in relation to cytochrome p450 2c19 genotype status
Clinical Pharmacology & Therapeutics, 2004Co-Authors: Takahisa Furuta, Naohito Shirai, Masayoshi Kajimura, Mitsushige Sugimoto, Akira HishidaAbstract:Objective For the treatment of gastroesophageal reflux disease, intragastric pH should be lower than 4.0 for no more than 4 hours a day (<16.7%). We aimed to develop optimal dosage regimens for Rabeprazole to control nocturnal acidity in relation to cytochrome P450 (CYP) 2C19 genotypes. Methods Fifteen Helicobacter pylori–negative volunteers, comprising 5 homozygous extensive metabolizers (EMs), 6 heterozygous EMs, and 4 poor metabolizers (PMs) of CYP2C19, took placebo and Rabeprazole, at a dose of 20 or 40 mg once daily (at 10 PM) for 8 days. Plasma Rabeprazole concentrations and 24-hour intragastric pH were determined on days 7 and 8, respectively. Because the nocturnal intragastric pH was lower than 4.0 for more than 16.7% of the time with once-daily regimens in homozygous EMs and heterozygous EMs, they were administered 20 mg Rabeprazole twice daily (8 AM and 10 PM) or 10 mg Rabeprazole 4 times daily (8 AM, 12:30 PM, 6 PM, and 10 PM). Results With 40 mg Rabeprazole once daily, the median percent time with nocturnal pH lower than 4.0 was less than 16.7% in PMs (9.5% [range, 3.0%-31.1%]) but not in homozygous EMs (45.3% [range, 29.0%-52.2%]) (P = .043) and heterozygous EMs (41.3% [range, 33.0%-59.0%]) (P = .043). The mean plasma Rabeprazole concentrations differed among the different CYP2C19 genotype groups. With 20 mg Rabeprazole twice daily and 10 mg Rabeprazole 4 times daily, the median percent times with nocturnal pH lower than 4.0 were 5.0% (range, 0.0%-42.0%) and 1.0% (range, 5.0%-7.1%) in heterozygous EMs and 62.0% (range, 10.8%-68.3%) and 14.7% (range, 0.0%-41.7%) in homozygous EMs, respectively, and plasma concentrations were sustained longer than with the once-daily regimens. Conclusions We propose that Rabeprazole dosage regimens for sufficient acid inhibition are 20 mg once daily for PMs, 20 mg twice daily for heterozygous EMs, and 10 mg 4 times daily for homozygous EMs or heterozygous EMs. Clinical Pharmacology & Therapeutics (2004) 76, 290–301; doi: 10.1016/j.clpt.2004.06.008
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comparison of Rabeprazole 20 mg versus omeprazole 20 mg in the treatment of active duodenal ulcer a european multicentre study
Alimentary Pharmacology & Therapeutics, 1999Co-Authors: C P M Dekkers, J A Beker, B Thjodleifsson, A Gabryelewicz, N E Bell, T. J. HumphriesAbstract:Background: Rabeprazole sodium is the newest member of a class of substituted benzimidazole molecules known as proton pump inhibitors. Other proton pump inhibitors have been shown to be effective in healing active duodenal ulcer. Method: This randomized, double-blind, multicentre study, conducted at 25 European sites, compared the efficacy and tolerability of Rabeprazole and omeprazole in patients with active duodenal ulcers. One hundred and two patients with active duodenal ulcer received Rabeprazole 20 mg and 103 patients omeprazole 20 mg once daily for 2 or 4 weeks, with ulcer healing monitored by endoscopy. Results: After 2 weeks, complete ulcer healing was documented in 69% of patients given Rabeprazole 20 mg and in 62% of patients given omeprazole 20 mg (N.S.). After 4 weeks, healing rates were 98% in the Rabeprazole group and 93% in the omeprazole group (P = 0.083). Rabeprazole-treated patients had significantly greater improvement in daytime pain symptom relief than those treated with omeprazole at the conclusion of the study (P = 0.038). Both drugs were well tolerated over the 4-week treatment period. Mean changes from baseline to end-point in fasting serum gastrin were significantly greater in the Rabeprazole group, but at end-point mean values were well within normal limits for both groups. No clinically meaningful changes or other between-group differences were observed in laboratory parameters. Conclusion: In this study, Rabeprazole produced healing rates equivalent to omeprazole at weeks 2 and 4, and provided significantly greater improvement in daytime pain. Both treatments were well tolerated.
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double blind placebo controlled comparison of Rabeprazole 20 mg vs omeprazole 20 mg in the treatment of erosive or ulcerative gastro oesophageal reflux disease
Alimentary Pharmacology & Therapeutics, 1999Co-Authors: C P M Dekkers, J A Beker, B Thjodleifsson, A Gabryelewicz, N E Bell, T. J. HumphriesAbstract:Background: Rabeprazole sodium is the most recent member of a class of substituted benzimidazole molecules known as proton pump inhibitors. Other proton pump inhibitors have been shown to be effective in healing oesophagitis. Methods: In this randomised, double-blind, multicentre study, conducted at 27 European sites, the efficacy and safety of Rabeprazole and omeprazole were compared in patients with erosive or ulcerative gastro-oesophageal reflux disease (GERD).100 patients received Rabeprazole 20 mg, and 102 patients omeprazole 20 mg once daily for 4 or 8 weeks, with healing monitored by endoscopy. Results: Overall GERD healing rates observed and evaluated at weeks 4 and 8 were equivalent. Four-week healing rates for Rabeprazole and omeprazole were 81%–81% and 92%–94% for 8-week healing. Rabeprazole-treated patients had similar relief of the frequency and intensity of heartburn to those treated with omeprazole. Both drugs were well tolerated over the 8-week treatment period. Mean changes in fasting serum gastrin were comparable. No significant differences in laboratory parameters were seen. Biopsies for argyrophil ECL cell histology at the end-point revealed a similar distributions of hyperplasia grades to those at baseline in both groups. Biopsies of body and antral mucosa for other parameters were similar between treatments for Helicobacter pylori colonization, presence or degree of inflammation, atrophy or intestinal metaplasia at the end-point. Conclusion: In this study, GERD healing rates following Rabeprazole 20 mg once daily were equivalent to those obtained with omeprazole 20 mg once daily. Both treatments resulted in a comparable relief of the frequency and intensity of heartburn associated with this disease, and both were well tolerated.
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Rabeprazole in Treatment of Acid Peptic Diseases (Results of Three Placebo-Controlled Dose-Response Clinical Trials in Duodenal Ulcer, Gastric Ulcer, and Gastroesophageal Reflux Disease (GERD))
Digestive Diseases and Sciences, 1998Co-Authors: M. L. Cloud, N. Enas, T. J. Humphries, S. Bassion, The Rabeprazole Study GroupAbstract:Rabeprazole, a new proton pump inhibitor, wasstudied in patients with acid-pepticrelated diseases(duodenal ulcer, gastric ulcer, GERD) in threeplacebo-controlled, double-blind, randomized clinicaltrials. Men and women over the age of 18 were enrolledif the presence of an active duodenal or gastric ulceror erosive or ulcerative esophagitis was confirmed onupper gastrointestinal endoscopy. Patients were randomly allocated to either placebo orRabeprazole 20 mg or 40 mg in the duodenal and gastriculcer protocols or to placebo or Rabeprazole 10 mg, 20mg, or 40 mg in the GERD protocol. All doses ofRabeprazole in all three studies were statisticallysignificantly superior to placebo in healingacid-related lesions. There were no treatmentdifferences between the Rabeprazole doses in healingactive peptic lesions. The incidence of positive [^13C]ureabreath test for H. pylori was 53% in patients withduodenal or gastric ulcers. H. pylori status was noteffected by treatment with Rabeprazole.
