Biomedical subjects
Publications and source records attributed to P Sander.
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Explore the source record for details and available documents.
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The effects on intragastric p11 and gastrin secretion of once daily pantoprazole (40 mg) and a new formulation omeprazole (20 mg) in a Multiple Unit Pellet System (MUPS) were investigated during two treatment periods of 7 days each in a randomized crossover study with 16 healthy Helicobacter pylori-negative male volunteers. Intragastric pH was measured using continuous 24 hour pH-metry on days 1 and 7. The results were compared to the baseline curves obtained before each treatment period. On day 1, pantoprazole raised the intragastric pH significantly higher and more quickly than omeprazole MUPS (pH median 1.9 vs. 1.6, baseline pH 1.4). After 7 days, the 24 h gastric pH medians were still in favor of pantoprazole (pH 3.0 vs. 2.8). With respect to the basal gastrin concentration, both treatments resulted in similar increases. For pantoprazole, no differences were observed in AUC and Cmax after single and repeated dosing. However, the new omeprazole MUPS formulation still showed the well-known effect of initial low bioavailability increasing after repeated dosing. Pantoprazole and omeprazole were well tolerated. There seems to be no advantage in the new omeprazole formulation compared with the conventional capsule with regard to bioavailability and increase in intragastric pH. The results of this study confirm former results in which pantoprazole (40 mg) was shown to be significantly superior to omeprazole (20 mg) in elevating intragastric pH.
The aim of this study was to determine the bioavailability of orally administered, crushed pantoprazole tablets after buffering with either 1.4% sodium hydrogencarbonate or 1600 mg magaldrate relative to the intact enteric coated pantoprazole tablet. A single dose, three-period crossover study was performed with 18 healthy male volunteers. The crushed pantoprazole suspension, together with either sodium hydrogencarbonate or magaldrate, was administered via a nasogastral tube. Tmax of crushed pantoprazole was earlier as compared to the intact tablet (0.5 h vs. 3 h) and Cmax was approximately 10% higher due to faster absorption. The bioavailability of the crushed pantoprazole tablet relative to the intact pantoprazole tablet was 93% when using sodium hydrogencarbonate as the buffering agent, and 88% when using magaldrate. Based on the internationally approved confidence intervals for AUC (0.80-1.20) and Cmax (0.70-1.43), the crushed tablet buffered with sodium hydrogencarbonate was shown to be bioequivalent with the intact tablet (point estimates for AUC or Cmax: 0.93 or 1.10). For the crushed tablet buffered with magaldrate (point estimates for AUC or Cmax: 0.88 or 1.12) bioequivalence with the intact tablet could not be formally demonstrated, although the lower confidence limit for AUC of 0.78 was only slightly below the lower limit of the equivalence range of 0.80.
Tachyphylaxis (drug tolerance) is an undesirable condition in drug therapy with histamine-2-receptor antagonists (H2RAs). The concept of overcoming tachyphylaxsis via intravenous (i.v.) administration of proton-pump inhibitors (PPIs) or H2RAs is of significant interest to physicians. In the present study, 32 healthy Helicobacter pylori negative male volunteers were evaluated for the ability of i.v. pantoprazole or i.v. ranitidine to overcome oral ranitidine tachyphylaxis. After 10 days of oral treatment with enteric-coated 300-mg ranitidine tablets once daily in the evening, two groups of 16 volunteers each were randomized to receive either i.v. pantoprazole or i.v. ranitidine for up to 72 h. The primary variable was defined as the increase in 24-h gastric pH median after 1 day of i.v. treatment; the secondary variable was median percentage of time that 24-h gastric pH was <4, as calculated by Hodges-Lehman shift estimators. After 10 days of oral ranitidine treatment, tachyphylaxis was present in all volunteers. Within 1 day of continuous i.v. pantoprazole or i.v. ranitidine administration, 24-h median gastric pH increased from pH 1.45 to pH 3.50 (241%) and from pH 1.50 to pH 2.35 (157%), respectively. I.v. pantoprazole was found to be significantly more effective (p<0.05) than i.v. ranitidine in increasing the 24-h gastric pH after oral ranitidine tachyphylaxis.