Pantoprazole versus omeprazole: influence on meal-stimulated gastric acid secretion

AIMS: To determine the influence of recommended therapeutic doses of pantoprazole and omeprazole on meal-stimulated acid secretion. METHODS: In this double-blind, placebo-controlled, three-period crossover study, 12 healthy male volunteers received 40 mg pantoprazole od, 20 mg omeprazole od or placebo at 08:00 h for 5 days in a randomized order. Meal-stimulated acid secretion was determined by means of a homogenized test meal, and intragastric titration on day 1, 4-6 h, 8-10 h, 16-18 h, and 24-26 h, and on days 3 and 5, 4-6 h after oral drug administration. RESULTS: On day 1 (4-6 h after oral drug administration), meal-stimulated acid secretion was decreased by 36% and 24% after administration of 40 mg pantoprazole or 20 mg omeprazole, respectively. After 3 and 5 days of dosing, the decreases were 88% and 85% with 40 mg pantoprazole, and 70% and 74% with 20 mg omeprazole. At all measuring points during the 5-day dosing periods, 40 mg pantoprazole proved superior to 20 mg omeprazole in inhibiting meal-stimulated gastric acid secretion. The differences were statistically significant for pantoprazole on day 1, 24-26 h after oral drug administration and on day 3 (P = 0.0425 and P = 0.0244, respectively). On day 1, only pantoprazole was significantly better than placebo (P = 0.0210, 4-6 h after dosing; P = 0.0093, 8-10 h after dosing and P = 0.0068, 16-18 h after dosing). CONCLUSION: Pantoprazole 40 mg is significantly more effective than omeprazole 20 mg in inhibiting meal-stimulated acid secretion. In addition, pantoprazole exhibits a more rapid onset of action.     

Effect of nizatidine 300 mg at night and omeprazole 20 mg in the morning on 24-hour intragastric pH and bacterial overgrowth in patients with acute duodenal ulcer

The study investigated the effect of either nocturnal acid suppression by the H₂ antagonist nizatidine 300 mg at night or prolonged acid suppression by the proton-pump inhibitor omeprazole 20 mg in the morning, during four weeks, on intragastric pH profile, occurrence of bacterial growth in gastric fluid and biopsies, and healing rate in 23 patients with an acute duodenal ulcer. The endoscopic healing rate did not differ significantly between the two treatment modalities. The 24-hr acid secretion was significantly more reduced by omeprazole than nizatidine (P<0.002). After treatment by nizatidine and omeprazole, respectively, median 24-hr intragastric pH increased from 1.5 to 1.8 (P<0.01) and from 1.5 to 6.1 (P<0.01), respectively. Nighttime acid inhibition did not differ significantly. The difference in gastric bacterial colonization after either omeprazole or nizatidine did not reach significance. However, median 24-hr pH and the fraction of the day with pH<3 and pH<4 were significantly correlated to bacterial colonization of the gastric fluid (P<0.05).This study was supported by Eli Lilly Nederland B.V.     

Effect of intravenous omeprazole on intragastric pH during intravenous infusion of amino acids

Intravenous amino acids stimulate gastric acid secretion by an unknown mechanism. In patients on parenteral nutrition, this amino acid-induced gastric acid secretion might contribute to the failure of H₂-receptor antagonists to raise intragastric pH above 4.0, a level thought to be needed to prevent stress ulceration. Therefore we studied the effect of single and repeated doses of the H⁺/K⁺-ATPase blocker omeprazole on the intragastric pH during a 3-hr infusion of amino acids in 10 healthy volunteers; 5% glucose was used as a control infusion. Amino acids significantly decreased intragastric pH when compared to glucose infusion (P <0.05). After intravenous administration of 40 mg, 80 mg and 2 × 40 mg omeprazole, this amino acid-induced fall in pH was significantly inhibited (P < 0.01). No advantage of the 80-mg dose over the 40-mg dose could be demonstrated. The repeated dose of 40 mg showed a tendency to higher pH values compared to the single-dose experiments, which reached significance in the amino acid experiments only (P <0.05). Neither during the infusion of amino acids nor the glucose infusion omeprazole was able to continuously raise intragastric pH above 4.0. In conclusion, this study shows that intravenous omeprazole prevents gastric acid stimulation by intravenous amino acids but fails to continuously raise intragastric pH above 4.     

Effect of Preoperative Intravenous Pantoprazole in Elective-Surgery Patients: A Pilot Study

Background This study evaluated the effects of intravenous pantoprazole on gastric volume and acid output in elective-surgical patients. Methods This is a multicenter, randomized, pilot study of adult patients receiving intravenous pantoprazole: 40 mg every 24 h, 40 mg every 12 h (q12h) or 80 mg q12h. The first dose was administered 1 h before general anesthesia for surgery. All gastric fluid was aspirated through a nasogastric tube 1 h before dosing and through the postoperative period. Aspirate volume was recorded; pH and H⁺ concentrations were measured. Result Twenty-six patients were enrolled and 21 were evaluable. Pantoprazole was well tolerated. All regimens decreased gastric acid output and volume, and increased pH within 1 h of dosing. Effects were sustained for up to 12 h following single-dose administration. Conclusions Intravenous pantoprazole administered prior to anesthesia induction may be efficacious for the reduction of gastric volume and acid output, and for pulmonary aspiration prophylaxis in surgical patients.     

Effects of pirenzepine on omeprazole-induced hypergastrinemia and acid suppression in peptic ulcer patients

Omeprazole effectively suppresses acid secretion, resulting in the long-term elevation of intragastric pH and serum gastrin level. Pirenzepine has been reported to inhibit gastrin secretion. This study was carried out to examine the effects of additional pirenzepine treatment on the hypergastrinemia and gastric acid suppression induced by omeprazole. Concentrations of serum gastrin and plasma somatostatin were measured in 28 peptic ulcer patients before treatment, after omeprazole treatment (20 mg/day) for 2 weeks, and after omeprazole and pirenzepine (100 mg/day) treatment for 2 weeks. The acid inhibitory effect of pirenzepine treatment in addition to omeprazole was evaluated by 24-h intragastric pH measurement in six healthy volunteers. Serum gastrin level was increased significantly, to 2.4-fold the pretreatment level, by omeprazole treatment. Additional treatment with pirenzepine suppressed serum gastrin level to 0.6-fold the omeprazole-treatment level. The serum somatostatin level was not altered significantly either by omeprazole treatment or by omeprazole and pirenzepine treatment. In healthy volunteers whose pH 3 holding time on 24-h intragastric pH monitoring was 70% by omeprazole treatment, omeprazole and pirenzepine treatment markedly increased the pH 3 holding time, to 89%. These findings suggest that pirenzepine is useful in reducing the undesirable effects of omeprazole-induced hypergastrinemia, i.e., the excessive trophic effect of omeprazole on the acid-secreting part of the stomach and the overstimulation of acid secretion. The additional pirenzepine treatment is also effective in suppressing acid secretion.     

Intravenous Pantoprazole as Initial Treatment in Patients With Gastroesophageal Reflux Disease and a History of Erosive Esophagitis: A Randomized Clinical Trial

We sought to evaluate safety and efficacy of IV pantoprazole when used as initial therapy in patients with gastroesophageal reflux disease (GERD) and a history of erosive esophagitis (EE) in a double-blind, placebo-controlled, randomized, parallel-group study. Patients were randomized to 7 days of once-daily IV or oral pantoprazole (40 mg) or placebo. Efficacy variables included maximal acid output, basal acid output, and changes from baseline in frequency/severity of GERD symptoms, and frequency of antacid usage. Seventy-eight patients were randomized (n=26/27/25 [IV/oral/placebo]). Mean maximal acid output was 8.4, 6.3, and 20.9 mEq/h for IV or oral pantoprazole, and placebo, respectively. For pantoprazole versus placebo, maximal and basal acid output were significantly lower (P<.001) and there was a numerical trend toward improved GERD and antacid usage. Both treatments were well tolerated. In conclusion, IV/oral pantoprazole were similarly effective in suppressing basal and pentagastrin-stimulated gastric acid secretion in GERD patients with a history of EE.     

Gastric acid control with esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole: a five-way crossover study

OBJECTIVES: Proton pump inhibitors owe their clinical efficacy to their ability to suppress gastric acid production. The objective of this study was to evaluate and compare intragastric pH following standard doses of esomeprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole. METHODS: This randomized, open-label, comparative five-way crossover study evaluated the 24-h intragastric pH profile of oral esomeprazole 40 mg, lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg, and rabeprazole 20 mg once daily in 34 Helicobacter pylori-negative patients aged 18-60 yr with symptoms of gastroesophageal reflux disease. Patients were randomly assigned to one of five treatment sequences and study drug was taken on 5 consecutive mornings 30 minutes prior to a standardized breakfast. A washout period of at least 10 days separated each treatment phase. RESULTS: Thirty-four patients provided evaluable data for all five comparators. The mean number of hours of evaluable pH data was > or =23.75 hours. On day 5, intragastric pH was maintained above 4.0 for a mean of 14.0 h with esomeprazole, 12.1 h with rabeprazole, 11.8 h with omeprazole, 11.5 h with lansoprazole, and 10.1 h with pantoprazole (p < or = 0.001 for differences between esomeprazole and all other comparators). Esomeprazole also provided a significantly higher percentage of patients with an intragastric pH greater than 4.0 for more than 12 h relative to the other proton pump inhibitors (p < 0.05). The frequency of adverse events was similar between treatment groups. CONCLUSIONS: Esomeprazole at the standard dose of 40 mg once daily provided more effective control of gastric acid at steady state than standard doses of lansoprazole, omeprazole, pantoprazole, and rabeprazole in patients with symptoms of gastroesophageal reflux disease.     

Effect of pantoprazole versus other proton pump inhibitors on 24-hour intragastric pH and basal acid output in Zollinger-Ellison syndrome

AIM: In this open prospective study, the efficacy of pantoprazole in reducing gastric acid secretion in Zollinger-Ellison syndrome patients was compared to that obtained previously with other proton pump inhibitors.METHODS: Eleven male patients previously treated with omeprazole (n=7, mean dosage: 63 mg/day; range: 20-100 mg/day) or lansoprazole (n=4, mean dosage: 75 mg/day; range: 30-120 mg/day) were included. These patients underwent a 24-hour intragastric pH-metry, measurement of basal acid output and of serum gastrin first while receiving their usual therapy and second after 7 to 10 days of pantoprazole treatment at a mean dosage of 116 mg/day (range: 40-200 mg/day). Basal acid output was evaluated after each intragastric pH-metry, one hour before the next intake of proton pump inhibitor and a serum gastrin curve was determined according to 9 fixed time points.RESULTS: One patient dropped out before the second intragastric pH-metry due to an adverse event (varicella) unrelated to pantoprazole and was reinvestigated thereafter. The median 24-h intragastric pH with pantoprazole was not significantly different than that with the other proton pump inhibitors (5.3 versus 4.6, respectively; P=0.90). Neither the median basal acid output values nor the median serum gastrin levels were significantly different between pantoprazole and the other proton pump inhibitors.CONCLUSION: In these patients with the Zollinger-Ellison syndrome, pantoprazole was well tolerated and equally effective to the other proton pump inhibitors in terms of antisecretory potency.     

Effects of pantoprazole, a novel H+/K+-ATPase inhibitor, on duodenal ulcerogenic and healing responses in rats: a comparative study with omeprazole and lansoprazole

BACKGROUND: Pantoprazole, 2-[(2-pyridylmethyl) sulphinyl] benzimidazole, is a new substituted benzimidazole that inhibits the parietal cell H+/K+-ATPase. METHODS: In the present study, the anti-secretory and anti-ulcer activities of pantoprazole were compared with those of omeprazole and lansoprazole in rats. RESULTS: Pantoprazole (0.3-3 mg/kg, p.o.) as well as omeprazole (1-10 mg/kg, p.o.) and lansoprazole (1-10 mg/kg, p.o.) dose-dependently decreased both basal acid secretion in pylorus-ligated rats and the stimulated acid secretion induced by mepirizole in acute fistula rats, and the effects of pantoprazole were more potent than those of omeprazole and lansoprazole, the ED50 values for the stimulated acid secretion being 0.8, 2.0 and 1.2 mg/kg, respectively. Neither of these drugs had any effect on duodenal HCO3- secretion. These pump inhibitors prevented the development of duodenal lesions in response to mepirizole in a dose-related manner, the ED50 values for pantoprazole, omeprazole and lansoprazole being 0.4, 2.0 and 1.3 mg/kg, respectively. Likewise, pantoprazole showed the healing promoting action on chronic duodenal ulcers induced by acetic acid, and this effect was also more potent when compared to omeprazole or lansoprazole. CONCLUSIONS: We conclude that pantoprazole exhibited both anti-ulcer and healing promoting effects on duodenal ulcers in rats, and the effects may be attributable to its potent anti-secretory action. Other pump inhibitors such as omeprazole and lansoprazole were almost equally effective as pantoprazole, yet this drug was most potent on the basis of ED50 values.     

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

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.     

Effect of repeated boluses of intravenous omeprazole and primed infusions of ranitidine on 24-hour intragastric pH in healthy human subjects

The aim of this study was to identify dosage regimens using intravenous omeprazole and ranitidine that would elevate and consistently maintain intragastric pH>6 in the first 24 hr of therapy. In 19 healthy, fasting human subjects using continuous 24-hr gastric pH-metry, we studied two dosages of primed infusions of ranitidine (50 mg bolus followed by infusion of either 3 or 6 mg/kg body wt/24 hr) and six regimens of intravenous omeprazole (80–200 mg in 24 hr in two to five boluses). Only the two ranitidine infusions and high doses of omeprazole (≥160 mg/day as four or five boluses) raised the intragastric median pH above 5.4. There was no significant difference in the median intragastric pH after high dose ranitidine and high doses of omeprazole. Considerable interindividual variation in intragastric pH was observed after omeprazole therapy. The percentage of intragastric pH>6.0 during the 24-hr study was lower after omeprazole (35–42%) than after high-dose ranitidine (58%). We conclude that it is possible to raise intragastric pH>6.0 by use of either primed ranitidine infusion or by repeated boluses of omeprazole. However, maintenance of this high pH in the first 24 hr is difficult with both, more so with omeprazole.     

Effects of NC-1300-B,A new benzimidazole derivative,on hog gastric H+, K+-ATPase,gastric acid secretion and HCl-ethanol-induced gastric lesions in rats

This study was designed to determine the effect of a newly synthesized benzimidazole derivative NC-1300-B on H⁺,K⁺ -ATPase (proton pump) in the hog gastric mucosa and on the basal gastric acid secretion and necrotizing agent-induced gastric lesions in rats. NC-1300-B inhibited the proton pump in a concentration-dependent manner and concentrations which inhibited the enzyme activity by 50% were 4.4×10^–6 M at pH 6.0 and 3.1 ×10^–5 M at pH 7.4. NC-1300-B administered orally or intraperitoneally 0.5 hr before ligating the pylorus inhibited the gastric acid secretion in a dose-dependent manner. The ED₅₀ values (doses which inhibit acid output or lesion formation by 50%) for acid secretion were 11.5 and 11.0 mg/kg with oral and intraperitoneal administration, respectively. The antisecretory effect in a dose of 100 mg/kg persisted for up to 72 hr. NC-1300-B administered orally or intraperitoneally 0.5 hr before HCl-ethanol administration protected against damage of the gastric mucosa in a dose-dependent manner. The ED₅₀ values for lesion formation were 13.3 and 23.0 mg/kg with oral and intraperitoneal administration, respectively. This protection with an oral dose of 100 mg/kg persisted for up to 72 hr. While pretreatment with 5 mg/kg of indomethacin given subcutaneously did not appreciably reverse the NC-1300-B protection, the pretreatment with 10 mg/kg of N-ethylmaleimide given subcutaneously potently reversed the NC-1300-B protection. NC-1300-B administered intragastrically at 30 mg/kg significantly inhibited the amplitude of gastric contraction for 50 min after intragastric administration. These effects of NC-1300-B on gastric secretion and lesion formation are much the same as those of the established proton pump inhibitor omeprazole, except for the short duration of the action of omeprazole (<24 hr).     

Maintenance oral pantoprazole therapy is effective for patients with Zollinger-Ellison syndrome and idiopathic hypersecretion

OBJECTIVE: Maintenance proton pump inhibitor (PPI) therapy is effective for gastric acid hypersecretory states, although data with pantoprazole are limited. The aim of this study was to evaluate the safety and efficacy of long term p.o. pantoprazole in individuals with hypersecretion. METHODS: All subjects had Zollinger-Ellison syndrome or idiopathic hypersecretion. Baseline acid output was measured in the presence of prior maintenance antisecretory therapy before pantoprazole exposure. The starting dose was 40 mg b.i.d. in most cases, and the dose was adjusted to document control within the first 2 wk of therapy. The maximal allowable dose was 240 mg daily. Acid output was measured on day 28 and then quarterly from month 3. The primary efficacy endpoint was documented control of acid secretion at 6 months, i.e., acid output in the last 1 h before the next dose of therapy of <10 mEq/h (<5 mEq/h in subjects with prior acid-reducing surgery). RESULTS: A total of 26 subjects had Zollinger-Ellison syndrome (six with multiple endocrine neoplasia syndrome type 1) and nine had idiopathic hypersecretion. Pre-enrollment therapy included omeprazole in 27 subjects and lansoprazole in eight, and 82.4% of subjects were controlled on their prior regimens. With upward dose titration, acid output was controlled in all subjects by day 10 and in all but two (6%) at the 6-month time point. Median acid secretion on therapy at 6 months was <2 mEq/h (mean 2.2 mEq/h; range 0-10.5 mEq/h) at a dose of 40 mg b.i.d. for 24 subjects, 80 mg b.i.d. for seven subjects, and 120 mg b.i.d. for two subjects. During the course of the study, five subjects required doses of 240 mg daily. Pantoprazole was generally well tolerated. No cases of anterior optic ischemic neuropathy occurred. Five subjects died during follow-up, all because of events unrelated to the study drug. CONCLUSIONS: Maintenance p.o. pantoprazole therapy at a dose of 80-240 mg/day in divided doses was both effective and generally well tolerated for patients with Zollinger-Ellison syndrome and idiopathic hypersecretion.     

Effect of omeprazole on plasma zinc levels after oral zinc administration.

BACKGROUND: The intestines are the major site of zinc absorption and excretion. Reduced gastric acid secretion and elevated gastric pH is an important factor affecting intestinal mineral absorption. METHODS: Gastric pH and volume, and basal and maximal acid outputs were measured in 14 healthy volunteers. Plasma zinc levels were then measured at baseline and 1, 2, 3 and 4 hours after oral administration of 300 mg zinc sulfate. The experiment was repeated after omeprazole administration (60 mg/day orally) for 7 days. RESULTS: Omeprazole administration significantly increased fasting gastric pH (5.5 versus 2.4; p < 0.001). Mean basal gastric acid output (1.6 vs 8.0 mEq/h; p < 0.001) and maximal acid output (20.6 vs 106.6 mEq/h; p < 0.001) decreased after omeprazole administration. Zinc absorption decreased after omeprazole administration (141 [34] mg/dL/h) compared with pre-omeprazole values (245 [35]; p < 0.01). CONCLUSION: Suppression of gastric acid secretion by omeprazole reduces intestinal absorption of zinc.     

Comparison of omeprazole and ranitidine in treatment of refractory gastroesophageal reflux disease in patients with gastric acid hypersecretion

Secretion of gastric acid and volume, serum gastrin concentration, and ambulatory 24-hr esophageal pH monitoring were evaluated prospectively in 12 patients with idiopathic gastric acid hypersecretion (basal acid output greater than 10.0 meq/hr) undergoing treatment for refractory chronic long-standing pyrosis. Treatment lasted six months and consisted of three months of ranitidine (mean 2150 mg/day, range 1200–3000 mg/day), followed by three months of omeprazole (mean 33 mg/day, range 20–60 mg/day). Both ranitidine and omeprazole significantly reduced gastric acid output (P<0.001) and gastric volume output (P<0.001) compared to a basal evaluation and resulted in complete disappearance of pyrosis. Total reflux time (percent 24 hr intraesophageal pH less than 4) was significantly reduced by ranitidine (P<0.02) and omeprazole (P<0.001) compared to basal evaluation; however, the effects of omeprazole were significantly greater than ranitidine (P<0.05). Omeprazole caused a significant increase in serum gastrin concentration compared to both basal and ranitidine (P<0.05). Endoscopically documented erosive esophagitis was present in nine of the 12 patients, and seven of the 12 patients had Barrett's epithelium. All 12 patients had complete resolution of pyrosis and healed esophagitis by six months, but no significant endoscopic regression was observed in the extent of Barrett's epithelium. No side effects occurred with these high doses of ranitidine or omeprazole. These results indicate that high-dose ranitidine and omeprazole are effective therapy for refractory gastroesophageal reflux disease. However, with omeprazole, total reflux times are reduced more than with ranitidine, often into the normal range. That marked reduction of gastric acid secretion with omeprazole, which greatly reduces total reflux times, accounts for the significant elevation of serum gastrin concentration seen during omeprazole therapy.     

Replacement of oral proton pump inhibitors with intravenous pantoprazole to effectively control gastric acid hypersecretion in patients with Zollinger-Ellison syndrome

OBJECTIVES: In patients with Zollinger-Ellison syndrome (ZES) or other conditions requiring oral doses of proton pump inhibitors, it frequently becomes necessary to use parenterally administered gastric acid inhibitors. However, i.v. histamine-2 receptor antagonists are not effective at usual doses and lose their effectiveness because of tachyphlaxis. With the approval in the United States of i.v. pantoprazole, a substituted benzimidazole available in i.v. formulation, it will become possible to acutely manage gastric acid secretion in the acute care setting of a hospital. This study was developed to monitor the safety and establish the efficacy of i.v. pantoprazole as an alternative to oral proton pump inhibitors for the control of gastric acid hypersecretion in patients with ZES. METHODS: The efficacy of replacing oral PPI therapy with i.v. pantoprazole was evaluated in 14 ZES patients. After study enrollment, patients taking their current doses of oral PPI (omeprazole or lansoprazole) were switched to pantoprazole i.v. for 6 days during an 8-day inpatient period in the clinical research center. Effective control was defined as an acid output (AO) of < 10 mEq/h (< 5 mEq/h in patients with prior gastric acid-reducing surgery). RESULTS: The mean age of the 14 patients enrolled in the study was 52.4 yr (range = 38-67). Mean basal AO was 0.55 +/- 0.32 mEq/h and mean fasting gastrin was 1089 pg/ml (range = 36-3720). Four patients were also diagnosed with the multiple endocrine neoplasia type I syndrome, nine were male, and two had previously undergone acid-reducing surgery. Before study enrollment, gastric acid hypersecretion was controlled in nine of 14 patients with omeprazole (20-200 mg daily) and five of 14 with lansoprazole (30-210 mg daily). In the oral phase of the study all patients had adequate control of gastric acid secretion, with a mean AO of 0.55 +/- 0.32 mEq/h (mean +/- SEM). Thereafter, 80 mg of i.v. pantoprazole was administered b.i.d. for 7 days by a brief (15 min) infusion and the dose was titrated upward to a predetermined maximum of 240 mg/24 h to control AO. A dose of 80 mg b.i.d. of i.v. pantoprazole controlled AO in 13 of 14 of the patients (93%) for the duration of the study (p > 0.05 compared to baseline values for all timepoints). One sporadic ZES patient (oral control value = 0.65 mEq/h on 100 mg of omeprazole b.i.d. p.o.) was not controlled with 80 mg of i.v. pantoprazole b.i.d. and dosage was titrated upward to 120 mg b.i.d. after day 2. CONCLUSIONS: There were no serious adverse events observed. Intravenous pantoprazole provides gastric acid secretory control that is equivalent to the acid suppression observed with oral proton pump inhibitors. Most ZES patients (93%) maintained effective control of AO previously established with oral PPIs when switched to 80 mg of i.v. pantoprazole b.i.d.; however, for difficult-to-control patients, doses > 80 mg b.i.d. may be required.     

泮托拉唑钠粉针剂治疗上消化道出血疗效观察

目的　评价泮托拉唑钠 (诺森 )粉针剂对消化性溃疡所致的上消化道出血的疗效和安全性 ,并与奥美拉唑 (洛赛克 )粉针剂作对照。方法　选择消化性溃疡出血患者 90例 ,泮托拉唑治疗组 60例 ,其中胃溃疡 (GU) 2 4例 ,十二指肠球部溃疡 (DU) 33例 ,糜烂性胃炎 3例。奥美拉唑对照组 30例 ,其中GU 9例 ,DU 1 6例 ,糜烂性胃炎 5例。治疗方法 :分别用泮托拉唑或奥美拉唑 80mg加入 5 %葡萄糖液 2 50ml内 ,静脉滴注 (30～ 60min) ,1次 /d ,共 5d。观察生命体征与出血情况的改变。结果　两组出血情况差异无显著性 (P >0 .0 5)。治疗后 3d内泮托拉唑组有 51例止血 (85 % ) ,奥美拉唑组有 2 4例止血 (80 % ) ;4～ 5d内止血分别为 7例 (1 1 .7% )和 5例 (1 6 .7% )。止血显效率 ,泮托拉唑组为 85 % ,奥美拉唑组为 80 % ,治疗总有效率两组均为 96 .7%。两组各有 1例出现恶心症状 ,不良反应发生率分别为1 .7%和 3 .4%。结论　泮托拉唑钠粉针剂是治疗消化性溃疡出血安全、有效的药物     

Measurement of postprandial changes in urine acid output to detect changes of gastric acid secretion after proton pump inhibitors in children

Acid inhibition after proton pump inhibitors in children is variable, and to measure it by a noninvasive method may help to tailor treatment. To study gastric acid inhibition after a single dose of PPI, by measuring urinary acid output (UAO), which decreases as parietal cells release acid into the stomach during a meal, we performed a prolonged pH monitoring in 31 children (age range 3–16 yrs). Esophageal and intragastric pH was recorded for 24 hr and for 5 more hr after a single dose of PPI or placebo. Urine was collected early in the morning, and 1 hr after a test meal. Intragastric and urinary parameters were analyzed for 5 hr after PPI and compared to the same 5 hr at baseline. After PPI, median gastric pH significantly increased, and median UAO became significantly smaller (–0.31 vs. –1.40 at baseline; P = 0.002) but was unchanged after placebo. Inhibition of gastric acid induced by PPI can be detected by changes in UAO and its determination may be useful to monitor the PPI effect.     

Twenty-four-hour intragastric pH patterns in ICU patients on ranitidine

Thirty critically ill patients with mixed diagnoses underwent continuous intragastric pH monitoring for 72 hr while confined to a shock/trauma intensive care unit. The first 24 hr were monitored under no specific acid-suppressing therapy (placebo control). During the second and third consecutive 24-hr periods, patients received continuous infusion of intravenous ranitidine in the dose of 6.25 mg/hr and 12.5 mg/hr, respectively. Results of the placebo-control 24-hr study revealed that one third (N=10) of the patients were gastric acid hyposecretors (24-hr median intragastric pH values above pH 4.0). In the normosecreting group (N=20), both ranitidine schedules significantly elevated 24-hr median pH values, when compared to placebo (placebo 24-hr median intragastric pH 1.75; ranitidine 6.25 mg/hr 24-hr median intragastric pH 4.625,P<0.0001; ranitidine 12.5 mg/hr 24-hr median intragastric pH 6.29,P=0.0099). Five patients (18%) failed to adequately respond to the ranitidine 12.5 mg/hr dose (24-hr median intragastric pH<4.0). These findings suggest that a significant percentage of intensive care unit patients are not in need of acid-suppressing therapy as prophylaxis against stress-induced ulceration. Conversely, other patients may require more intensive acid-suppressing regimens because of failure to respond to high dose H₂-antagonist therapy.     

Effect of Omeprazole 40 mg Once Daily on Intraduodenal and Intragastric pH in H. Pylori-Negative Healthy Subjects

There is a lack of information about the effectof omeprazole or other antisecretory drugs onintraduodenal pH. Aim of the study was to document thevariation over time of intraduodenal pH during a 24-hr period and to simultaneously study the effectof omeprazole 40 mg once daily on intragastric andintraduodenal pH in healthy H. pylori-negative subjects.In a randomized, placebo-controlled study, eight subjects (five women, three men, mean age 22.7years) received oral 40 mg omeprazole or placebo oncedaily for eight days. On day 7, intragastric andintraduodenal pH was measured continuously for 24 hr, using two miniature glass-membrane electrodesplaced in the stomach (fundus) and in the distal thirdof the duodenum. The 24-hr median intraduodenal pH was5.95 with placebo and 5.85 with omeprazole. Median intragastric pH was 1.68 without and 4.93 withomeprazole. During omeprazole therapy, intragastric pHfell below 4.0 in five of eight subjects. In the 2- and3-hr postprandial periods, the percentage of time with pH < 5 was significantly reducedwith omeprazole. In healthy subjects, 24-hr median andpostprandial pH in the distal part of the duodenum waslower than previously thought. Omeprazole significantly reduced the percentage of time with pH < 5postprandially. At night, intragastric pH fell below 4.0with omeprazole 40 mg once daily. Omeprazole does notchange 24-hr median intraduodenal pHsignificantly.