Differences In Intragastric pH Research Articles

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

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 pylori-negative 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.

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

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. To evaluate the effect of food on the pharmacokinetics (PK) and pharmacodynamics (PD) of dexlansoprazole following oral administration of dexlansoprazole MR. 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. 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. Dexlansoprazole MR can be administered without regard to food or the timing of food in most patients.

Differences in intragastric pH in diabetic vs. idiopathic gastroparesis: relation to degree of gastric retention

Evidence suggests that distinct mechanisms underlie diabetic and idiopathic gastroparesis. Differences in gastric acid in gastroparesis of different etiologies and varying degrees of gastric stasis are uninvestigated. We tested the hypotheses that 1) gastric pH profiles show differential alteration in diabetic vs. idiopathic gastroparesis and 2) abnormal pH profiles relate to the severity of gastric stasis. Sixty-four healthy control subjects and 44 gastroparesis patients (20 diabetic, 24 idiopathic) swallowed wireless transmitting capsules and then consumed (99m)Tc-sulfur colloid-labeled meals for gastric scintigraphy. Gastric pH from the capsule was recorded every 5 s. Basal pH was higher in diabetic (3.64 +/- 0.41) vs. control subjects (1.90 +/- 0.18) and idiopathic subjects (2.41 +/- 0.42; P < 0.05). Meals evoked initial pH increases that were greater in diabetic (4.98 +/- 0.32) than idiopathic patients (3.89 +/- 0.39; P = 0.03) but not control subjects (4.48 +/- 0.14). pH nadirs prior to gastric capsule evacuation were higher in diabetic patients (1.50 +/- 0.23) than control subjects (0.58 +/- 0.11; P = 0.003). Four-hour gastric retention was similar in diabetic (18.3 +/- 0.5%) and idiopathic (19.4 +/- 0.5%) patients but higher than control subjects (2.2 +/- 0.5%; P < 0.001). Compared with control subjects, those with moderate-severe stasis (>20% retention at 4 h) had higher basal (3.91 +/- 0.55) and nadir pH (2.23 +/- 0.42) values (P < 0.05). In subgroup analyses, both diabetic and idiopathic patients with moderate-severe gastroparesis exhibited increased pH parameters vs. those with mild gastroparesis. In conclusion, diabetic patients with gastroparesis exhibit reduced gastric acid, an effect more pronounced in those with severely delayed gastric emptying. Idiopathic gastroparetic subjects exhibit nearly normal acid profiles, although those with severely delayed emptying show reduced acid vs. those with mild delays. Thus both etiology and degree of gastric stasis determine gastric acidity in gastroparesis.

Pharmacokinetic and Pharmacodynamic Properties of Lafutidine after Postprandial Oral Administration in Healthy Subjects: Comparison with Famotidine

Lafutidine, a histamine H(2)-receptor antagonist, inhibits gastric acid secretion during the daytime, however, the relationship between the plasma concentration and the drug response remains unclear. The aim of this study was to compare the pharmacokinetic and pharmacodynamic properties of lafutidine and famotidine following postprandial oral administration. After a lafutidine tablet (10 mg), famotidine tablet (20 mg), or water only (control) was administered, blood samples were taken and intragastric pH was measured. The plasma concentrations of lafutidine and famotidine were determined by HPLC, and the median intragastric pH values per 30 min were used as the degrees of gastric acid suppression. Data were analyzed based on a one-compartment pharmacokinetic model and a sigmoid E(max) pharmacodynamic model. Lafutidine plasma concentrations rapidly increased after administration; famotidine required some time to increase the plasma concentrations, requiring an absorption lag time in the pharmacokinetic model. Between the plasma concentration and DeltapH (the difference in intragastric pH by the drug vs. control), lafutidine showed an anticlockwise hysteresis loop which indicated equilibration delay between the plasma concentration and effect site, requiring an effect site compartment in the pharmacodynamic model; famotidine showed more parallel relationship. These results indicated that the pharmacokinetic and pharmacodynamic properties of lafutidine after postprandial oral administration were different from those of famotidine at least 4.5 h after dosing.

Regional Postprandial Differences in pH Within the Stomach and Gastroesophageal Junction

Our objective was to determine regional differences in intragastric pH after different types of meals. Ten normal subjects underwent 27-hr esophagogastric pH monitoring using a four-probe pH catheter. Meals were a spicy lunch, a high-fat dinner, and a typical bland breakfast. The fatty dinner had the highest postprandial buffering effect, elevating proximal and mid/distal gastric pH to 4.9 +/- 0.4 and 4.0 +/- 0.4, respectively, significantly (P < 0.05) higher compared to 4.2 +/- 0.3 and 3.0 +/- 0.4 for the spicy lunch and 3.0 +/- 0.3 and 2.5 +/- 0.8 for the breakfast. The buffering effect of the high-volume fatty meal to pH > 4 was also longer (150 min) compared to that of the spicy lunch (45 min) and the bland breakfast, which did not increase gastric pH to > 4 at any time. Proximal gastric acid pockets were seen between 15 and 90 min postprandially. These were located 3.4 +/- 0.8 cm below the proximal LES border, extending for a length of 2.3 +/- 0.8 cm, with a drop in mean pH from 4.7 +/- 0.4 to 1.5 +/- 0.9. Acid pockets were seen equally after the spicy lunch and fatty dinner but less frequently after the bland breakfast. We conclude that a high-volume fatty meal has the highest buffering effect on gastric pH compared to a spicy lunch or a bland breakfast. Buffering effects of meals are significantly higher in the proximal than in the mid/distal stomach. Despite the intragastric buffering effect of meals, focal areas of acidity were observed in the region of the cardia-gastroesophageal junction during the postprandial period.

Therapeutic choices in reflux disease: Defining the criteria for selecting a proton pump inhibitor

Gastroesophageal reflux disease (GERD) is among the most common disorders of the gastrointestinal tract, with symptoms affecting a substantial proportion of the US population on a daily basis. Heartburn and related symptoms arise from a number of pathophysiologic mechanisms, including dilated intercellular spaces, increased duration of acid reflux, greater proximal extent of reflux, and esophageal sensitivity. Chronic reflux may result in serious complications, such as esophageal erosions or ulceration, stricture, and Barrett esophagus. The goals of GERD therapy are to relieve patients' symptoms and prevent complications. Proton pump inhibitors (PPIs) represent the most effective treatment option for GERD, relieving symptoms, healing erosions, and maintaining a healed mucosa. Differences in the pharmacokinetics and pharmacodynamics among the PPIs may result in differences in intragastric pH holding time as well as the onset of symptom relief. Lansoprazole and esomeprazole produce similar degrees and onset of symptom relief, with both providing greater symptom relief as compared with omeprazole. Although manufactured as capsules containing enteric-coated granules, lansoprazole, omeprazole, and esomeprazole maintain their high level of pharmacologic efficacy when the capsule contents are emptied into soft foods or various liquids. Lansoprazole and pantoprazole also are manufactured as intravenous formulations, and lansoprazole is available as strawberry-flavored granules for oral suspension and as an orally disintegrating tablet. These alternative routes of administration are particularly beneficial in the management of acid-related disorders in infants, children, the elderly, and patients of all ages who have difficulty swallowing or are unable to swallow intact capsules or tablets and those in the critical care setting.

Gastric pH and volume after oral fluids in the postpartum patient

The aim of this study was to investigate the relationship between preoperative oral fluids and gastric pH and volume in women undergoing sterilization between one and five days postpartum. Fifty postpartum patients received 150 ml water approximately two to three hours before surgery while 50 postpartum and 50 non-pregnant women were fasted from midnight. After induction of anaesthesia, gastric contents were aspirated using a Salem sump tube and the gastric pH and volume were measured. There were no differences in intragastric pH and volume, median (range), among the postpartum fasted group, 1.19 (0.74-4.57), 22 (1-78) ml, postpartum water group 1.18 (0.70-6.4), 25.5 (3-66) ml and the non-pregnant group 1.27 (0.51-6.63), 25 (3-69) ml. There was no correlation between postpartum interval, 60 (12-120) hr, and intragastric pH or volume. It is concluded that oral water may be given safely two to three hours preoperatively to patients more than one day postpartum. Intragastric volume and acidity were not increased and the findings in postpartum patients were similar to those found in non-pregnant patients.