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H Intragastric pH (h + intragastric_ph)
Selected AbstractsClinical trial: Inhibitory effect of revaprazan on gastric acid secretion in healthy male subjectsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2010Hyung-Keun Kim Abstract Background and Aim:, Revaprazan is a novel acid pump antagonist. The aim of this study was to investigate the inhibitory effect of revaprazan on gastric acid secretion in healthy male subjects. Methods:, In a double-blind, three-way cross-over study, 30 healthy male volunteers were randomized to 100, 150 or 200 mg of oral revaprazan daily for 7 days. Serum gastrin concentration was measured, and 24-h intragastric pH was recorded at baseline and on days 1 and 7 of each administration period. Serial blood samples were processed for pharmacokinetics. Results:, Median intragastric pH over 24 h and mean percentage time that pH was > 4 increased in a dose-dependent manner and were significantly higher on days 1 and 7 compared with baseline in all groups (P < 0.05). The antisecretory effect of revaprazan was rapid and nearly maximal on day 1 in all groups. Serum gastrin levels were rapidly normalized by 100 and 150 mg/day of revaprazan on days 1 and 7, but were significantly higher in the 200 mg/day revaprazan group. The pharmacokinetic effect was rapidly absorbed and eliminated on days 1 and 7 in all groups. Conclusions:, Revaprazan rapidly and effectively inhibits gastric acid secretion in healthy male subjects. Therefore, revaprazan can be used as an effective drug for acid-related disease. [source] The effect of time-of-day dosing on the pharmacokinetics and pharmacodynamics of dexlansoprazole MR: evidence for dosing flexibility with a Dual Delayed Release proton pump inhibitorALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2010R. D. LEE Aliment Pharmacol Ther,31, 1001,1011 Summary Background, Dexlansoprazole MR is a Dual Delayed Release proton pump inhibitor formulated to extend the duration of acid suppression. Aim, To evaluate the pharmacokinetics and pharmacodynamics of dexlansoprazole MR dosed before 4 different meal times. Methods, In this randomized, open-label, four-way crossover study, 48 healthy subjects received dexlansoprazole MR 60 mg once daily 30 min before breakfast, lunch, dinner or an evening snack. Pharmacokinetics of dexlansoprazole MR and intragastric pH were assessed over a 24-h postdose interval on day 5 for each regimen. Results, Absorption was delayed when dexlansoprazole MR was administered before each regimen relative to breakfast; however, systemic exposures of dexlansoprazole at all regimens were bioequivalent. There were no statistically significant differences in mean 24-h intragastric pH between dosing before dinner or an evening snack vs. breakfast; however, there was a small (0.2), but statistically significant difference between lunch and breakfast. There was a statistically significant difference of 7 percentage points in the percentage of time intragastric pH was >4 for the snack regimen relative to the breakfast regimen, but there were no statistically significant differences between lunch or dinner compared with breakfast. Conclusion, Dexlansoprazole MR provides comparable acid control when administered at different times of the day. [source] The pharmacodynamics and pharmacokinetics of S-tenatoprazole-Na 30 mg, 60 mg and 90 mg vs. esomeprazole 40 mg in healthy male subjectsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2010R. H. HUNT Aliment Pharmacol Ther,31, 648,657 Summary Background, Racemic tenatoprazole 40 mg/day provides more prolonged acid suppression than esomeprazole 40 mg/day. Aim, To compare pharmacodynamic and pharmacokinetic profiles of tenatoprazole and esomeprazole. Methods, A single-centre, double-blind, double-dummy, randomized, 4-way, cross-over study was conducted in 32 healthy male subjects. S-tenatoprazole-Na 30, 60 or 90 mg, or esomeprazole 40 mg was administered once daily for 5 days with 10-day washout intervals. The 24-h intragastric pH was recorded at baseline and on day 5 of each period. Results, On day 5, median pH (5.34 ± 0.45 and 5.19 ± 0.52 vs. 4.76 ± 0.82, respectively, P < 0.002) and percentage time with pH > 4 (80 ± 11 and 77 ± 12, vs. 63 ± 11 respectively, P < 0.0001) for 24-h were higher with S-tenatoprazole-Na 90 mg and 60 mg than esomeprazole. In nocturnal periods, S-tenatoprazole-Na 90 mg, 60 mg and 30 mg were superior to esomeprazole with regard to median pH (5.14 ± 0.64, 4.94 ± 0.65, 4.65 ± 0.86 and 3.69 ± 1.18 respectively, P < 0.0001) and percentage time with pH > 4 (77 ± 12, 73 ± 17, 64 ± 17 and 46 ± 17 respectively, P < 0.0001). Proportion of subjects with nocturnal acid breakthrough with S-tenatoprazole-Na 90 mg, 60 mg and 30 mg was significantly less than with esomeprazole (54.8, 43.3, 56.7 and 90.3 respectively, P < 0.04). The proportion of subjects with >16 hrs with pH >4 was significantly higher with S-tenatoprazole-Na 90 mg and 60 mg than with esomeprazole (87.1%, 83.3% and 41.9% respectively, P < 0.02). Conclusions, S-tenatoprazole-Na produced significantly greater and more prolonged dose-dependent 24-h and nocturnal acid suppression than esomeprazole. S-tenatoprazole-Na may provide greater clinical efficacy compared with current PPIs for patients with ineffective once-daily therapy. [source] Combined analysis of three crossover clinical pharmacology studies of effects of rabeprazole and esomeprazole on 24-h intragastric pH in healthy volunteersALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2007V. NORRIS Summary Aim To compare antisecretory effects of rabeprazole and esomeprazole after single and repeat dosing in Helicobacter pylori -negative healthy volunteers. Methods Results were pooled from three smaller, open, crossover, randomized studies to obtain data from 80 subjects. The studies compared: (a) 5 days' dosing of 20 mg rabeprazole and esomeprazole (n = 24); (b) single doses of rabeprazole 20 mg and esomeprazole 40 mg (n = 27) and (c) 5 days' dosing of rabeprazole 10 mg and esomeprazole 20 mg (n = 29). Washout periods were ,14 days. Intragastric pH was recorded continuously for 24 h on days 0, 1 and 5. Results Single doses of rabeprazole 20 mg maintained 24-h intragastric pH >4 for longer than esomeprazole 20 mg (45% vs. 32%; P < 0.001); rabeprazole 20 mg and esomeprazole 40 mg were equivalent in their effects. After 5 days' dosing, rabeprazole 20 mg maintained pH >4 for longer than esomeprazole 20 mg (62% vs. 56%; P = 0.046); the reverse was true for esomeprazole 20 mg vs. rabeprazole 10 mg (56% vs. 48%; P = 0.035). In general, intragastric pH AUC during 0,5 h after dosing was higher after esomeprazole than rabeprazole, whereas the reverse was true during the night. Conclusions The order of effects on 24-h pH was: rabeprazole 10 mg , esomeprazole 20 mg < rabeprazole 20 mg = esomeprazole 40 mg. Esomeprazole acts faster, whereas rabeprazole's effect lasts longer. [source] Oral rabeprazole vs. intravenous pantoprazole: a comparison of the effect on intragastric pH in healthy subjectsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2007D. ARMSTRONG Summary Background Intravenous pantoprazole is often administered inappropriately to hospitalized patients who can take oral medications. Aim To compare the antisecretory effects of oral rabeprazole and intravenous pantoprazole in healthy subjects. Methods In a double-blind, double-dummy, two-way crossover study, 38 Helicobacter pylori -negative volunteers were randomized to oral rabeprazole 20 mg or intravenous pantoprazole 40 mg daily for 3 days followed, after a 14-day washout period by the comparator treatment. Intragastric pH was recorded continuously for 24 h at baseline and on days 1 and 3 of each treatment period. Results The mean (95% CI) percentage of the 24-h recording with gastric pH >4 was higher with rabeprazole than with pantoprazole on day 1: 37.7% (30.6,44.8%) vs. 23.9% (20.0,27.8). The mean percentage times with pH >3 and >4 for all intervals assessed were greater and the median 24-h intragastric pH values were higher with rabeprazole than with pantoprazole on days 1 and 3. The mean acidity index was lower with rabeprazole on days 1 and 3. Conclusions Oral rabeprazole 20 mg produced greater acid suppression than intravenous pantoprazole 40 mg. Therefore, it may be an appropriate and effective alternative in patients who can take oral medication. [source] Effect of concomitant dosing of famotidine with lansoprazole on gastric acid secretion in relation to CYP2C19 genotype statusALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2005T. FURUTA Background :,Famotidine increases Helicobacter pylori -eradication rates by a triple lansoprazole/amoxicillin/clarithromycin therapy in patients with the rapid extensive metabolizer genotype of CYP2C19. Aim :,To determine the effect of famotidine on the gastric acid inhibition by lansoprazole in relation to CYP2C19 genotypes. Methods :,Twenty healthy volunteers with different CYP2C19 genotypes , consisting of six rapid extensive metabolizers, nine intermediate metabolizers and five poor metabolizers , underwent three 7-day courses with placebo, lansoprazole 30 mg twice daily, and lansoprazole 30 mg twice plus famotidine 20 mg twice daily. Lansoprazole was dosed after breakfast and dinner. Famotidine was dosed after lunch and at bedtime. Intragastric pH monitoring was performed for 24 h on day 7 of each course. Results :,With placebo, no difference was observed in intragastric pH profiles among the three CYP2C19 genotype groups. With lansoprazole 30 mg twice daily, the median of 24-h intragastric pH in poor metabolizers (6.1) was significantly higher than those of rapid extensive metabolizers (4.5) and intermediate metabolizers (5.0), respectively (P = 0.0176 and 0.0388), whereas with lansoprazole 30 mg twice and famotidine 20 mg twice daily, the medians were 5.4, 5.7, and 6.1, respectively (not significant). Conclusion :,Acid inhibition by lansoprazole was influenced by CYP2C19 genotype status. This influence was offset by the concomitant use of famotidine. [source] Control of intragastric pH with omeprazole 20 mg, omeprazole 40 mg and lansoprazole 30 mgALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2001P. O. Katz Background: Single daily doses of proton pump inhibitors, omeprazole and lansoprazole provide effective acid suppression and equal healing and symptom relief in patients with GERD. Despite this, controversy exists as to the efficacy of available proton pump inhibitors in the control of gastric acidity. Aim: To assess the efficacy of omeprazole 20 mg vs. lansoprazole 30 mg and omeprazole 40 mg vs. lansoprazole 30 mg in intragastric pH control. Methods: Study I: 12 Helicobacter pylori -negative volunteers (mean age 33 years) were treated with omeprazole 20 mg and lansoprazole 30 mg in random order before breakfast for 7 days. Study II: 24 subjects (mean age 36 years) were similarly treated with omeprazole 40 mg and lansoprazole 30 mg for 7 days after a baseline pH study. One week washout was allowed between studies. Subjects had the same meal on each study day. On day seven, a 24-h intragastric pH study was performed. The percentage time for which gastric pH > 4 was analysed (Gastrosoft, Synectics Medical Inc.) and expressed as mean ± s.d. Results: (1) Omeprazole 20 mg and lansoprazole 30 mg showed no significant difference in the percentage time for which gastric pH > 4 in the daytime and night-time periods. (2) The percentage time for which pH > 4 with omeprazole 40 mg was significantly greater than lansoprazole 30 mg in both daytime (61 ± 19% vs. 48 ± 14%, P < 0.001), and night-time periods (34 ± 21% vs. 26 ± 14%, P < 0.05). (3) A large inter-subject variation existed in both studies. (4) In 10 subjects who participated in both studies, omeprazole 40 mg showed a significantly higher percentage time for which pH > 4 in the daytime (69 ± 18% vs. 51 ± 15%, P=0.015) than omeprazole 20 mg. Conclusion: These pH data support the therapeutic equivalency of FDA approved doses of omeprazole and lansoprazole. [source] [13C]-pantoprazole breath test to predict CYP2C19 phenotype and efficacy of a proton pump inhibitor, lansoprazoleALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009T. FURUTA Summary Background,13CO2 is produced on metabolism of 13C-labelled-pantoprazole ([13C]-pantoprazole) by CYP2C19. Aim, To investigate whether the [13C]-pantoprazole breath test can predict CYP2C19 status and efficacy of proton pump inhibitors (PPIs) in Japanese. Methods, We classified 110 healthy volunteers as rapid metabolizers (RM), intermediate metabolizers (IM) or poor metabolizers (PM) of CYP2C19 by genotyping. Breath samples were collected at 10-min intervals for 60 min after dosing with 100 mg [13C]-pantoprazole. Changes in the carbon isotope ratios (13CO2/12CO2) in carbon dioxide in breath samples were measured and expressed as a delta-over-baseline (DOB) ratio (,). Of the 110 subjects, twenty-two randomly selected subjects underwent intragastric pH monitoring on day 7 of dosing with 30 mg of lansoprazole. Results, The DOB values of RMs were the highest and those of PMs the lowest of the three groups. Statistically significant differences were observed in the area-under-the-curve (AUC)20,60 min of DOB among the three groups. The mean 24-h intragastric pHs attained by lansoprazole 30 mg for 7 days were inversely correlated with the AUC20,60 min of DOB. Conclusions, [13C]-pantoprazole breath test can easily estimate the individual activity of CYP2C19 and predict the efficacy of a PPI (i.e. lansoprazole). This test would be useful for individualized medicine with a PPI. [source] | ||||||||||