High quality of ulcer healing in rats by lafutidine, a new-type histamine H2-receptor antagonist: involvement of capsaicin-sensitive sensory neurons

This study was conducted to determine whether the low recurrence rate of ulcers after treatment with lafutidine, an antiulcer drug possessing both an antisecretory and gastroprotective activities, was mediated by capsaicin-sensitive sensory neurons (CSSN). Chronic gastric ulcers in rats were induced by serosa-searing. The ulcer healing and recurrence were evaluated by endoscopy. Drugs were orally administered. Desensitization of CSSN was induced by pretreatment with capsaicin. Lafutidine (30 mg/kg) accelerated the ulcer healing significantly, and the recurrence rate was much lower than that for the vehicular control. In CSSN-desensitized rats, lafutidine also accelerated the ulcer healing significantly, but the low recurrence rate shown in normal rats was counteracted. The recurrence rate of the combination of famotidine (30 mg/kg) and teprenone (100 mg/kg) was lower than that of famotidine alone. In conclusion, the low recurrence rate of ulcers after lafutidine treatment in rats seems to depend on the gastroprotective mechanisms involving CSSN.     

瑞巴派特联合法莫替丁治疗活动期胃溃疡61例

目的评估瑞巴派特联合法莫替丁治疗幽门螺杆菌感染的活动期胃溃疡患者溃疡愈合质量。方法采用多中心、随机、开放、阳性药物对照研究设计。120例患者随机分为治疗组与对照组。治疗组用瑞巴派特100 mg,po,tid,法莫替丁片20mg,po,bid;对照组用奥美拉唑胶囊20 mg,每日晨空腹口服。疗程均为6 wk。治疗前后分别行病理组织学检查评估溃疡愈合质量。结果治疗6 wk后,2组患者上腹痛、腹胀、反酸、嗳气等症状均有显著改善(P<0.01)。2组溃疡愈合有效率无显著性差异。2组患者治疗后组织学表现较治疗前显著好转(P<0.01)。治疗组患者中性黏液含量恢复较对照组好(P<0.05)。治疗组发生2例不良反应,对照组无不良反应。治疗组药物费用显著低于对照组,节约治疗费用21.6%。结论瑞巴派特联合法莫替丁治疗伴幽门螺杆菌感染的活动期胃溃疡具有更好的溃疡愈合质量与更少的药物费用。     

Effects of ranitidine on quality of gastric ulcer healing compared with famotidine: a randomized, controlled, multicenter trial

Ranitidine has been found to have anti-inflammatory action as well as antisecretory action in experimental models. However, there are no reports in human gastric ulcer. The aim of this study was to investigate the effects of ranitidine compared with those of famotidine on the quality of gastric ulcer healing. We randomly assigned 69 consecutive patients with gastric ulcers to ranitidine (n = 34) or famotidine (n = 35) for 12 weeks, with endoscopic assessment of the quality of gastric ulcer healing and histological assessment of gastric mucosa 12 weeks after treatment started. Ulcer healing rates of over 95% were very similar in the two groups. The rates of ulcer scars with a flat pattern (good-quality healing) were significantly higher in the ranitidine group than in the famotidine group (per protocol, 63.0% and 34.5%, p = 0.033). The neutrophil infiltration score in the body mucosa treated with famotidine, but not ranitidine, significantly increased after treatment. In contrast, the mononuclear cell infiltration score in the antral mucosa treated with ranitidine, but not in that treated with famotidine, had significantly decreased. In conclusion, initial therapy with ranitidine significantly improved the quality of gastric ulcer healing and the histological scores of gastric mucosa compared with famotidine.     

西沙比利和法莫替丁联用治疗胃溃疡

目的：评估胃肠促动力药西沙比利与法莫替丁联用，对胃溃疡愈合和对上腹部症状的影响。方法：１０６例胃溃疡病人随机分成两组，治疗组口服西沙比利（１０ｍｇ，４次／日）和法莫替丁（２０ｍｇ，２次／日）；对照组仅口服法莫替丁。治疗４周后复查胃镜并评估上腹部症状（包括不适、胀、痛）的缓解。结果：４周后治疗组溃疡愈合率为７７．３６％（４１／５３），对照组溃疡愈合率为５４．７６％（２３／４２），差异有显著性意义（Ｐ     

Antiulcer effect of lafutidine on indomethacin-induced gastric antral ulcers in refed rats.

Lafutidine is a new type antiulcer agent with antisecretory and gastroprotective activities. We investigated the effect of lafutidine on indomethacin-induced antral ulcer in refed rats. Subcutaneous indomethacin injection resulted in the formation of gastric antral ulcer. Lafutidine (1-10 mg/kg, p.o.) reduced the area of ulcer in a dose-dependent manner when administered immediately after the indomethacin injection. Capsaicin at 3 mg/kg, p.o. and 16,16-dimethyl prostaglandin E2 at 3 microg/kg, p.o. also reduced the ulcer area. Chemical deafferentation of capsaicin-sensitive neurons or N(G)-nitro-L-arginine treatment aggravated the ulcer formation and abolished the preventive effect of lafutidine and capsaicin. After the induction of gastric ulcer, lafutidine given twice daily for 2.5 days reduced the area of ulcer in a dose-dependent manner with a significant effect at 10 mg/kg, p.o., as compared with that of the control group. In chemically-deafferentated rats, lafutidine did not show any healing effect. Cimetidine (30 mg/kg, p.o.) and famotidine (1 mg/kg, p.o.) had no significant effect on indomethacin-induced antral ulcer. These results may suggest that lafutidine, unlike cimetidine and famotidine, can prevent the indomethacin-induced antral ulcer formation and accelerate the healing of the ulcer in refed rats through mechanisms involving the capsaicin-sensitive afferent neurons and nitric oxide.     

Effects of pantoprazole on ulcer healing delay associated with NSAID treatment

Nonsteroidal anti-inflammatory drugs delay gastric ulcer healing, and the ability of proton pump inhibitors to counteract this detrimental effect is debated. This study evaluates the effects of pantoprazole on experimental gastric ulcer healing in the presence of indomethacin. Rats with acetic-acid-induced gastric ulcers were orally treated for 3 or 7 days with pantoprazole (15 mumol/kg/day) or famotidine (20 mumol/kg/day), alone or in combination with indomethacin (3 mumol/kg/day). Ulcerated tissues were processed to assess ulcer area, malondialdehyde, proliferating cell nuclear antigen (PCNA) and cleaved caspase-3. Experiments on pylorus-ligated rats indicated that pantoprazole and famotidine were employed at equivalent inhibitory doses on gastric acid secretion (-67.9% and -64.5%, respectively). Indomethacin delayed ulcer healing both at days 3 and 7 (+22 and +35 mm(2) vs control ulcer, respectively). At day 3, pantoprazole was more effective than famotidine in promoting ulcer healing in indomethacin-treated animals (-53.6 and -31.6 mm(2) vs indomethacin, respectively). Malondialdehyde levels and caspase-3 activation in ulcers were increased by indomethacin (+79% and +3.7 folds vs control ulcer, respectively), and these effects were counteracted by pantoprazole (-77.9% and -3.5 folds vs indomethacin, respectively), but not famotidine. Increments of ulcer PCNA expression (+2.5 folds vs normal) were enhanced further by pantoprazole or famotidine, alone or in combination with indomethacin (+8.6 and +10.3 folds vs normal, respectively). Similar results were obtained after 7-day treatments of ulcerated animals with test drugs. It is concluded that, along with acid suppression, pantoprazole exerts acid-independent effects on ulcer healing, which can be ascribed to a decrease in tissue oxidation and apoptosis.     

Omeprazole may be superior to famotidine in the management of iatrogenic ulcer after endoscopic mucosal resection: a prospective randomized controlled trial

BACKGROUND: Acid suppressing agents are widely used to treat the iatrogenic ulcers following endoscopic mucosal resection for gastric neoplasms. However, the relative merits of proton pump inhibitor or histamine(2)-receptor antagonist for endoscopic mucosal resection-induced ulcers are not known. AIM: To prospectively compare omeprazole and famotidine for the healing of endoscopic mucosal resection-induced ulcers and for bleeding control. METHODS: After endoscopic mucosal resection, patients were randomly assigned to omeprazole (20 mg/day) or to famotidine (40 mg/day) group for a 28-day treatment period. The ulcer sizes and stages, bleeding rates and ulcer-related symptoms were compared. RESULTS: A total of 100 patients were randomized equally to each group. Forty-one patients in each group were finally compared. The two groups were comparable in terms of baseline characteristics. Twenty-eight days after treatment, the two groups were not different with respect to ulcer stage (P = 0.137) or ulcer reduction ratio (P = 0.380). No difference was observed with respect to ulcer-related symptoms (P = 0.437) and no bleeding episode occurred in any of the 82 patients. In subgroup that underwent endoscopic submucosal dissection, fewer patients in the omeprazole group showed active ulcers than those in the famotidine group (P = 0.035). CONCLUSION: Our results demonstrate that omeprazole may be superior to famotidine for iatrogenic ulcers following endoscopic mucosal resection, especially for large ulcers.     

Comparison of 40 mg famotidine nightly and 150 mg ranitidine b.d.: ulcer healing and symptom relief in benign gastric ulcer

Two hundred and eight patients with benign gastric ulcers seen on endoscopy were recruited by 13 hospitals in the United Kingdom and Ireland into this double-blind study. Patients were assigned by pre-randomized schedule to 8 weeks of treatment with either 40 mg famotidine at night or 150 mg ranitidine b.d. Repeat endoscopy confirmed complete ulcer healing in 62 of 77 evaluable patients in the famotidine group (81%) and 58 of 71 in the ranitidine group (82%). The treatments were equally effective in promptly relieving day and night pain. Adverse events were uncommon; dizziness and headaches were the most frequently reported in both groups. In conclusion, night-time famotidine is as effective as twice daily ranitidine in healing benign gastric ulcers and provides similarly rapid symptomatic relief.     

Healing-promoting action of rhinax with dual action on chronic gastric and duodenal ulcers induced by acetic acid in rats

Healing promoting actions of Rhinax, a multiconstituent herbal preparation, was investigated in chronic gastric and duodenal ulcer models induced by acetic acid in rats and the effects were compared with those of famotidine by gross of histological evaluation. Rhinax markedly promoted the well balanced healing of gastric ulcer at oral does of 25-100 mg/kg x 2 /day, as evidenced by the reduction of ulcer, regeneration of mucosa and proliferation of connecitve tissue. Rhinax caused an increase in gastric mucosa secretion in all the regenerated mucosa around the gastric ulcers. Famotidine failed to promote the healing of gastric ulcers at 100 mg/kg x 2/ day p.o. Rhinax also significantly accelerated the healing of acetic acid -induced duodenal ulcers as well famotidine. These results indicate that Rhinax is characterised by a potent promoting action on the healing of chronic ulcers, suggesting that the increase in gastric mucus secretion might be associated with the antiulcer action of Rhinax in rats.     

Lansoprazole versus famotidine: efficacy and tolerance in the acute management of duodenal ulceration

Lansoprazole (AG 1749/CG 4801) is an inhibitor of gastric acid secretion by blocking H+,K(+)-ATPase. In this 2:1 randomized, double-blind, multicentre trial lansoprazole 30 mg am was compared to 40 mg famotidine nocte in 264 out-patients suffering from uncomplicated duodenal ulcer. After 2 weeks of treatment ulcer healing was confirmed endoscopically in a significantly higher proportion (P = 0.027) of patients treated with lansoprazole (94/174 = 54.0%) compared to patients receiving famotidine (35/90 = 38.9%). Cumulative healing rates after 4 weeks were 91.4% for the lansoprazole group and 83.3% for the famotidine group (P = 0.065). Pain relief and decrease of concomitant antacid consumption during treatment were comparable in both groups. Both compounds were well tolerated. Rates of recurrent duodenal ulcer in the 6 months after trial treatment were 45/158 (28.5%) after lansoprazole, and 18/69 (26.1%) after famotidine.     

醋氨己酸锌治疗肝硬化合并消化性溃疡

目的 :观察醋氨己酸锌对肝硬化合并消化性溃疡的疗效。方法 :肝硬化合并十二指肠溃疡 36例和合并胃溃疡 30例 ,随机分为醋氨己酸锌组 (醋氨己锌 0 .3g ,po ,tid ,其中胃溃疡 12例、十二指肠溃疡 12例 )、法莫替丁组 (法莫替丁 2 0mg ,po ,bid ,其中胃溃汤 9例、十二指肠溃疡 10例 )、联合用药组 (醋氨己酸锌 0 .3g ,po ,tid ,法莫替丁 2 0mg ,po ,bid ,其中胃溃疡 9例、十二指肠溃疡 14例 ) ,共3组。治疗胃溃疡疗程 6wk ,十二指肠溃疡疗程为4wk ,疗程结束后 ,用内窥镜观察溃疡愈合情况。结果 :醋氨己酸锌组肝硬化合并胃溃疡和十二肠溃疡的愈合率分别为 5 8% ,6 6 % ,法莫替丁组分别为5 6 % ,70 % ,联合用药组分别为 78% ,79% ,3组比较差异无显著意义 ,P >0 .0 5。结论 :醋氨己酸锌治疗肝硬化合并消化性溃疡的疗效与其他 2组相似 ,但其安全性好     

磷酸铝凝胶与法莫替丁治疗消化性溃疡病的疗效对比

目的观察奥美拉唑分别合用磷酸铝凝胶与法莫替丁治疗消化性溃疡的近期愈合率和远期复发率。方法将70例经胃镜检查证实的活动性的消化性溃疡患者随机分为两组,幽门螺杆菌（HP）阳性者先行根除HP三联疗法治疗2周,再续用奥美拉唑20mg口服,每日1次。治疗组加用磷酸铝凝胶,对照组加用法莫替丁,均治疗4周。对溃疡愈合的67例患者进行长程治疗,治疗组（37例）口服磷酸铝凝胶20乳每日2次,对照组（33例）口服莫替丁20mg、睡前1次,均用药0．5年,观察溃疡的累计复发率。结果消化性溃疡的近期愈合率治疗组为94．59％,对照组为90．91％;经胃镜证实,半年累计复发率治疗组为16．67％,对照组为29．03％。结论磷酸铝凝胶短程使用可加速溃疡面的愈合,长程治疗可降低消化性渍疡的复发率,值得临床推广。     

Effect of FRG-8813, a new-type histamine H(2)-receptor antagonist, on the recurrence of gastric ulcer after healing by drug treatment in rats

We investigated the recurrence of ulcers in rats after treatment with FRG-8813, (+/-)-2-(furfurylsulfinyl)-N-[4- [4-(piperidinomethyl)-2-pyridyl] oxy-(Z)-2-butenyl] acetamide, a novel histamine H(2)-receptor antagonist. Chronic gastric ulcers were induced by serosa-searing with a hot metal bar, and the ulcer healing and recurrence after treatment with FRG-8813 or famotidine were evaluated by endoscopy for 160 days. At the dose of 30 mg/kg p. o., once daily, the treatment with FRG-8813 or famotidine for 60 days, which was stopped earlier if the ulcer had healed, accelerated the ulcer healing significantly. A subsequent follow-up study on the healed rats showed that the cumulative recurrence rate of rats healed by FRG-8813 was lower than that of naturally healed rats or rats healed by famotidine. In many cases of rats healed by FRG-8813, the regenerated mucosa was normal in contrast with the control of famotidine-healed animals. The mucosal regeneration index of the gastric ulcer after 10 days' administration of FRG-8813 was significantly higher than that obtained with famotidine. After cessation of the treatment with famotidine for 7 days, rebound hyperacidity was induced; but such rebound did not occur with FRG-8813. Considering the low recurrence rate of ulcers after FRG-8813 treatment, we suggest that FRG-8813 treatment may provide additional benefits in peptic ulcer therapy.     

奥美拉唑、阿莫西林、甲硝唑及法莫替丁对消化性溃疡的疗效观察

目的观察奥美拉唑、阿莫西林、甲硝唑及法莫替丁对消化性溃疡的临床疗效。方法将135例消化性溃疡患者随机分为3组,每组45例:A组用奥美拉唑口服,早晚空腹各1次,20mg/次,阿莫西林口服,1g/次,2次/日,甲硝唑口服,0.4g/次,2次/日,服用1周。之后用法莫替丁口服,早晚空腹各1次,20mg/次,服用3周。B组用奥美拉唑口服,早晚空腹各1次,20mg/次,阿莫西林口服,1g/次,2次/日,甲硝唑口服,0.4g/次,2次/日,服用1周。C组用法莫替丁口服,早晚空腹各1次,20mg/次,服用4周。各组均开始治疗4周后复查胃镜。结果3组消化性溃疡愈合率分别为96%、84%、62%,有显著性差异(P<0.05)。结论消化性溃疡用奥美拉唑、阿莫西林、甲硝唑1周后再以法莫替丁抑制胃酸,疗效更好,治愈率更高。     

Gastric ulcer healing effect of wild honey and its combination with Turmeric（Curcuma domestica Val.） Rhizome on male Wistar rats

Gastric ulcer is a common disorder in human at any ages. In this research, the antiulcer activity of wild honey produced by Apis dorsata, alone or in combination with Turmeric Rhizome, was evaluated in healing acute gastric ulcer. Male Wistar albino rats（150-250 g） were induced ulcers with aspirin at 405 mg/kg BW and ethanol. Antiulcer evaluation was done based on the gastric acidity, numbers and diameter of ulcers, ulcer index, healing ratio, histological examinations, and body weight. The results showed that the groups given honey alone, turmeric alone, and combination of turmeric-honey displayed significant ulcer healing compared to the control group. Ulcers in the group administered with combination of turmeric-wild honey was different significantly from the turmeric alone and wild honey alone groups with increased body weight in that group. The result showed that wild honey（2125 mg/kg BW） had the greatest activity in healing ulcers among other groups. The combination of turmeric-wild honey had a good activity in healing ulcers and increased the body weight of the group.     

Nocturnal therapy with famotidine for 1 year is effective in preventing relapse of gastric ulcer

A multicentre, double-blind, randomized, placebo-controlled trial was undertaken to investigate the therapeutic efficacy of a nocturnal dose of famotidine 20 mg to reduce the 1 year relapse rate of recently healed gastric ulcers. Twenty investigators in eight countries randomized 202 patients with endoscopically confirmed healed gastric ulcers. Repeat endoscopies were performed at 6 and 12 months or for symptoms compatible with ulcer relapse. A per protocol analysis of cumulative life table relapse at 12 months showed that famotidine 20 mg was superior to placebo in reducing gastric ulcer relapse, 24 versus 50%, respectively (P less than 0.01). Both placebo and famotidine were well tolerated. Since nocturnal dosing with famotidine 20 mg is effective in preventing gastric ulcer relapse over a 1-year period and is well tolerated, it offers a therapeutic option for the long-term treatment of patients with gastric ulcer.     

法莫替丁治疗消化性溃疡

经胃镜证实活动性消化性溃疡用双盲对照法,23例(男21例,女2例,年龄41±11a)服法莫替丁20mg bid;另17例(男14例,女3例,年龄40±14a)服雷尼替丁150mg bid。十二指肠和胃溃疡分别于服药后4wk和6wk复查胃镜,结果法莫替丁显效率96％,雷尼替丁为94％,2组无显著差异。     

胃灵颗粒的研制及药理实验

目的 建立胃灵颗粒的制备工艺及质量控制方法，通过药理实验研究胃灵颗粒对消化性溃疡的愈合作用。方法 采用水煎煮提取方法制备胃灵颗粒，用薄层色谱法控制质量，用大鼠乙酸型慢性溃疡模型和幽门结扎胃液分析测定法，观察该药的抗溃疡作用和对胃溃疡愈合质量的影响。结果 胃灵颗粒可显著促进胃溃疡的愈合，且一少胃溃疡愈合创面再生组织的炎症细胞浸润，提高胃溃疡的愈合质量。结论 胃灵颗粒能有效提高消化性溃疡的愈合质量。     

Famotidine. Pharmacodynamic and pharmacokinetic properties and a preliminary review of its therapeutic use in peptic ulcer disease and Zollinger-Ellison syndrome

Famotidine is a new histamine H2-receptor antagonist. On a weight basis, famotidine is 20 times more potent than cimetidine and 7.5 times more potent than ranitidine in inhibiting basal and pentagastrin-stimulated gastric acid secretion in humans. Therapeutic trials have shown that famotidine 20 mg twice daily or 40 mg at bedtime may be an effective alternative to standard doses of cimetidine for healing gastric ulcers and to standard doses of cimetidine and ranitidine for healing duodenal ulcers. When used prophylactically, a single 20 mg dose of famotidine at night decreases the incidence of duodenal ulcer recurrence (versus placebo). However, further study is needed to clarify the comparative efficacy of the H2-receptor antagonists, in particular as maintenance therapy for healed peptic ulcer. Preliminary results in a few patients with Zollinger-Ellison syndrome indicate that famotidine, alone or in combination with an anticholinergic agent, gives good control of gastric acid hyperacidity with no evidence of biochemical or haematological toxicity. Famotidine appears to be well tolerated. Unlike cimetidine, it does not have antiandrogenic effects or alter hepatic metabolism of drugs. However, wider clinical experience with famotidine is needed to accurately determine its relative tolerability compared with other anti-ulcer drugs. Thus, famotidine appears to be a suitable and well tolerated alternative to cimetidine and ranitidine for healing peptic ulcers, but wider clinical experience is needed to assess its relative efficacy and tolerability in the long term maintenance treatment of patients with healed ulcers as well as in patients with Zollinger-Ellison syndrome.     

Pharmacological and therapeutic properties of lafutidine (stogar and protecadin), a novel histamine H2 receptor antagonist with gastroprotective activity]

Potent antisecretory agents, such as histamine H2-receptor antagonists and proton pump inhibitors, have achieved great improvement in peptic ulcer therapy. It has, however, been reported that incidence of ulcer relapse is high after discontinuation of these drugs. Insufficient efficacy against NSAID-induced ulcers is also critical. Lafutidine is a novel histamine H2 antagonist with gastroprotective activity. Lafutidine exhibited potent and long-lasting H2 antagonism and prolonged antisecretion. In addition, lafutidine showed a gastroprotective effect against noxious agents-induced gastric mucosal damage through capsaicin-sensitive afferent nerves. Lafutidine showed antiulcer activities against acute ulcer models, prevented gastric ulcer relapse of acetic ulcer, and accelerated the healing of indomethacin-induced antral ulcers in rats. These results suggest the advantage of the combined antisecretory and gastroprotective activities. In clinical studies, lafutidine showed prolonged antisecretion, healing effect against gastric and duodenal ulcers and gastritis, and its potency was equal or superior to that of conventional H2 antagonists. Additionally, lafutidine induced a high transition rate to the E0 stage determined by endoscopical ultrasonography, suggesting the high quality of ulcer healing. Furthermore, effectiveness of lafutidine against NSAIDs-induced ulcer was high. From these results, lafutidine is equal or superior to conventional H2 antagonists in antiulcer potency, and it may be useful for the prevention of ulcer relapse and or treatment of NSAIDs-induced gastroduodenal damage.