Inhibitory potency of twice-a-day omeprazole on gastric acidity is enhanced by eradication of H. pylori in duodenal ulcer patients.

The gastric pH-elevating effect of proton pump inhibitors such as omeprazole has been reported to be greater in the presence than in the absence of an H. pylori infection. It is unknown if this effect persists when a higher dose of omeprazole is taken. We undertook both 24-hr pH-metry and 24-hr aspiration studies in 12 H. pylori-positive patients with a history of duodenal ulcer (DU); (1) when not on omeprazole; (2) when on omeprazole 20 mg twice a day for 8 days; (3) two months after eradication of H. pylori and when not on omeprazole; and (4) after eradication of H. pylori and when on omeprazole twice a day. Eradication of H. pylori in DU results in lower mean and median pH; decreased percent pH > or = 3/ > or = 4, and greater median H+ after breakfast, after lunch, and overnight; and omeprazole appears to have less of a pH-elevating effect in the absence than in the presence of an H. pylori infection. The fall in gastric juice NH3 concentration as a result of eradicating H. pylori partially explained the lower pH-elevating effect of omeprazole. The variation in acid inhibitory effect of omeprazole after as compared with before eradication of H. pylori could not be explained by differences; (1) in gastric juice concentrations of IL-1alpha, IL-8, IL-13, or epidermal growth factor; (2) in the fasting or fed total concentration of gastric juice bile acids; (3) in the fasting concentrations or area under-the-curve (AUC) of the gastric H+ concentrations in response to food; or (4) in the pharmacokinetics of omeprazole. The difference in H+ AUC without omeprazole minus with omeprazole was actually greater when compared after versus before eradication of H. pylori. Thus, in DU the pH-elevating potency of omeprazole taken twice a day is greater in the presence than in the absence of an H. pylori infection.

Food but not a chemically defined diet interferes with maintenance of intragastric pH at a predefined level using continuous pH-stat-adjusted intravenous infusion of ranitidine in healthy volunteers.

Eight healthy volunteers were used to determine the influence of a normal diet (food) versus an isocaloric chemically defined diet (CDD) on the dose of ranitidine infused continuously over 12 hr, required to maintain the intragastric pH > or = 5 or above. The dose of ranitidine used was adjusted by the pH-stat instrument, Gastrojet, and a target pH of 5.0 was selected. The average ranitidine dose was 43.5 mg for food, 28.3 mg for CDD, and 25.7 mg for fasting. Despite the higher dose of ranitidine used with food, the control of pH was lower than the desired and preset value of pH > or = 5: the average mean pH was 3.99 for food, 5.11 for CDD, and 5.75 for fasting. The percentage of time of pH > or = 5 was 32.0% for food, 73.7% for CDD, and 80.1% for fasting. Thus, when persons are fed a normal diet there is a need for higher doses of ranitidine to maintain the gastric pH > or = 5.0. Even with frequent monitoring of intragastric pH with the Gastrojet, there is much greater variability in pH control with food than with CDD or fasting, and the preset and desired pH level was not achieved. This difficulty in achieving desired end points of pH control when switching from a fasting to a fed state needs to be considered when intravenous ranitidine is used to obtain strict control of intragastric pH.

Pharmacokinetics and pharmacodynamics during treatment with the omeprazole 20 mg enteric-coated tablet and 20 mg capsule in asymptomatic duodenal ulcer patients.

This study compared the 24 h intragastric pH profile and bioavailability at repeated dosing conditions of the omeprazole 20 mg enteric-coated tablet versus the 20 mg capsule. Forty duodenal ulcer patients in asymptomatic remission completed this randomized open two-way crossover study. Omeprazole 20 mg tablets or capsules were administered for seven days in each period. A 24 h pH recording was performed before the start of treatment and on day 7 of each treatment period. Plasma concentrations of omeprazole were determined 24 h after the dose. The treatment periods were separated by two to four weeks. The difference in percentage of time with pH of at least 3 was less than 16% in favour of the tablet (not significant). The estimated mean area under the plasma concentration-time curve as well as the maximum plasma concentration (Cmax) for omeprazole were 18% and 41% higher, respectively, for the tablet versus the capsule, with the latter percentage being statistically significant. The time to reach Cmax (tmax) with the tablet was, on average, about 0.5 h longer than to reach the tmax of the capsule. This study indicates that the enteric-coated tablet formulation of omeprazole is biodynamically equivalent to the capsule regarding their effects on intragastric pH during repeated dosing.