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Intragastric pH (intragastric + ph)

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Medical Sciences	100%

Kinds of Intragastric pH

h intragastric ph

Selected Abstracts

Effect of paddock vs. stall housing on 24 hour gastric pH within the proximal and ventral equine stomach

EQUINE VETERINARY JOURNAL, Issue 4 2008
L. HUSTED
Summary Reasons for performing study: Stall housing has been suggested as a risk factor for ulcer development in the equine stomach; however, the exact pathogenesis for this has not been established. Objectives: To investigate the effect of 3 environmental situations (grass paddock, stall alone or stall with adjacent companion) on pH in the proximal and the ventral stomach. Methods: Six horses with permanently implanted gastric cannulae were used in a randomised, cross-over, block design. Each horse rotated through each of three 24 h environmental situations. Horses remained on their normal diet (grass hay ad libitum and grain b.i.d.) throughout the study. Intragastric pH was measured continuously for 72 h just inside the lower oesophageal sphincter (proximal stomach) and via a pH probe in the gastric cannula (ventral stomach). Results: Neither proximal nor ventral 24 h gastric pH changed significantly between the 3 environmental situations. Mean hourly proximal gastric pH decreased significantly in the interval from 01.00,09.00 h compared to the interval from 13.00,20.00 h, regardless of environmental situation. Median hourly proximal pH only differed in the interval from 06.00,07.00 h compared to the interval 14.00,19.00 h. Neither mean nor median hourly ventral gastric pH varied significantly with the time of day. Conclusions: The change in housing status used in the current study did not affect acid exposure within either region of the equine stomach. The pH in the ventral stomach was uniformly stable throughout the study, while the proximal pH demonstrated a 24 h circadian pattern. Potential relevance: Since stall housing was not associated with prolonged acid exposure to the proximal stomach, this aspect alone does not explain the increased risk of squamous ulcer development. The circadian rhythm associated with proximal intragastric pH warrants further investigation. [source]

Clinical trial: gastric acid suppression in Hispanic adults with symptomatic gastro-oesophageal reflux disease , comparator study of esomeprazole, lansoprazole and pantoprazole

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010
D. Morgan
Aliment Pharmacol Ther 2010; 32: 200,208 Summary Background, Hispanic-Americans are a rapidly growing population in the United States, yet gastro-oesophageal reflux disease (GERD) is not well studied in this population. Aim, To compare the efficacy of esomeprazole, lansoprazole and pantoprazole in suppressing gastric acid, including the area of the ,acid pocket,' in Hispanics with GERD. Methods, In this open-label, 3-way crossover study, 83 Hispanics with symptomatic GERD were randomized to 1 of 6 possible treatment sequences of three 5,7-day dosing periods with esomeprazole 40 mg, lansoprazole 30 mg and pantoprazole 40 mg daily separated by 10,17-day washout periods. Intragastric pH was measured for 24 h using dual probes with a distal and proximal (area of the ,acid pocket') electrode. Results, Esomeprazole suppressed intragastric acid (pH >4.0) significantly longer over 24 h (primary end point) compared with lansoprazole and pantoprazole (P < 0.0001), and proximal gastric acid (pH >4.0) significantly longer over 24 h compared with lansoprazole (P < 0.05) and pantoprazole (P < 0.0001). Conclusions, Esomeprazole was more effective than lansoprazole and pantoprazole in suppressing gastric acidity at both intragastric distal and proximal (area of the acid pocket) sites in Hispanics with GERD. Future studies are warranted to understand better the role of the acid pocket in GERD (Clinical trial numbers: D9612L00106; ClinicalTrials.gov: NCT00410592). [source]

Clinical trial: the effect and timing of food on the pharmacokinetics and pharmacodynamics of dexlansoprazole MR, a novel Dual Delayed Release formulation of a proton pump inhibitor , evidence for dosing flexibility

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2009
R. D. LEE
Summary Background Dexlansoprazole MR is a proton pump inhibitor with a Dual Delayed Release (DDR) formulation designed to prolong the dexlansoprazole plasma concentration,time profile. The presence of food or time of dosing relative to food may affect dexlansoprazole absorption. Aims To evaluate the effect of food on the pharmacokinetics (PK) and pharmacodynamics (PD) of dexlansoprazole following oral administration of dexlansoprazole MR. Methods In this open-label, single-dose, randomized, 4-way crossover study, 48 healthy subjects received placebo (day 1) and dexlansoprazole MR 90 mg (day 3) after fasting, 5 or 30 min before a high-fat breakfast, or 30 min after a high-fat breakfast. Intragastric pH (days 1 and 3) and PK (day 3) of dexlansoprazole were assessed over a 24-h interval after each dose. Results Following administration of dexlansoprazole MR under fasted/fed conditions, mean dexlansoprazole plasma concentration,time profiles generally exhibited two distinct peaks, resulting from the DDR formulation. Increases in dexlansoprazole maximum plasma concentration (12,31%) and area under the plasma concentration,time curve (9,21%) were observed with the fed regimens; however, differences in intragastric pH were not considered clinically relevant. Conclusion Dexlansoprazole MR can be administered without regard to food or the timing of food in most patients. [source]

Combined analysis of three crossover clinical pharmacology studies of effects of rabeprazole and esomeprazole on 24-h intragastric pH in healthy volunteers

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2007
V. 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 subjects

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2007
D. 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 low-dose rabeprazole and omeprazole on gastric acidity: results of a double blind, randomized, placebo-controlled, three-way crossover study in healthy subjects

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2004
S. Bruley des Varannes
Summary Background :,The treatment of acid-related symptoms requires rapid and consistent acid suppression, especially with on-demand regimens. Aim :,To compare the antisecretory activity of low-dose rabeprazole and omeprazole in healthy, Helicobacter pylori -negative subjects. Methods :,In this randomized, double-blind, placebo-controlled, three-way crossover study, 27 volunteers were given rabeprazole 10 mg, omeprazole 10 mg, or placebo once daily for 7 days with a 10,14-day washout between treatments. Intragastric pH was monitored for 24-h on days 1 and 7 of each treatment. Results :,Median gastric pH was significantly higher with rabeprazole than with omeprazole or placebo: day 1: 2.3, 1.4 and 1.3, respectively (P = 0.0056, rabeprazole vs. omeprazole; P < 0.0001, rabeprazole vs. placebo); day 7: 3.7, 2.2 and 1.3, respectively (P = 0.0016 rabeprazole vs. omeprazole; P < 0.0001, rabeprazole vs. placebo). Time with gastric pH above 4 was significantly higher with rabeprazole than with omeprazole: day 1, 5.8 h vs. 3.7 h, respectively (P < 0.02); day 7, 10.5 h vs. 4.6 h, respectively (P = 0.0008). Conclusions :,Rabeprazole 10 mg provides more rapid acid inhibition compared with omeprazole 10 mg. After 7 days, the time with pH above 4 is more than doubled with rabeprazole 10 mg vs. omeprazole 10 mg. [source]

Gastric Acidity in Patients with Follicular Gastritis is Significantly Reduced, but Can be Normalized After Eradication for Helicobacter pylori

HELICOBACTER, Issue 3 2005
Tomohiko Shimatani
ABSTRACT Background., Follicular gastritis is thought to be caused by Helicobacter pylori infection. However, the pathophysiology of it remains unclear. Materials and methods., We assessed gastric acidity in 15 patients with follicular gastritis, aged 20,37 years, using a 24-hour intragastric pH-metry, as well as by histologic and serologic evaluations; and compared it with that in other age-matched groups: 18 cases of H. pylori -positive antrum-predominant gastritis, 12 of pangastritis, and 24 H. pylori -negative normals. In eight cases with follicular gastritis, it was re-assessed 6 months after the eradication therapy for H. pylori. Results., During nighttime, the percentage of time with intragastric pH above 3.0 in follicular gastritis was significantly higher than that in normals (p < .0001), and in antrum-predominant gastritis (p < .001), but was comparable with that in pangastritis. In the daytime period, this parameter in follicular gastritis was significantly higher than that in normal (p < .001), in antrum-predominant gastritis (p < .001), and in pangastritis (p < .05). Marked mononuclear cell and neutrophil infiltration but no apparent glandular atrophy were observed in both the antrum and corpus. Serum pepsinogen I/II ratio was significantly lower in follicular gastritis than that in normals (p < .0001) and in antrum-predominant gastritis (p < .001), whereas serum gastrin was significantly higher than that in normals (p < .0001), in antrum-predominant gastritis (p < .01) and in pangastritis (p < .05). After eradication for H. pylori, all of the parameters in follicular gastritis were altered to the same ranges as those in normals. Conclusions., In follicular gastritis, gastric acidity is significantly reduced, but can be normalized by eradication of H. pylori. It can thus be speculated that inflammatory cytokines or H. pylori -infection,induced prostaglandins might strongly inhibit gastric acid secretion in follicular gastritis. [source]

Clinical trial: Inhibitory effect of revaprazan on gastric acid secretion in healthy male subjects

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2010
Hyung-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]

Low-dose intravenous pantoprazole for optimal inhibition of gastric acid in Korean patients

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2007
Jung-Hwan Oh
Abstract Background and Aim:, Proton-pump inhibitor (PPI) therapy for bleeding ulcers is more efficacious in Asian patients than in non-Asian patients. The aim of this study was to evaluate the efficacy of various doses of pantoprazole on intragastric acidity in Korean patients. Methods:, A prospective randomized study was conducted in 52 patients either with bleeding peptic ulcers after successful endotherapy or who received endoscopic mucosal resection for gastric neoplasms. Patients were randomized into two doses of intravenous pantoprazole: 40 mg q.d. and 40 mg b.i.d. We compared these results with our preliminary study utilizing high-dose pantoprazole (80 mg + 8 mg/h). The potential contribution of CYP2C19 genetic polymorphisms and the presence of Helicobacter pylori were also assessed. Results:, Pantoprazole 40 mg b.i.d. and high-dose pantoprazole demonstrated better inhibition of intragastric acid than pantoprazole q.d. (P < 0.05). The pantoprazole 40 mg q.d. group exhibited significant variations in acid inhibition correlating with CYP2C19 genotype. Median 24 h pH values did not differ significantly between the pantoprazole b.i.d. and high-dose pantoprazole groups, regardless of H. pylori infection status. A median intragastric pH < 6.0 was observed in only three of 28 patients in the 40 mg b.i.d. group; these three patients were extensive metabolizers. Conclusion:, A 40 mg b.i.d. dose of pantoprazole is sufficient to maintain pH > 6.0 in Korean patients, except for patients with extensive metabolizing CYP2C19 genotypes. [source]

Effects of a single dose of rabeprazole 20 mg and pantoprazole 40 mg on 24-h intragastric acidity and oesophageal acid exposure: a randomized study in gastro-oesophageal reflux disease patients with a history of nocturnal heartburn

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2010
P. MINER
Aliment Pharmacol Ther,31, 991,1000 Summary Background, Nocturnal heartburn is common in patients with gastro-oesophageal reflux disease (GERD). Aim, To compare the effects of single doses of rabeprazole 20 mg and pantoprazole 40 mg on 24-h intragastric acidity and oesophageal acid exposure (OAE). Methods, A total of 52 subjects with GERD and a ,6-month history of heartburn were randomized into a blinded, 2 × 2 crossover trial. Subjects' intragastric pH was monitored in two 48-h study periods with 6- to 13-day washout between periods. Patients received placebo on day 1, a single dose of rabeprazole 20 mg or pantoprazole 40 mg on day 2, and standardized meals throughout. Results, The mean percentage time with intragastric pH >4 was significantly greater with rabeprazole vs. pantoprazole for the 24-h postdose interval (44.0% vs. 32.8%; P < 0.001). Significant differences were observed in the daytime (51.0% vs. 42.2%; P < 0.001) and nighttime (32.0% vs. 16.9%; P < 0.001). Rabeprazole was also significantly superior in other intragastric pH parameters. There was no statistical difference for OAE between treatments. Conclusions, In GERD patients with nocturnal heartburn, rabeprazole 20 mg was significantly more effective than pantoprazole 40 mg in percentage time with intragastric pH >4 during the nighttime, daytime, and 24-h periods. Differences between treatments in OAE were not demonstrated. This trial is registered with http://clinicaltrials.gov, number NCT00237367. [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 inhibitor

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2010
R. 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]

Omeprazole-Mg 20.6 mg is superior to lansoprazole 15 mg for control of gastric acid: a comparison of over-the-counter doses of proton pump inhibitors

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010
P. B. MINER JR
Aliment Pharmacol Ther,31, 846,851 Summary Background, Over-the-counter (OTC) proton pump inhibitors (PPIs) relieve heartburn by decreasing the production of gastric acid, but may not do so with equal effectiveness. It is important for healthcare professionals to compare the ability of OTC PPIs to control gastric acid when recommending them for patients with frequent heartburn. Aim, To compare the effects of omeprazole-Mg 20.6 mg and lansoprazole 15 mg (OTC doses in the US) on 24-h steady state gastric acid suppression. Methods, This single-centre, randomized, double-blind clinical study compared the steady-state gastric acid control of omeprazole-Mg 20.6 mg vs. lansoprazole 15 mg, dosed before breakfast. Volunteers were enrolled in a 3-period, cross-over design (ABB, BAA) with 24-h gastric pH monitoring on dosing day 5. The primary efficacy variable was the percentage time intragastric pH was >4.0 over 24 h on day 5 of dosing. Results, Forty subjects were enrolled; all completed the study. The mean (SE) percentage time pH was >4.0 was 45.7% (3.45%) for omeprazole-Mg 20.6 mg and 36.8% (3.45%) for lansoprazole 15 mg, an absolute difference of 8.9% (P < 0.0001), and a relative difference of 24.2%. Both drugs were well tolerated. Conclusion, Omeprazole-Mg 20.6 mg provided a statistically significantly (P < 0.0001) greater acid control than lansoprazole 15 mg. [source]

The pharmacodynamics and pharmacokinetics of S-tenatoprazole-Na 30 mg, 60 mg and 90 mg vs. esomeprazole 40 mg in healthy male subjects

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2010
R. 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]

Clinical trial: intragastric acid control in patients who have Barrett's oesophagus,comparison of once- and twice-daily regimens of esomeprazole and lansoprazole

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2009
S. J. SPECHLER
Summary Background, Gastric acid control is important for treatment of gastro-oesophageal reflux disease associated with Barrett's oesophagus. Substantial indirect evidence suggests that gastric acid control may have a chemopreventive role in Barrett's oesophagus. Aim, To compare the pharmacodynamic efficacy of esomeprazole and lansoprazole at two dosages for intragastric pH control with Barrett's oesophagus. Methods, Patients with Barrett's oesophagus received open-label consecutive treatment (a 15-day period of once-daily dosing followed by a 10-day period of twice-daily dosing) with esomeprazole (40-mg capsules) and lansoprazole (30-mg capsules) in random order with no washouts. Twenty-four-hour intragastric pH was recorded on the last day of each dosing period. The primary end point was the percentage of time with intragastric pH > 4.0. Results, In the per-protocol once- (n = 46) and twice-daily (n = 41) analyses, the percentage of time with intragastric pH > 4.0 was significantly (P < 0.0001) longer after once- (67.1%) or twice-daily (81.2%) esomeprazole than after once- (50.8%) or twice-daily (64.3%) lansoprazole. The proportion of patients with intragastric pH > 4.0 for >12 h was significantly higher for esomeprazole than lansoprazole with once- (P = 0.004) and twice-daily (P = 0.016) dosing. Conclusion, Esomeprazole 40 mg is significantly more effective than lansoprazole 30 mg in controlling intragastric pH with Barrett's oesophagus. [source]

Review article: dual delayed release formulation of dexlansoprazole MR, a novel approach to overcome the limitations of conventional single release proton pump inhibitor therapy

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2009
D. C. METZ
Summary Background, Proton pump inhibitors (PPIs) provide the most effective pharmacotherapy for treating acid-related disorders. However, PPIs do not completely control acid over 24 h with once-daily dosing. Aims, To discuss limitations inherent in the pharmacokinetics (PK) and pharmacodynamics of conventional PPI formulations, which provide a single drug release. Also, to consider approaches to extending the duration of acid suppression focusing on dexlansoprazole MR, a PPI with a novel Dual Delayed Release (DDR) formulation. Method, We reviewed the available literature regarding marketed and investigational PPIs. Results, Non-standard dosing of currently marketed PPIs has produced incremental advances in acid control. Multiple approaches are being evaluated to enhance acid suppression with PPIs. Dexlansoprazole MR is a DDR formulation of dexlansoprazole, an enantiomer of lansoprazole, with two distinct drug release periods to prolong the plasma dexlansoprazole concentration,time profile and extend duration of acid suppression. Clinical studies show that dexlansoprazole MR produces a dual-peak PK profile that maintains therapeutic plasma drug concentrations longer than lansoprazole, with a single-peak PK profile, and increases the percentage of time that intragastric pH >4. Conclusions, Novel drug delivery platforms, including the dexlansoprazole MR DDR formulation, may improve acid suppression and offer benefits over conventional single release PPI formulations. [source]

Clinical trial: the effect and timing of food on the pharmacokinetics and pharmacodynamics of dexlansoprazole MR, a novel Dual Delayed Release formulation of a proton pump inhibitor , evidence for dosing flexibility

Relationship between intragastric acid control and healing status in the treatment of moderate to severe erosive oesophagitis

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2007
P. O. KATZ
Summary Aim, To assess the relationship between the percentage of time intragastric pH >4.0 and healing of erosive oesophagitis. Methods, In this proof-of-concept study, adults with endoscopically verified Los Angeles grade C or grade D erosive oesophagitis were randomly assigned to oral esomeprazole 10 or 40 mg once daily for 4 weeks. On day 5, patients underwent 24-h pH monitoring. At 4 weeks, erosive oesophagitis healing status was endoscopically assessed. Investigators scored gastro-oesophageal reflux disease symptoms on a 4-point scale [none to severe (0,3)] before and 4 weeks after treatment. The percentage of time intragastric pH was >4.0 and healing status were correlated and tested for significance using a Spearman rank correlation (r). Results, 103 patients had evaluable data (mean age, 48.7 years; 65% men). Mean percentages of time with intragastric pH >4.0 on day 5 in patients with healed and unhealed erosive oesophagitis were 61% and 42%, respectively (P = 0.0002), indicating that erosive oesophagitis healing rates were positively related to the percentage of time intragastric pH was >4.0. Greater intragastric acid control correlated with lower final daytime and night-time heartburn and acid regurgitation symptom scores (r = ,0.029, ,0.029 and ,0.021; P = 0.003, 0.003 and 0.032, respectively). Conclusion, A positive relationship between intragastric acid control and erosive oesophagitis healing was demonstrated. [source]

Combined analysis of three crossover clinical pharmacology studies of effects of rabeprazole and esomeprazole on 24-h intragastric pH in healthy volunteers

Oral rabeprazole vs. intravenous pantoprazole: a comparison of the effect on intragastric pH in healthy subjects

Comparison of the effects of fasting morning, fasting evening and fed bedtime administration of tenatoprazole on intragastric pH in healthy volunteers: a randomized three-way crossover study

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2006
A. B. R. THOMSON
Background, The effectiveness of proton pump inhibitors is influenced by meals and administration time. Aim, To compare the effects on intragastric acidity of times of dosing of tenatoprazole, a novel imidazopyridine-based proton pump inhibitor with a prolonged plasma half-life. Methods, This randomized three-period crossover study included 12 Helicobacter pylori -negative healthy subjects, who received tenatoprazole 40 mg either fasting at 7.00 am, fasting at 7.00 pm or fed at 9.30 pm for 7 days, with a 2-week washout between periods. Twenty-four hour intragastric pH was monitored on day 7 of each period. Results, On day 7, median 24-h pH was 4.7, 5.1 and 4.7 after breakfast, dinner and bedtime dosing, respectively (P = 0.11), whereas night-time pH was 4.2, 5.0 and 4.4 (P = 0.13). The mean 24-h percentage of time over pH 4 was 62, 72 and 64 after breakfast, dinner and bedtime dosing, respectively (N.S.), and 54, 68 and 56 during night-time (P = 0.06). Nocturnal acid breakthrough incidence decreased from 100% at baseline to 83%, 55% and 75% after 7.00 am, 7.00 pm and 9.30 pm dosing, respectively (P = 0.18), and its mean duration dropped from 6.2 to 2.8, 1.0 and 2.2 h, respectively (P < 0.05). Conclusion, Seven-day administration of tenatoprazole provides a prolonged duration of acid suppression, especially during the night-time, with little effect of food or time of dosing. [source]

Effect of concomitant dosing of famotidine with lansoprazole on gastric acid secretion in relation to CYP2C19 genotype status

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2005
T. 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]

Evaluation of the pharmacokinetics and pharmacodynamics of intravenous lansoprazole

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2004
J. W. Freston
Summary Aim :,To compare the pharmacokinetics and pharmacodynamics of lansoprazole 30 mg administered intravenously in 0.9% NaCl or in polyethylene glycol, or orally. Methods :,Twenty-nine subjects received lansoprazole orally on days 1,7 and intravenous lansoprazole in NaCl on days 8,14. Blood samples were collected on days 1, 7, 8 and 14. Fasting basal acid output and pentagastrin-stimulated maximal acid output were determined on days ,1, 8, 9 and 15. Thirty-six different subjects received one of four regimen sequences: intravenous lansoprazole in NaCl, intravenous in polyethylene glycol, per orally, or intravenous placebo, each for 5 days. Twenty-four hour intragastric pH was recorded on days 1 and 5. Results :,Intravenous and per oral lansoprazole for 7 days produced equivalent basal acid output and maximal acid output suppression. Pharmacokinetics and mean pH values with intravenous lansoprazole in NaCl or polyethylene glycol were equivalent. Both produced mean pH and percentages of time pH above 3, 4, 5 and 6 that were significantly greater than did per orally. Conclusions :,Intravenous lansoprazole inhibits acid secretion as effectively in NaCl as in polyethylene glycol, and its onset of action is faster than per oral lansoprazole. [source]

Control of intragastric pH with omeprazole 20 mg, omeprazole 40 mg and lansoprazole 30 mg

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2001
P. 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]

CYP2C19 Polymorphism and Proton Pump Inhibitors

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2004
Ulrich Klotz
In different populations three phenotypes have been identified: extensive metabolizers, poor metabolizers and individuals carrying one wild type and one mutant allele (het extensive metabolizers). Systemic exposure to the proton pump inhibitors as expressed by the AUC (area under the plasma level time profiles) is 5,12-times higher in poor metabolizers than in extensive metabolizers. As the pharmacodynamic response (elevation of intragastric pH) to the proton pump inhibitors is related directly to their AUC, a much higher pH can be monitored over 24 hr in poor metabolizers than in extensive metabolizers. Furthermore, clinical efficacy of all proton pump inhibitors depend on maintaining intragastric pH above certain threshold levels and significantly higher eradication rates of Helicobacter pylori have been observed in patients of the poor metabolizers and het extensive metabolizers phenotype if compared to extensive metabolizers. Likewise, limited data suggest that proton pump inhibitors-induced healing rates in gastro-oesophageal reflux disease are apparently higher in poor metabolizers/het extensive metabolizers than in extensive metabolizers of CYP2C19. Therefore initial genotyping for this enzyme and higher dosage in extensive metabolizers is likely to improve the clinical efficacy of proton pump inhibitors. [source]

[13C]-pantoprazole breath test to predict CYP2C19 phenotype and efficacy of a proton pump inhibitor, lansoprazole

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009
T. 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]