小剂量奥美拉唑镁肠溶片对健康成人24小时胃内pH的影响

目的　奥美拉唑具有强大的抑制胃酸分泌的作用 ,常用剂量为 2 0mg。因此 ,探讨小剂量奥美拉唑镁肠溶片 (洛赛克MUPS ,1 0mg)对健康成人 2 4h胃内 pH变化的影响。 方法　利用Digitrap perMKⅢ动态 pH监测仪观察 1 2例健康志愿者 2 4h胃内pH变化节律 ,次日晨 8时口服奥美拉唑镁肠溶片 1 0mg ,并复查 2 4h胃内 pH。经过 1周清洗期后 ,其中 1 1例受试者再予以奥美拉唑镁肠溶片 1 0mg ,每日 1次 ,连续 6d ,并于第 6天复查 2 4h胃内pH。 结果　奥美拉唑镁肠溶片 1 0mg顿服后 ,2 4h胃内 pH中位值由 1 .0 0升高至 1 .2 0 ,2 4h胃内平均pH值、pH >3总时间百分比、pH >4总时间百分比及pH >5总时间百分比分别由 1 .56± 0 .34 ,(1 8.44± 7.55) % ,(1 2 .0 5± 6 .1 0 ) % ,(6 .89± 4 .40 ) %升高至 2 .1 8± 0 .65(P <0 .0 1 ) ,(34 .40± 1 2 .73) % (P <0 .0 1 ) ,(2 3 .58± 1 0 .59) % (P <0 .0 1 )及 (1 3 .58± 8.36) % (P <0 .0 5)。奥美拉唑镁肠溶片 1 0mg ,每日 1次 ,连续 6d后 ,2 4h胃内 pH中位值升高至 3 .2 0 ,2 4h胃内平均 pH值、pH >3总时间百分比、pH >4总时间百分比及 pH >5总时间百分比分别升高至 4 .30± 1 .61 ,(59.2 1± 2 1 .37) % ,(48.1 3± 2 3 .2 4 ) %及 (36 .85± 2 2 .62 ) % ,均显     

静脉滴注潘妥拉唑对健康成人24小时胃内pH变化的影响

目的探讨质子泵阻滞剂潘妥拉唑对健康成人24h胃内pH变化的影响.方法利用DigitrapperMKⅢ动态pH监测仪观察10名健康志愿者24h胃内pH变化节律,1周后,分别于晨8时静脉滴注潘妥拉唑80mg,连续2d,并于第2天给药后立即进行24h胃内pH监测.结果健康成人24h胃内pH平均值为2.21±0.86,pH＞4总时间百分比为(15.75±13.60)%,24h胃内pH变化曲线下面积为1.90×105±0.80×105.静脉滴注潘妥拉唑后,24h胃内pH平均值、pH＞4总时间百分比、24h胃内pH变化曲线下面积分别升至7.18±1.06、(93.41±8.43)%及6.20×105±0.90×105(P＜0.01).结论正常人24h胃内pH变化节律证实,潘妥拉唑有较强的抑制胃酸分泌作用.     

Effect of intravenous and oral omeprazole on 24-hour intragastric acidity in duodenal ulcer patients.

Nine patients with duodenal ulcer were on separate occasions given omeprazole, 20 mg orally, 10 mg intravenously (IV), and 40 mg IV once daily for 5 days. On day 1, the median reduction of 24-hour intragastric acidity was 42.2% for the 20-mg oral dose and 54.8% and 88.4% for the two IV doses, respectively, but the between-patient variability was considerable for all three doses. On day 5, the degree of reduction had increased for all three doses to a median value of 99.9% for the 20-mg oral dose and 95.7% and 99.9% for the two IV doses, respectively. Plasma omeprazole concentrations increased significantly from day 1 to day 5 only for the 20-mg oral and 40-mg IV doses. Thus, the increased pharmacological effect of omeprazole during repeated once daily administration can only partly be explained by increased plasma concentrations, suggesting that some additional factor(s) must influence the degree of reduction of 24-hour intragastric acidity. Thus, when determining the optimal dose of omeprazole for acid inhibition, the route and duration of administration must be taken into consideration; after 5 days of once-daily administration of doses as low as 10 mg IV and 20 mg orally are effective and dependable in reducing 24-hour intragastric acidity in patients with duodenal ulcer. However, a daily dose of 40 mg IV omeprazole is not sufficient to keep intragastric pH above 4 in all patients during the first day of treatment.     

Effect of repeated injection and continuous infusion of omeprazole and ranitidine on intragastric pH over 72 hours

OBJECTIVE: In healthy subjects and patients with bleeding peptic ulcers, ranitidine and omeprazole, given parenterally, achieve high intragastric pH values on the first day of therapy. However, data on the antisecretory effect beyond the first 24 h is scanty. In addition, the superiority of either infusion or injection of omeprazole remains unproven. Thus, we have compared the antisecretory effect of high dose omeprazole and ranitidine infusion and injection over the critical first 72 h. METHODS: A total of 34 healthy volunteers were randomized into a double-blind crossover 72 h intragastric pH-metry study (data compared: median pH, percentage of time with pH >4 and pH >6). Omeprazole-infusion: initial bolus of 80 mg + 8 mg/h; omeprazole-injection: initial bolus of 80 mg + 40 mg/6 h; Ranitidine-infusion: initial bolus of 50 mg + 0.25 mg/kg/h; ranitidine-injection: 100 mg/6 h. RESULTS: Omeprazole-infusion versus ranitidine-infusion: on day 1: median pH 6.1 vs 5.1 (p = 0.01) and 95% vs 70% was pH >4 (p < 0.01); on day 2: median pH 6.2 vs 3.2 (p < 0.01); and 100% vs 38% was pH >4 (p < 0.01); on day 3: median pH 6.3 vs 2.7 (p < 0.01); 100% vs 26% was pH >4 (p < 0.01). Injections of both drugs were significantly less effective than the infusions on day 1. Thereafter, omeprazole injection was almost as effective as omeprazole infusion, whereas ranitidine injection and infusion were equally effective. CONCLUSION: Our study shows, for the first time, that omeprazole infusion was significantly superior to all other regimens by having a high median pH >6 on each day. The tolerance effect of ranitidine, however, led to a rapid loss of antisecretory activity on days 2 and 3, rendering it inappropriate for situations in which high intragastric pH-levels appear to be essential.     

Intravenous omeprazole: effect on 24-hour intragastric pH in duodenal ulcer patients

This study was aimed to identify an intravenous dosage regime of omeprazole which would sufficiently suppress acid secretion to maintain intragastric pH greater than 4 continuously. Thirteen duodenal ulcer patients in remission received omeprazole in daily intravenous doses ranging from 40 to 200 mg. Doses were successively increased as dictated by patient response. The intragastric pH data indicated that omeprazole given in twice or thrice daily regimes in total intravenous amounts of 200, 160 and 160 mg over a consecutive 3-day period markedly inhibited acid secretion and maintained intragastric pH greater than 4 with few and short-term exceptions.     

Effect of intravenous application of esomeprazole 40 mg versus pantoprazole 40 mg on 24-hour intragastric pH in healthy adults

BACKGROUND: It has been demonstrated that therapy with proton pump inhibitors reduces recurrence of bleeding following initial endoscopic treatment of bleeding peptic ulcers. AIM: This study compared the effects of esomeprazole 40 mg and pantoprazole 40 mg on intragastric acid control. Both substances were administered intravenously as 15-min infusion and as bolus injection. METHODS: Healthy men and women volunteers were enrolled in this single-center, open, randomized, three-way crossover study. After administration of esomeprazole 40 mg and pantoprazole 40 mg intravenously as 15-min infusion, and pantoprazole 40 mg intravenously as bolus injection, continuous 24-h intragastric pH monitoring was carried out. RESULTS: pH data were available for 21 Helicobacter pylori-negative and seven H. pylori-positive volunteers. In H. pylori-negative volunteers, esomeprazole 40 mg intravenously resulted in 11.8 h with an intragastric pH>4 compared with 5.6 h for pantoprazole 40 mg intravenously as infusion (P<0.0001), and 7.2 h for pantoprazole 40 mg intravenously as bolus injection (P<0.001). During the first 6 h of administration, the corresponding values were 3.4, 1.1 (P<0.000001), and 2.1 h (P<0.001), respectively. CONCLUSIONS: In H. pylori-negative patients, a single dose of esomeprazole 40 mg intravenously provides an intragastric acid control that is faster and more pronounced than administration of pantoprazole 40 mg intravenously.     

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.     

Control of gastric pH with cimetidine: boluses versus primed infusions

Previous studies suggest that antacids are more effective than intravenous cimetidine in maintaining the gastric pH above 4.0 in acutely ill patients. We hypothesized that this was because blood levels of cimetidine are not sustained at therapeutic levels with the bolus doses. The purpose of this study was to compare gastric pH and serum cimetidine levels when cimetidine was administered as bolus versus infusion. We studied 23 acutely ill patients who received intravenous cimetidine given as boluses and primed infusions. The gastric pH could be maintained above 4.0 with infusions of up to 50 mg/h (1200 mg/day) in 20 patients, compared with only 5 patients with bolus administrations of up to 300 mg every 6 h (1200 mg/day). The differences in ability to maintain the gastric pH above 4.0 were entirely due to the reduced ability of bolus infusion to maintain an adequate serum level. Neither technique could maintain the pH above 4.0 in 3 patients, all of whom had received cimetidine recently. A gastric pH greater than 4.0 correlated directly with a therapeutic serum cimetidine level. We conclude that infusions of cimetidine are better able to sustain therapeutic blood levels and, therefore, are superior to bolus cimetidine in maintaining gastric pH above 4.0. Some patients, however, may not respond to cimetidine even if therapeutic levels are achieved and may require supplemental antacids.     

Effect of cimetidine on 24-hour intragastric acidity in normal subjects.

The effect of H2-receptor blockade on intragastric acidity was studied in nine normal males. The pH of their gastric contents was measured at hourly daytime and two hourly nighttime intervals for 48 hours. The subjects ate identical meals, drank identical volumes of fluid, and smoked the same number of cigarettes during the two study days. Their physical activity was unrestricted in a ward environment. Blood cimetidine and plasma gastrin were measured in serial blood samples. The nine subjects were treated in random sequence with cimetidine 0-8-1-0 g on one day and placebo capsules on the other. The drug was given in four divided doses: four subjects received it before, and five after, the three main meals. All took the fourth dose at bedtime. Replicate studies in an additional subject given placebo on both study days showed good reproducibility (r=0-80, P less than 0-01). Cimetidine therapy decreased intragastric acidity in all nine subjects. The decrease was similar in the two groups taking the drug before or after meals, mean 24 h intragastric hydrogen ion activity being lowered by 70 and 72% respectively. Nocturnal anacidity was recorded in only two of 45 samples. Administration of cimetidine before meals produced earlier and higher drug blood levels than post-prandial medication, but when it was taken after food the blood levels were highest at the time when the buffer capacity of the food was waning. Blood concentrations of cimetidine exceeded the secretory IC50 level for most of the time between doses. The results show that cimetidine 0-8-1-0 g/day in four divided doses produces a striking and consistent decrease of intragastric acidity. Although variation in the timing of the dose in relation to meals did not affect the decrease of acidity, the absorption data suggest that patients should take the drug after meals.     

Effect of omeprazole on nocturnal intragastric pH in cirrhotics with inadequate antisecretory response to ranitidine

Failure of acid suppression by H2-receptor antagonists has been observed, and recently we have found a higher frequency of patients with inadequate antisecretory response among patients with cirrhosis of the liver. In the present study comprising 16 cirrhotics with inadequate antisecretory response to 300 mg of ranitidine, we tested the effect of 40 mg omeprazole. Nighttime intragastric pH was continuously monitored, and a rise in the intragastric pH above 4.0 for more than 6 h following the oral dose at 18.00 h was considered as response. The median pH profile during the omeprazole treatment was significantly higher than with ranitidine (p less than or equal to 0.001). In contrast to 300 mg ranitidine, which despite sufficient plasma levels 2 and 4 h after intake (762 +/- 431 and 802 +/- 668 ng/ml) resulted in a rise in the nighttime intragastric pH above 4 only for 1.8 +/- 1.7 h, after omeprazole for at least 5 days, the intragastric pH was for 10.1 +/- 2.4 of 12 h above 4 during the night (p less than 0.001). The omeprazole plasma levels were 611 +/- 323 and 881 +/- 533 ng/ml after 2 and 4 h. The data obtained with intragastric pH monitoring indicate that the H+K(+)-ATPase inhibitor omeprazole is able to overcome the H2-blocker resistance in cirrhotics.     

24-hour intragastric acidity and plasma gastrin during long-term treatment with omeprazole or ranitidine in patients with reflux esophagitis

The reduction in intragastric acidity and the subsequent increase in plasma gastrin were compared during long-term treatment with either omeprazole or ranitidine in 19 patients with erosive reflux esophagitis. The patients received 40 mg omeprazole in the morning or 300 mg ranitidine twice daily. After healing, half the dose was given as maintenance treatment for 1 year. Intragastric acidity and plasma gastrin were measured 24 h before entry and monthly with the high dose and after 1, 6, and 12 months with the low dose. Omeprazole reduced intragastric acidity more effectively than ranitidine (p less than 0.001). This difference in efficacy was more pronounced during the daytime. Plasma gastrin increased more after omeprazole than after ranitidine (p less than 0.01), and both drugs showed a normal postprandial response and approached fasting levels before the next dose. During long-term treatment with 20 mg omeprazole in the morning no progressive alterations were observed in 24-h intragastric acidity or plasma gastrin.     

Repeated intravenous bolus injections of omeprazole: effects on 24-hour intragastric pH, serum gastrin, and serum pepsinogen A and C

We determined the effect of four times daily dosing with intravenous omeprazole on 24-h intragastric acidity, serum gastrin, and serum pepsinogen A and C in 10 fasting subjects (median age, 23.5 years). Two dose regimens (80-20-20-20 mg and 80-40-40-40 mg) were compared in a randomized placebo-controlled crossover study. Intragastric pH was continuously monitored during 24 h, using combined glass electrodes, and blood samples were taken every 6 h. Repeated boluses of omeprazole every 6 h significantly increased (p less than 0.01) the median 24-h intragastric pH compared with placebo (median pH, 3.7 (140 mg/day), 4.3 (200 mg/day), and 1.4 (placebo)) but failed to continuously raise pH levels above 4.0 in 8 (140 mg/day) or 9 (200 mg/day) of 10 subjects. No advantage of the 200-mg dose over the 140-mg dose was demonstrated. A cumulative effect of intravenous omeprazole was shown after repeated boluses but also a marked interindividual variation in response, which was correlated with the omeprazole area under the plasma concentration time curve. A significant elevation of serum gastrin coincided with the increased pH levels, which was followed after 12-18 h by a significant increase of both serum pepsinogens.     

Efficacy of primed infusions with high dose ranitidine and omeprazole to maintain high intragastric pH in patients with peptic ulcer bleeding: a prospective randomised controlled study.

BACKGROUND: In healthy subjects, continuous infusions of high dose ranitidine and omeprazole produce high intragastric pH values. AIM: To test the hypothesis that both drugs also maintain high intragastric pH values in patients with bleeding ulcers. PATIENTS AND METHODS: In two parallel studies, 20 patients with bleeding duodenal ulcers and 20 patients with bleeding gastric ulcers were randomly assigned to receive either ranitidine (0.25 mg/kg/hour after a bolus of 50 mg) or omeprazole (8 mg/hour after a bolus of 80 mg) for 24 hours. Intragastric pH was continuously recorded with a glass electrode placed 5 cm below the cardia. RESULTS: Both drugs rapidly raised the intragastric pH above 6. During the second 12 hour period, however, the percentage of time spent below a pH of 6 was 0.15% with omeprazole and 20.1% with ranitidine (p = 0.0015) in patients with duodenal ulcer; in patients with gastric ulcer it was 0.1% with omeprazole and 46.1% with ranitidine (p = 0.002). CONCLUSIONS: Primed infusions of omeprazole after a bolus produced consistently high intragastric pH values in patients with bleeding peptic ulcers, whereas primed infusions with ranitidine were less effective during the second half of a 24 hour treatment course. This loss of effectiveness may be due to tolerance.     

Effect of esomeprazole 40 mg vs omeprazole 40 mg on 24-hour intragastric pH in patients with symptoms of gastroesophageal reflux disease

Maintenance of intragastric pH > 4 is vital for effective management of gastroesophageal reflux disease (GERD). Esomeprazole 40 mg, the first proton pump inhibitor developed as an optical isomer, demonstrates improved acid inhibition over omeprazole 20 mg. Our aim was to compare esomeprazole 40 mg with omeprazole 40 mg, once-daily, on intragastric acidity in patients with symptoms of GERD. In this open-label, crossover study, 130 patients with symptoms of GERD received esomeprazole 40 mg or omeprazole 40 mg once-daily for five days. The 24-hr intragastric pH was monitored on days 1 and 5 of each treatment period. The mean percentage of the 24-hr period with intragastric pH > 4 was significantly greater (P < 0.001) with esomeprazole 40 mg than with omeprazole 40 mg on days 1 (48.6% vs 40.6%) and 5 (68.4% vs 62.0%). Interpatient variability was significantly less with esomeprazole than omeprazole. Esomeprazole was well tolerated. In conclusion, esomeprazole 40 mg provides more effective acid control than twice the standard dose of omeprazole.     

Effects of ranitidine 150 mg four times a day on 24-hour intragastric acidity and 24-hour plasma gastrin concentration

Twenty-four-hour integrated intragastric acidity and 24-hr integrated plasma gastrin concentration was measured twice in 23 healthy male volunteers on the seventh day of oral dosing with placebo or ranitidine 150 mg four times a day. The study was a randomized, double-blind, placebo-controlled, two-way crossover investigation. The mean integrated 24-hr intragastric acidity during dosing with ranitidine 150 mg four times a day decreased to 32% of the placebo value (placebo 825 mmol/hr/liter; ranitidine 265 mmol/hr/liter). The mean integrated 24-hr plasma gastrin concentration during dosing with ranitidine 150 mg four times a day was 904 pmol/hr/liter compared with placebo (410 pmol/hr/liter)—an increase of 122%. The median number of hours of pH>3 during dosing with placebo and with ranitidine 150 mg four times a day were 5 and 11 hr, respectively. Ranitidine 150 mg four times a day caused a significant decrease of mean integrated intragastric acidity for each meal-related interval and also during the night.     

三种奥美拉唑胶囊健康人的生物利用度及其对胃内24小时pH值的影响

目的 比较３种奥美拉唑产品（洛赛克、奥克、奥美拉唑）４０ｍｇ在健康人的生物利用度及对胃内２４ＰＨ值的影响。方法 交叉试验设计：１８例健康志原者（男１２例,女６例）被随机分成３组,每组交叉服用洛塞克、奥克、奥美拉唑胶囊１次４０ｍｇ,交叉间隔时间７天。结果 药代动力学研究结果表明相对于奥克胶囊与奥美拉唑胶囊,洛赛克胶囊有吸收速度快、血药浓度高与持续时间长及生物利用度高的优点。胃内２４Ｐ俞 不同胶囊服用     

Effect of a proton pump inhibitor AG-1749 (lansoprazole) on intragastric pH: 24-hour intragastric pH monitoring]

Proton pump inhibitors, as agents for use against peptic ulcers, potently suppress gastric acid secretion, as is the case with H2 receptor antagonists. To evaluate this antisecretory action as objectively as possible, intragastric pH was continuously monitored during 24 hours. Eight subjects were enrolled and divided into 2 treatment groups: a group receiving a daily dose of 30 mg of AG-1749 (lansoprazole) and the other group receiving 60 mg. Intragastric pH recording was made in each subject before and after the consecutive administration of the drug, and the corresponding pH holding time was calculated to evaluate the effect obtained in each group. The result indicated that the proportion of time in 24 hours after medication during which the pH was maintained above each level was significantly larger than that after placebo administration, and the duration of action was superior to that of H2-receptor antagonists. From the above, it was concluded that the consecutive administration of ag-1749, at doses of 60 mg as well as 30 mg, exhibits excellent antisecretory action in terms of intragastric pH control.     

The effect of the H2-antagonist niperotidine on intragastric acidity in healthy subjects undergoing 24-hour pH-monitoring

The effects of niperotidine, a novel histamine H2-receptor antagonist, on nocturnal gastric acid secretion in healthy volunteers, have been investigated. Twenty subjects were randomly assigned to the placebo (M:F = 7:3; Age 34 +/- SD3 yrs) or to the niperotidine-treated group (M:F = 7:3; Age: 37 +/- 6 yrs) in which 460 mg were administered at 22.00. Intragastric acidity was assessed by means of 24-hour pH-measurement (10.00-22.00) using sensitive antimony monocrystalline electrodes. The percentage of daytime gastric acidity (prandial and interprandial) was similar in both groups (median; interquartile range): placebo group 87.5; 69.5-90.1 vs niperotidine 85.8; 59-89.1. Niperotidine increased the intragastric pH during the period 22.00-10.00. The percentage of time above pH 4 was higher in the treated group (28.4; 14.8-50.7% vs 7.4; 1.4-10.7%; p less than 0.02). The duration of niperotidine action was 5 to 7 hours. The nocturnal pH frequency curve after niperotidine was shifted toward alkaline values with a decrease of acidity in the pH range 1-2 (p less than 0.04). We conclude that a bedtime dose of niperotidine inhibits nocturnal gastric acid secretion in healthy subjects.     

埃索美拉唑对健康志愿者抑制胃泌酸的药效学研究

目的　比较埃索美拉唑与雷贝拉唑对健康志愿者抑制胃泌酸的效果及安全性。方法　 36名健康志愿者随机分为两组 ,分别口服埃索美拉唑 4 0mg或雷贝拉唑 10mg ,每日 1次 ,连续 5d ,经过14d的洗脱期后 ,交叉口服雷贝拉唑 10mg或埃索美拉唑 4 0mg ,每日 1次 ,连续 5d。分别于服药首日及第 5天连续测定 2 4h胃内 pH ,并以PCR方法鉴定细胞色素 (CYP) 2C19基因型。 结果　埃索美拉唑组服药后首日最初 4、2 4h和第 5天 2 4h胃内pH >4 .0的时间百分比分别为 5 8.9%、73.7%和 84 .2 % ,显著高于雷贝拉唑组 (32 .1%、5 4 .8%和 76 .2 % ,P <0 .0 0 1) ;胃内 pH中位值分别为 4 .2 9、5 .6 0和 6 .38,亦显著高于雷贝拉唑组 (2 .88、4 .2 6和 5 .77,P≤ 0 .0 0 1)。服药后首日及第 5天pH >4 .0超过 16h的志愿者埃索美拉唑组百分率分别为 6 3.9%和 88.9% ,亦显著高于雷贝拉唑 (33.3%和 6 1.1% ,P <0 .0 5 )。36名志愿者中 2 8名CYP 2C19基因型为强代谢型 ,8名为弱代谢型。两药对强代谢型或弱代谢型者胃泌酸的抑制差异无显著性 (P >0 .0 5 )。服药期间两组均未发生明显不良反应。结论　埃索美拉唑和雷贝拉唑均具有较强的抑制胃酸分泌效应 ,但在抑酸速度、抑酸强度和维持时间方面 ,4 0mg埃索美拉唑优于 10mg雷贝拉唑。两药