BACKGROUND & AIMS: :Few reports exist on allergic reactions to ranitidine. We present a case of bronchospastic reaction to ranitidine occurred during a drug challenge test. After administration of a therapeutic dose of ranitidine, the patient showed dyspnea, cough and bronchospasm in all the lung fields. Personal respiratory background was negative for respiratory disease and asthma. On reviewing the literature we found no reports of bronchospastic reaction to ranitidine. Quickness and the clinical characteristics of the adverse reaction suggest a pathogenic mechanism of immediate-type hypersensitivity.

背景与目标： : 关于雷尼替丁过敏反应的报道很少。我们介绍了在药物激发试验期间发生的对雷尼替丁的支气管痉挛反应的情况。给予治疗剂量的雷尼替丁后，患者在所有肺野均表现出呼吸困难，咳嗽和支气管痉挛。个人呼吸背景对呼吸系统疾病和哮喘阴性。在回顾文献时，我们没有发现雷尼替丁发生支气管痉挛反应的报道。快速反应和不良反应的临床特征提示了即刻型超敏反应的致病机制。

BACKGROUND & AIMS: :Ranitidine bismuth citrate (Pylorid, Tritec) is a novel drug which heals peptic ulcers and when co-prescribed with either clarithromycin or amoxycillin eradicatesHelicobacter pylori. In controlled clinical studies it was well-tolerated when given alone or when co-prescribed with either antibiotic. Data from 20 clinical studies are reported in this analysis of safety with almost 5000 patients having received ranitidine bismuth citrate (200, 400, or 800 mg twice daily). The incidence of adverse events reported with this new drug, either alone or with an antibiotic, was not different from or lower than in patients given placebo and was independent of the dose of ranitidine bismuth citrate tested. Most commonly reported events (>1% of patients) were upper respiratory tract infection, constipation, diarrhoea, nausea and vomiting, dizziness, and headache, the latter being the only event reported by >2% of patients who received ranitidine bismuth citrate alone. Adverse events considered by the clinical investigator to be adverse reactions occurred with a similar frequency amongst patients given ranitidine bismuth citrate (8%), ranitidine hydrochloride (6%), or placebo (6%). The incidence of adverse reactions was greater when co-prescribed with amoxycillin (11%) or clarithromycin (20%) although it was not different from that noted with the antibiotics alone. Serious adverse events were reported in similar proportions of patients given placebo, ranitidine bismuth citrate alone or with an antibiotic, and ranitidine hydrochloride (range: <1-2%). The safety profile of ranitidine bismuth citrate was thus comparable to that of ranitidine hydrochloride (Zantac), a drug with a well-established record of safety in clinical use.

背景与目标： : 雷尼替丁柠檬酸铋 (Pylorid，Tritec) 是一种治疗消化性溃疡的新药，与克拉霉素或阿莫西林共同开处方时可根除幽门螺杆菌。在对照临床研究中，单独给药或与任何一种抗生素共同开处方时，耐受性良好。在该安全性分析中报告了来自20项临床研究的数据，其中几乎5000名接受雷尼替丁柠檬酸铋 (200，400或800 mg，每天两次) 的患者。使用这种新药 (单独使用或使用抗生素) 报告的不良事件发生率与服用安慰剂的患者没有差异或低于服用安慰剂的患者，并且与雷尼替丁柠檬酸铋的剂量无关。最常见的事件 (>1% 的患者) 是上呼吸道感染，便秘，腹泻，恶心和呕吐，头晕和头痛，后者是仅接受雷尼替丁柠檬酸铋的患者中> 2% 报告的唯一事件。在接受雷尼替丁 (8%)，盐酸雷尼替丁 (6%) 或安慰剂 (6%) 的患者中，临床研究者认为是不良反应的不良事件以相似的频率发生。与阿莫西林 (11%) 或克拉霉素 (20%) 共同处方时，不良反应的发生率更高，尽管与单独使用抗生素时没有什么不同。在给予安慰剂、雷尼替丁单独或与抗生素和盐酸雷尼替丁的患者中，报告了类似比例的严重不良事件 (范围: <1-2%)。因此，雷尼替丁柠檬酸铋的安全性与盐酸雷尼替丁 (Zantac) 相当，后者是一种在临床使用中具有良好安全性记录的药物。

BACKGROUND & AIMS: OBJECTIVE:To determine whether the H2-receptor antagonist, ranitidine, which is a potent inhibitor of gastric alcohol dehydrogenase activity in vitro, increases the bioavailability of orally administered ethanol (0.3 g/kg of body weight) and to compare the resulting blood alcohol concentrations with those of two other H2-antagonists, cimetidine and famotidine, the latter of which does not inhibit gastric alcohol dehydrogenase. DESIGN:For each of the H2-receptor antagonists, a different group of subjects was used. In each group, a paired design was adopted with each subject serving as his own control. SETTING:Hospital laboratory. SUBJECTS:Normal, healthy men aged 24 to 46 years. INTERVENTION:Eight men were treated for 1 week with ranitidine (300 mg/d), six with cimetidine (1000 mg/d), and six with famotidine (40 mg/d). MEASURES:Peak blood alcohol concentrations, areas under the blood alcohol curve, first-pass metabolism, and bioavailability of orally consumed ethanol. RESULTS:Relative to baseline, ranitidine increased the mean peak concentration and the area under the curve of blood alcohol concentrations by 34% (P less than .05) and 41% (P less than .01), respectively. First-pass metabolism of ethanol was decreased from 70 +/- 10 to 31 +/- 9 mg/kg of body weight, with a corresponding increase in ethanol bioavailability of 79.6% to 92.6%. By comparison, cimetidine had even a greater effect on blood alcohol levels, while famotidine had no significant effects. CONCLUSION:Patients treated with ranitidine or cimetidine should be warned of possible functional impairments after consumption of amounts of ethanol considered safe in the absence of such therapy.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:The purpose of this study was to investigate if the use of a higher night time dose of ranitidine (300 mg) could keep significantly more duodenal ulcer patients in remission than the usual maintenance dose (150 mg).

METHODS:Double-blind, multi-centre, parallel group study of patients with proven healed duodenal ulcer randomized to ranitidine 150 mg or 300 mg daily for 1 year. The primary study end-point was symptomatic, endoscopically proven ulcer relapse.

RESULTS:A total of 489 patients were recruited into the study. The endoscopically proven relapse rates were 6.1% of ranitidine 150 mg daily (n = 250) and 6.9% on 300 mg daily (n = 239). These differences were not statistically significant.

CONCLUSION:This study provides further evidence that maintenance therapy with ranitidine 150 mg daily is highly effective at preventing duodenal ulcer relapse. The use of the higher dose of 300 mg daily does not appear to keep significantly more patients in remission.

背景与目标： 背景 : 这项研究的目的是调查是否使用较高的夜间剂量的雷尼替丁 (300 mg) 可以使十二指肠溃疡患者的缓解比通常的维持剂量 (150 mg) 明显更多。
方法 : 双盲，多中心，平行组研究，已证实已治愈的十二指肠溃疡患者随机分配给雷尼替丁150 mg或300 mg，每天1年。主要研究终点是有症状的，经内镜证实的溃疡复发。
结果 : 总共招募了489名患者。经内镜证实的复发率是雷尼替丁每天150 mg (n = 250) 和6.9% 每天300 mg (n = 239) 6.1%。这些差异在统计学上并不显着。
结论 : 这项研究提供了进一步的证据，表明每天使用雷尼替丁150 mg维持治疗可有效预防十二指肠溃疡复发。每天使用较高剂量的300 mg似乎并不能使更多的患者缓解。

BACKGROUND & AIMS: The effects of a ranitidine-zinc complex and ranitidine alone were compared in three different experimental models (pyloric ligation, ethanol and indomethacin) of gastric ulceration in the rat. In the pyloric ligation model, the ranitidine-zinc complex (50, 100 and 150 mg/kg p.o.) showed antiulcerogenic activity similar to that observed with equimolar doses of ranitidine (35, 70 and 105 mg/kg p.o.). Both the ranitidine-zinc complex and ranitidine significantly reduced (p < 0.05) gastric acid secretion in a dose-dependent manner. The protective effect of the ranitidine-zinc complex (100 and 150 mg/kg p.o.) against gastric damage developing after p.o. administration of absolute ethanol or indomethacin was enhanced (p < 0.05) with respect to that obtained with equimolar doses of ranitidine (70 and 105 mg/kg p.o.). The presence of zinc in the ranitidine-zinc complex does not interfere with the antisecretory effects of ranitidine on the gastric mucosa, while it confers an additional cytoprotective action to the final compound.

背景与目标： 在大鼠胃溃疡的三种不同实验模型 (幽门结扎，乙醇和吲哚美辛) 中比较了雷尼替丁-锌复合物和单独雷尼替丁的作用。在幽门结扎模型中，雷尼替丁-锌复合物 (50、100和150 mg/kg p.o.) 表现出与等摩尔剂量雷尼替丁 (35、70和105 mg/kg p.o.) 相似的抗溃疡活性。雷尼替丁-锌复合物和雷尼替丁均以剂量依赖性方式显著减少 (p < 0.05) 胃酸分泌。雷尼替丁-锌复合物 (100和150 mg/kg p.o.) 对p.o.后发生的胃损伤的保护作用。相对于等摩尔剂量的雷尼替丁 (70和105 mg/kg p.o.) 获得的无水乙醇或消炎痛的给药增强 (p <0.05)。雷尼替丁-锌复合物中锌的存在不会干扰雷尼替丁对胃粘膜的抗分泌作用，同时赋予最终化合物额外的细胞保护作用。

BACKGROUND & AIMS: BACKGROUND:The aim of this study was to determine the effect of gestational age on pharmacokinetics of ranitidine in newborns with gastroesophageal reflux. METHODS:A prospective, descriptive and pharmacokinetic study was carried out in 30 pre-term and 20 full-term babies. 3 mg/kg of ranitidine was administered intravenously to all the babies and at 0.25, 0.5, 1, 2, 4, and 8 h following the administration, samples of blood were drawn to assess ranitidine levels using high performance liquid chromatographic technique. RESULTS:Pharmacokinetics of ranitidine had a bi-exponential behavior with a half-life elimination of (t1/2el) 2.79 h, area under curve (AUC) of 1688 ng/mL, volume of distribution (Vd) of 1.44 L/kg, and clearance (Cl) of 5.9 L/kg/h. The median plasmatic concentration in pre-terms was 1113 ng/mL and 280 ng/mL in full-terms. Vd, t1/2 and Cl presented high values in preterm although the correlation of Cl with glomerular filtration in term newborns was better. CONCLUSIONS:Plasma levels of ranitidine depend on the gestational age of the newborns. However, the possible relationship between after-birth age and pharmacokinetics of the neonates as their internal organs get matured without minding their gestational background.

背景与目标：

BACKGROUND & AIMS: Although rare, bradycardia and other cardiac arrhythmias have been associated with the use of H2-receptor antagonists. Ranitidine is among the most frequently prescribed drugs. In this article, the authors observed a ranitidine-mediated sinus bradycardia in a man with dextrocardia (situs inversus) who had acute bleeding from a duodenal ulcer. The bradycardia was resolved after ranitidine was discontinued.

背景与目标： 尽管罕见，但心动过缓和其他心律失常与使用H2-receptor拮抗剂有关。雷尼替丁是最常用的处方药之一。在本文中，作者观察到雷尼替丁介导的右位心 (situs inversus) 男性十二指肠溃疡急性出血的窦性心动过缓。停用雷尼替丁后心动过缓。

BACKGROUND & AIMS: Morphine and tubocurarine may release histamine by direct mast cell degranulation which may result in systemic effects such as cutaneous flushing, local wheal and flare formation and hypotension. This randomised, double-blind study examined whether preoperative combined oral terfenadine (60 mg) and ranitidine (150 mg) attenuates the reduction in blood pressure and cutaneous flushing after the administration of tubocurarine and morphine in 60 patients undergoing elective gynaecological surgery. In addition, investigation was made of whether tubocurarine and morphine cause a significant decrease in gastric pH in comparison to the nonhistamine-releasing agents fentanyl and vecuronium. Patients were randomly assigned to one of three groups receiving either pre-operative terfenadine and ranitidine and intra-operative tubocurarine and morphine (group A); pre-operative placebo and intra-operative tubocurarine and morphine (group B); pre-operative placebo and intra-operative fentanyl and vecuronium (group C). Compared to group B, group A had less hypotension and tachycardia but no significant decrease in cutaneous flushing immediately following morphine and tubocurarine (p > 0.05). There were no significant differences in haemodynamic changes between the groups A and C. In those patients not pretreated with terfenadine and ranitidine (groups B and C), gastric pH decreased between 5 and 10 min following bolus administration of morphine and tubocurarine (group B), whereas patients receiving fentanyl and vecuronium (group C) had an increase in gastric pH. This suggests that histamine release following administration of morphine and tubocurarine is sufficient to increase gastric acidity.(ABSTRACT TRUNCATED AT 250 WORDS)

背景与目标： 吗啡和tubocurarine可通过直接肥大细胞脱颗粒释放组胺，这可能导致全身作用，例如皮肤潮红，局部风团和耀斑形成和低血压。这项随机，双盲研究检查了60例接受择期妇科手术的患者，术前联合口服特非那定 (60 mg) 和雷尼替丁 (150 mg) 是否减轻了给予tubocurarine和吗啡后血压和皮肤潮红的降低。此外，与非组胺释放剂芬太尼和维库溴铵相比，进行了研究，是否与吗啡和吗啡引起胃pH显着降低。患者被随机分配到三组之一，分别接受术前特非那定和雷尼替丁以及术中tubocurarine和吗啡 (A组); 术前安慰剂和术中tubocurarine和吗啡 (B组); 术前安慰剂和术中芬太尼和维库溴铵 (C组)。与B组相比，A组的低血压和心动过速较少，但吗啡和小管碱后即刻皮肤潮红无明显减少 (p> 0.05)。A组和C组之间的血液动力学变化没有显着差异。在未接受特非那定和雷尼替丁预处理的患者 (B和C组) 中，在推注吗啡和tubocurarine后5至10分钟内胃ph值降低 (B组)，而接受芬太尼和维库溴铵的患者 (C组) 胃ph值升高。这表明吗啡和tubocurarine给药后的组胺释放足以增加胃酸度。(摘要截短于250字)

BACKGROUND & AIMS: :The effects of oral omeprazole and oral ranitidine on gastric fluid volume and pH were compared in 95 elective surgical patients, randomly assigned to one of three groups. The patients received either 80 mg of omeprazole or 300 mg of ranitidine orally at 6.00 on the morning of surgery. One third of the patients received no antacid therapy. Following induction, a no. 18 nasogastric tube was passed into the stomach and all available gastric fluid was aspirated. pH and volumes were measured. In the omeprazole- and ranitidine-treated groups, the mean pH was > 5.4 after induction, at completion of surgery and 1 h after operation, although at least one patient in both groups had pH < 2.5. The volumes of gastric aspirates were reduced equally by both drugs. Two patients in the omeprazole group, none in the ranitidine group and eight in the control group (26%) had pH < 2.5 with volume > 25 ml at induction. Both drugs appeared to be effective in reducing the volume of intragastric fluid and acidity to acceptable values.

背景与目标： : 比较了95例择期手术患者口服奥美拉唑和口服雷尼替丁对胃液量和pH的影响，随机分为三组之一。患者在手术的早晨6.00时口服80 mg奥美拉唑或300 mg雷尼替丁。三分之一的患者没有接受抗酸治疗。诱导后，将18号鼻胃管送入胃中，并抽吸所有可用的胃液。测量ph值和体积。在奥美拉唑和雷尼替丁治疗组中，诱导后、手术完成时以及手术后1小时的平均pH> 5.4，尽管两组中至少有一名患者的pH <2.5。两种药物均减少了胃抽吸物的体积。奥美拉唑组2例，雷尼替丁组无一例，对照组8例 (26%) 诱导时pH <2.5，体积> 25毫升。两种药物似乎都可以有效地将胃内液的体积和酸度降低到可接受的值。

BACKGROUND & AIMS: A double-blind multinational comparison of ranitidine 300 mg post evening meal (pem), ranitidine 300 mg nocte and cimetidine 800 mg nocte has been carried out in 1677 patients with endoscopically verified duodenal ulcer disease. Fifty-three percent of ulers healed by two weeks during treatment with ranitidine 300 mg pem and 88% by four weeks, while the results for ranitidine 300 mg nocte were 50% and 86%, respectively, and 44% and 84% for cimetidine. The difference between ranitidine 300 mg pem and cimetidine was significant at two weeks (P = 0.002, Mantel-Haenszel chi-squared test). The relative efficacy of the treatments was not dependent upon gender, smoking habit, alcohol intake, or ulcer frequency. However, the overall differences in healing between patients with small and large ulcers and patients with single and multiple ulcers were significantly different at weeks 2 and 4 (P < 0.001). Significantly more patients treated with ranitidine (60%) had complete relief of epigastric pain than those treated with cimetidine (54%) (P < 0.05). A meta-analysis of the four double-blind comparisons of ranitidine 300 mg pem (N = 841) and 300 mg nocte (N = 849), including the present study, failed to show the benefits of pem dosing, predicted from pharmacological studies.

背景与目标： 对1677例经内镜证实的十二指肠溃疡病患者进行了雷尼替丁300 mg晚餐后 (pem)，雷尼替丁300 mg nocte和西咪替丁800 mg nocte的双盲跨国比较。在用雷尼替丁300 mg pem治疗期间，50 3% 的ulers在两周内愈合，并在四周内88%，而雷尼替丁300 mg nocte的结果分别为50% 和86%，西咪替丁的结果为44% 和84%。雷尼替丁300 mg pem和西咪替丁在两周时差异显著 (P = 0.002，Mantel-Haenszel卡方检验)。治疗的相对疗效不取决于性别，吸烟习惯，饮酒或溃疡频率。然而，在第2周和第4周，小溃疡和大溃疡患者与单个溃疡和多溃疡患者之间的愈合总体差异显着 (P <0.001)。与西咪替丁 (54%) 治疗的患者相比，雷尼替丁 (60%) 治疗的患者完全缓解了上腹痛 (P <0.05)。雷尼替丁300 mg pem (N = 841) 和300 mg nocte (N = 849) 的四项双盲比较的荟萃分析 (包括本研究) 未能显示出药理学研究预测的pem给药的益处。

BACKGROUND & AIMS: Both ranitidine and metoclopramide produce neuropsychiatric side effects. Concomitant use of these drugs preoperatively may produce adverse behavioral and emotional changes. Therefore, in 123 unpremedicated patients undergoing tubal occlusion, behavior, cognitive function, and affect were studied before and after a 2-min intravenous injection of placebo (n = 30), ranitidine 50 mg (n = 32), metoclopramide 10 mg (n = 30), or both ranitidine 50 mg and metoclopramide 10 mg (n = 31). Cognitive function was evaluated by the responses to 11 statements devised to assess attitude toward anesthesia and surgery. Affect was assessed by the word chosen out of 11 word-pairs as best describing the feelings at the time. After ranitidine injection, one patient seemed restless and five seemed drowsy. The changes were associated with subjective feelings of agitation (P < 0.05) and restlessness (P < 0.05). After metoclopramide injection, 6 (20%) developed akathisia, 13 (43.3%) seemed restless, and 8 (26.7%) seemed drowsy. The changes were associated with subjective sensation of jumpiness (P < 0.01) and discomfort (P < 0.05). When both ranitidine and metoclopramide were injected, 10 (32.3%) developed akathisia, 4 (12.4%) seemed restless, and 11 (35.5%) seemed drowsy. The changes were associated with subjective feelings of agitation (P < 0.05), jumpiness (P < 0.05), restlessness (P < 0.01), and upset (P < 0.05). Akathisia, a side effect of metoclopramide, seemed to be more prominent when ranitidine was added.

背景与目标： 雷尼替丁和甲托普胺都产生神经精神副作用。术前同时使用这些药物可能会产生不良的行为和情绪变化。因此，在123例未接受输卵管阻塞的患者中，在静脉注射2分钟安慰剂 (n = 30)，雷尼替丁50 mg (n = 32)，甲托普胺10 mg (n = 30) 之前和之后研究了行为，认知功能和情感。或雷尼替丁50 mg和甲托普胺10 mg (n = 31)。通过对11条旨在评估对麻醉和手术态度的陈述的反应来评估认知功能。情感是通过从11个单词对中选择的单词来评估的，该单词最能描述当时的感受。雷尼替丁注射后，一名患者似乎焦躁不安，五名患者似乎昏昏欲睡。这些变化与主观躁动 (P < 0.05) 和躁动 (P < 0.05) 有关。注射甲托普胺后，6 (20%) 出现静坐不能，13 (43.3%) 似乎不安，8 (26.7%) 似乎昏昏欲睡。这些变化与主观感觉跳跃 (P < 0.01) 和不适 (P < 0.05) 有关。同时注射雷尼替丁和甲托普胺时，10 (32.3%) 出现静坐不能，4 (12.4%) 似乎不安，11 (35.5%) 似乎昏昏欲睡。这些变化与主观躁动感 (P <0.05)，跳跃感 (P <0.05)，躁动感 (P < 0.01) 和心烦感 (P < 0.05) 有关。静坐不能，甲托普胺的副作用，在添加雷尼替丁时似乎更突出。

BACKGROUND & AIMS: BACKGROUND:Immunoglobulin E (IgE) is important in allergic reactions and in host defense against parasites. IgE may also participate in the acute-phase response to physical stress. This study aimed to determine whether major abdominal surgery induced increased serum IgE levels, and whether treatment with ranitidine or prednisolone influenced the IgE response to surgery. METHODS:For assessment of the IgE response to surgery and the effect of ranitidine, 24 patients scheduled for major abdominal surgery were randomized to receive either perioperative treatment with ranitidine or no treatment. To evaluate the effect of glucocorticoids, 24 patients undergoing major elective abdominal surgery were randomized to receive preoperative treatment with either prednisolone or placebo. IgE levels were determined in serum samples drawn pre- and postoperatively. RESULTS:In the ranitidine study, both the control group and the ranitidine-treated group displayed a postoperative increase (P<0.001) of serum IgE. In the prednisolone study, a postoperative increase (P<0.05) of serum IgE was detected in the placebo group. No significant increase was found in the prednisolone-treated group. CONCLUSIONS:Major abdominal surgery induces an increase of serum IgE. This increase can be prevented by preoperative treatment with prednisolone, but not with ranitidine.

背景与目标：

BACKGROUND & AIMS: :Males and females respond differently to drugs: indeed, sex plays a crucial role in determining drug pharmacokinetics and pharmacodynamics. Excipients have also been shown to enhance the biovailability of drugs differently in men and women. The aim of this work was to investigate whether rodents are a good model in which to study sex-specific effects of polyethylene glycol 400 (PEG 400) on the bioavailability of ranitidine. Ranitidine (50mg/kg) was dissolved in water with different amounts of PEG 400-0 (control), 13, 26, 51, 77, 103, and 154mg/kg; these solutions were dosed orally by gavage to male and female Wistar rats. Blood samples were withdrawn over 480min and assayed via HPLC-UV. Individual ranitidine plasma profiles were constructed for each rat, and standard pharmacokinetic parameters were determined. In the male rats, the change in the area under the plasma ranitidine curve (AUC0-480) compared to the control group, was +18%; +49% (p<0.05); +37% (p<0.05); +31% (p<0.05); +8% and -22% (p<0.05) for PEG 400 doses of 13; 26; 51; 77; 103; and 154mg/kg respectively. On the other hand, females showed no statistically significant difference between the groups. In conclusion, low doses of PEG 400 enhanced the bioavailability of ranitidine in male, but not female, rats. These findings are in agreement with previously published human data, therefore confirming the validity of the rodent model, and highlight the unusual and clinically significant phenomenon that an excipient can influence drug bioavailability in one gender and not the other.

背景与目标： : 男性和女性对药物的反应不同: 事实上，性别在决定药物药代动力学和药效学中起着至关重要的作用。赋形剂也已被证明可以不同地增强男性和女性药物的生物可吸收性。这项工作的目的是研究啮齿动物是否是研究聚乙二醇400 (PEG 400) 对雷尼替丁生物利用度的性别特异性影响的良好模型。将雷尼替丁 (50 mg/kg) 溶解在具有不同量的PEG 400-0 (对照)，13、26、51、77、103和154 mg/kg的水中; 这些溶液通过管饲法口服给雄性和雌性Wistar大鼠。在480分钟内取出血液样品，并通过hplc-uv测定。为每只大鼠构建了雷尼替丁的血浆图谱，并确定了标准的药代动力学参数。在雄性大鼠中，与对照组相比，雷尼替丁曲线下面积 (AUC0-480) 的变化为18%; 49% (p<0.05); 37% (p<0.05); 31% (p<0.05); 8% 和-22% (p<0.05)，PEG 400剂量分别为13; 26; 51; 77; 103; 和154 mg/kg。另一方面，女性在两组之间没有统计学上的显着差异。总之，低剂量的PEG 400增强了雷尼替丁在雄性但非雌性大鼠中的生物利用度。这些发现与先前发表的人类数据一致，因此证实了啮齿动物模型的有效性，并强调了赋形剂可以影响一种性别而不是另一种性别的药物生物利用度的不寻常且具有临床意义的现象。

BACKGROUND & AIMS: INTRODUCTION:In September 2019, ranitidine and nizatidine were suggested to contain N-nitrosodimethylamine, a carcinogenic substance. People have since been concerned about the potential impact of ranitidine/nizatidine use on the risk of cancer. OBJECTIVE:The objective of this study was to investigate the risk of cancer among people receiving ranitidine or nizatidine compared with other histamine 2 receptor antagonists (H2 blockers) [cimetidine, famotidine, roxatidine, and lafutidine]. METHODS:In the Japan Medical Data Center claims database (comprising people aged < 75 years) from 2005 to 2018, we identified new adult users of H2 blockers and classified them into ranitidine/nizatidine users and other H2 blocker users. We estimated the incidence of cancer diagnosis in each group and conducted a multivariable Cox regression analysis. RESULTS:We identified 113,745 new users of ranitidine/nizatidine (median age 41.2 years [interquartile range 31.7-51.1]; 49.1% men; median follow-up 2.4 years [1.1-4.5]) and 503,982 new users of other H2 blockers (median age 40.9 years [31.1-51.2]; 51.0% men; median follow-up 2.3 years [0.9-4.2]). The incidence rate of cancer diagnosis was 6.39 (95% confidence interval 6.13-6.66) cases per 1000 person-years (top three sites: breast 14.8%; colorectal 14.6%; and stomach 11.5%) in the ranitidine/nizatidine group and 6.17 (6.05-6.30) cases per 1000 person-years (colorectal 14.7%; breast 13.5%; and stomach 11.2%) in the other H2 blockers group. The adjusted hazard ratio (ranitidine/nizatidine users vs other H2 blocker users) was 1.02 (0.98-1.07). The results were similar by follow-up length, by cancer site, and when ranitidine and nizatidine users were separately compared with the other H2 blockers group. By cumulative dose, the adjusted hazard ratio (95% confidence interval) was 1.03 (0.98-1.08) from 1 to 180 defined daily doses (DDDs), 1.00 (0.73-1.39) from 181 to 365 DDDs, 0.95 (0.61-1.48) from 366 to 730 DDDs, and 0.83 (0.45-1.55) at > 730 DDDs. CONCLUSIONS:We found no evidence that ranitidine/nizatidine is associated with an increased risk of cancer, although further studies with more accurate measurement of exposure, inclusion of older people, and longer follow-up may be needed.

背景与目标：

BACKGROUND & AIMS: Pantoprazole is a new substituted benzimidazole, which is a potent inhibitor of gastric acid secretion by its inhibition of H+,K(+)-ATPase. Pantoprazole, 40 mg, was compared with the H2-receptor antagonist ranitidine, 300 mg, in the healing of acute duodenal ulcer. Two hundred seventy-six patients with endoscopically diagnosed duodenal ulcer were studied in this multicenter double-blind study. Patients were reendoscopied after two weeks of treatment, and those patients whose ulcers remained unhealed were also endoscoped after an additional two weeks of treatment. The primary end point was the complete healing of the ulcer. Demographic characteristics were comparable in both treatment groups. After two weeks of treatment, 90/124 (73%) patients in the pantoprazole group had healed ulcers compared with 57/126 (45%) patients in the ranitidine group (P < 0.001, per-protocol analysis). After four weeks, the cumulative healing rates were 92% and 84% in the pantoprazole and ranitidine groups, respectively (P = 0.073). Symptoms were also improved at week 2, with 84% and 72% of patients in the pantoprazole and ranitidine groups, respectively, reporting no ulcer pain (P < 0.05, per-protocol analysis). Both treatments were well tolerated. This study has confirmed the superiority of pantoprazole compared with ranitidine in the healing of duodenal ulcers and pain relief after two weeks of treatment and has shown pantoprazole to be well tolerated in this indication.

背景与目标： 泮托拉唑是一种新的取代苯并咪唑，它通过抑制H，K ()-atp酶而成为胃酸分泌的有效抑制剂。将40 mg的泮托拉唑与H2-receptor拮抗剂雷尼替丁300 mg在急性十二指肠溃疡的愈合中进行了比较。在这项多中心双盲研究中，对76例经内镜诊断为十二指肠溃疡的患者进行了研究。治疗两周后，患者进行了内窥镜检查，而那些溃疡仍未愈合的患者在另外两周的治疗后也进行了内窥镜检查。主要终点是溃疡完全愈合。两个治疗组的人口统计学特征具有可比性。治疗2周后，泮托拉唑组90/124例 (73% 例) 溃疡愈合，雷尼替丁组57/126例 (45% 例) 溃疡愈合 (P <0.001，符合方案分析)。4周后，泮托拉唑组和雷尼替丁组的累积治愈率分别为92% 和84% (P = 0.073)。在第2周时症状也得到改善，泮托拉唑组和雷尼替丁组分别有84% 和72% 患者，报告无溃疡疼痛 (P <0.05，符合方案分析)。两种治疗都具有良好的耐受性。这项研究证实了泮托拉唑与雷尼替丁相比，在治疗两周后的十二指肠溃疡愈合和缓解疼痛方面具有优势，并表明泮托拉唑在这种适应症中具有良好的耐受性。