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Effects of omeprazole on intragastric pH and plasma gastrin are dependent on the CYP2C19 polymorphism

GASTROENTEROLOGY 2000年第3期119卷 670-676页

作者： Sagar, M Tybring, G Dahl, ML Bertilsson, L Seensalu, R St Gorans Hosp AB Dept Med S-11281 Stockholm Sweden Huddinge Univ Hosp Karolinska Inst Ctr Gastroenterol Dept Surg Stockholm Sweden Huddinge Univ Hosp Karolinska Inst Clin Res Ctr Dept Med Stockholm Sweden Huddinge Univ Hosp Karolinska Inst Dept Med Lab Sci & Technol Div Clin Pharmacol Stockholm Sweden

Background & Aims: Omeprazole is metabolized by cytochrome P450 (CYP2C19). The activity of this enzyme is polymorphic, with incidences of poor metabolizers (PMs), heterozygous extensive metabolizers (EMs), and homozygous EMs in white populations of 3%, 30%, and 67%, respectively. The importance of the CYP2C19 polymorphism for the effects of omeprazole on intragastric pH and plasma gastrin concentrations has been investigated, Methods: Twenty-five white patients were genotyped for CYP2C19 by allele-specific polymerase chain reaction amplification, and their Helicobacter pylori status was assessed by serology and with immunoblot analysis. Intragastric pH was monitored over 24 hours, and meal-stimulated plasma gastrin concentration was measured over 4 hours (AUC 4h) before (day 0) and during (day 8) treatment with 20 mg omeprazole once daily. Results: Eleven patients were homozygous for the wild-type allele (wt/wt), 12 were heterozygous EMs (wt/mut), and 2 were PMs (mut/mut), Median (95% confidence interval) 24-hour intragastric pH in the heterozygous EM group was 5.5 (range, 5.1-5.9) compared with 3.1 (range, 2.7-3.6) in homozygous EMs (P < 0.0001) at day 8. The percentage of time with intragastric pH > 4 at day 8 was significantly higher in the wt/mut than wt/wt group (72.4% vs. 37.1%;P < 0.0001). H. pylori status had less influence than CYP2C19 on intragastric acidity. Omeprazole treatment increased meal-stimulated plasma gastrin concentrations from day 0 to day 8 in the homozygous EMs and heterozygous EMs by 16% (NS) and 157% (P = 0.002), respectively. In heterozygous EMs, the gastrin increase was more pronounced in the H. pylori-positive group (226%) than H. pylori-negative group (80%;P = 0.02). Conclusions: The effects of omeprazole on intragastric pH and plasma gastrin are dependent on the CYP2C19 polymorphism in patients with acid-related disorders.

关键词：等位基因抗溃疡病药/治疗应用芳基烃羟化酶类细胞色素P450酶系统/遗传学胃酸/代谢胃泌素类/血液基因型幽门螺杆菌/分离和提纯杂合子纯合子氢离子浓度混合功能氧化酶类/遗传学奥美拉唑/治疗应用容积渗克分子浓度表型多态现象遗传/生理学胃疾病/药物疗法胃疾病/遗传学胃疾病/代谢胃疾病/微生物学老年人女(雌)性人类男(雄)性中年人

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Is Helicobacter pylori eradication associated with gastroesophageal reflux disease?

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AMERICAN JOURNAL OF GASTROENTEROLOGY 2000年第4期95卷 914-920页

作者： Fallone, CA Barkun, AN Friedman, G Mayrand, S Loo, V Beech, R Best, L Joseph, L McGill Univ Ctr Hlth Div Gastroenterol Montreal PQ Canada McGill Univ Ctr Hlth Div Epidemiol Montreal PQ Canada McGill Univ Ctr Hlth Div Biostat Montreal PQ Canada McGill Univ Inst Parasitol Montreal PQ Canada Dalhousie Univ Queen Elizabeth II Hlth Sci Ctr Halifax NS Canada

OBJECTIVES: A recent report has suggested an association between Helicobacter pylori eradication and the development of gastroesophageal reflux disease (GERD). We therefore assessed the incidence of GERD among comparable patients having undergone successful versus failed H. pylori eradication in a controlled trial. We also compared the H. pylori strains in the subjects that developed GERD to those that did not. METHODS: Patients with a history of proven duodenal ulcer and H. pylori infection were randomised into a H. pylori eradication study. Patients subsequently underwent gastroscopy with gastric biopsies every 3 months for 1 yr. At each visit, the presence of GERD symptoms and endoscopic esophagitis were noted, and the incidence of these variables among patients in whom H, pylori eradication was successful was compared to those in whom it was not. In a subgroup, the presence of the cagA, cagE, and vacA genotypes and of cagA antibodies were determined. RESULTS: Of 98 patients randomized into this study, 11 dropped out before determination of H. pylori eradication, leaving 87 patients with analyzable results. H, pylori eradication was successful in 63 (72%). By the end of the follow-up period, patients with GERD symptoms or endoscopic esophagitis were more prevalent in the successful than in the failed eradication group (37% [95% CI: 25-50%] vs 13% [95% CI: 3-32%], p = 0.04, 95% CI for the difference. 6-42%), as were patients with GERD symptoms alone (29% [95% CI: 18-41%] vs 8% [95% CI: 1-27%], p = 0.04, 95% CI for the difference: 4-36%) or esophagitis alone (21% [95% CI: 12-33%] vs 4% [95% CI: 0-21%], p = 0.10, 95% CI for the difference: 4-29%, respectively). Multivariate analysis revealed no significant association between the incidence of symptoms or esophagitis and age, Sender, Quetelet index, caffeine or alcohol intake, smoking, weight change, or the presence of a hiatus hernia. There were also no differences in the prevalence of H. pylori genotypes from patie

关键词：阿莫西林/治疗应用抗溃疡病药/治疗应用铋/治疗应用双盲法药物疗法联合十二指肠溃疡/药物疗法十二指肠溃疡/微生物学食管炎消化性/病因学食管炎消化性/微生物学随访研究胃食管反流/病因学胃食管反流/微生物学胃镜检查基因型螺杆菌感染/药物疗法螺杆菌感染/微生物学螺杆菌幽门/药物作用螺杆菌幽门/遗传学甲硝唑/治疗应用治疗失败青少年成年人老年人女(雌)性人类男(雄)性中年人

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Differentiation and proliferation in Barrett's esophagus and the effects of acid suppression

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GASTROENTEROLOGY 1999年第2期117卷 327-335页

作者： Ouatu-Lascar, R Fitzgerald, RC Triadafilopoulos, G Palo Alto Vet Affairs Hlth Care Syst Gastroenterol Sect 111GI Palo Alto CA 94304 USA Stanford Univ Sch Med Stanford Univ Hosp Div Gastroenterol Stanford CA 94305 USA

Background & Aims: Maintenance of normal epithelial differentiation and proliferation is an important goal in cancer chemoprevention. Because acid has a dynamic effect on cell proliferation/differentiation of Barrett's esophagus (BE) ex vivo, we investigated the relationship between differentiation, proliferation, and dysplasia in BE biopsy specimens and explored the role of normalization of intraesophageal pH in altering the BE phenotype. Methods: Endoscopic biopsy specimens of BE (with or without dysplasia) were analyzed for (1) villin, a differentiation marker, by immunoblotting;(2) proliferating cell nuclear antigen (PCNA), a proliferation marker, by immunohistochemistry;and (3) dysplasia by histology before and after 6 months of normalization of intraesophageal pH (confirmed by 24-hour pH monitoring) with lansoprazole. Results: At baseline, there was a negative correlation (r = -0.79) between villin and PCNA expression. Six months later, PCNA expression decreased and villin expression increased (P < 0.001) in 24 patients whose intraesophageal pH normalized. Fifteen patients had persistently pathological intraesophageal acid reflux and no change in villin or PCNA expression. There were no differences in the occurrence of dysplasia after 6 months in either group. Conclusions: In BE, there is an inverse relationship between villin and PCNA. In turn, dysplasia is unrelated to villin expression and well correlated with PCNA expression. Complete symptom eradication with lansoprazole does not guarantee normalization of intraesophageal pH profile in BE patients. Effective intraesophageal acid suppression favors differentiation and decreases proliferation. The intriguing possibility that acid suppression can be used to prevent dysplasia remains to be explored.

关键词： 2-吡啶甲基亚硫酰苯咪唑类抗溃疡病药/治疗应用 Barrett食管/药物疗法 Barrett食管/代谢 Barrett食管/病理学载体蛋白质类/分析细胞分化/药物作用细胞分裂/药物作用胃酸/代谢氢离子浓度免疫印迹法免疫组织化学微丝蛋白质类/分析奥美拉唑/类似物和衍生物奥美拉唑/治疗应用增殖细胞核抗原/分析成年人老年人老年人 80以上女(雌)性人类男(雄)性中年人

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The long-term reinfection rate and the course of duodenal ulcer disease after eradication of Helicobacter pylori in a developing country

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AMERICAN JOURNAL OF GASTROENTEROLOGY 2000年第1期95卷 50-56页

作者： Rollan, A Giancaspero, R Fuster, F Acevedo, C Figueroa, C Hola, K Schulz, M Duarte, I Hosp Naval Almirante Nef Dept Gastroenterol Vina Del Mar Chile Pontificia Univ Catolica Chile Fac Med Dept Gastroenterol & Pathol Santiago Chile

OBJECTIVE: The aim of this study was to evaluate the effect of Helicobacter pylori (H. pylori) eradication on the natural history of duodenal ulcer disease and the reinfection rate after treatment in a developing country. METHODS: A total of 111 H. pylori-infected patients with duodenal ulcer were treated with either omeprazole or famotidine plus two antibiotics for 2 wk. Those failed to respond to treatment were retreated with bismuth-based triple therapy. RESULTS: The radication rate was 76% (95% CI: 67-83%). Eventually, H. pylori was eradicated in 96 of the 111 patients (86%), who were followed-up clinically and endoscopically for a mean of 37.2 months. The cumulative reinfection rate after eradication (Kaplan-Meier) was 8% +/- 3% in yr 1, 11% +/- 4% in yr 2, and 13% +/- 4% in yr 3. Nine of the 12 reinfections occurred during yr 1. Recurrence of duodenal ulcer was detected in five patients (5.2%), all of them during yr 1 of follow-up. Histologically, gastritis scores (according to the Sydney system) improved significantly after eradication. CONCLUSIONS: In a high prevalence setting, H. pylori eradication and early reinfection rates after treatment are similar to rates observed in a low prevalence environment, whereas the late reinfection rate seems to be higher. However, up to 3 yr after treatment, most treated patients are free of H. pylori infection and/or ulcer activity. Even longer follow-up studies are necessary to determine whether specific retreatment policies are necessary to maintain long term eradication in developing countries.

关键词：阿莫西林/投药和剂量抗溃疡病药/治疗应用智利发展中国家药物疗法联合/投药和剂量十二指肠溃疡/诊断十二指肠溃疡/药物疗法十二指肠溃疡/微生物学法莫替丁/治疗应用随访研究胃炎/诊断胃炎/微生物学螺杆菌感染/并发症螺杆菌感染/诊断螺杆菌感染/药物疗法螺杆菌幽门甲硝唑/投药和剂量奥美拉唑/治疗应用复发替硝唑/投药和剂量青少年成年人老年人女(雌)性人类男(雄)性中年人

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Association of heparin with basic fibroblast growth factor, epidermal growth factor, and constitutive nitric oxide synthase on healing of gastric ulcer in rats

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 1999年第2期290卷 789-796页

作者： Li, Y Wang, HY Cho, CH Univ Hong Kong Fac Med Dept Pharmacol Hong Kong Peoples R China

The healing effect of heparin on gastric ulcer and its underlying mechanisms were studied. The influences of protamine on these effects were also investigated. Gastric ulcer was induced by acetic acid in rats. Heparin (100-1000 U/kg i.v.) was given once daily for 4 or 7 days. Ulcer area was measured;gastric mucosal regeneration, proliferation, and angiogenesis were determined by histological or immunohistochemical methods. Gastric mucosal basic fibroblast growth factor (bFGF) level was assessed by an enzyme-linked immunosorbent assay, and the mucosal epidermal growth factor (EGF) level and nitric oxide synthase (NOS) activity were measured by radioimmunoassay. The anticoagulant action of heparin was determined by the duration of bleeding time. The results showed that heparin given for 4 or 7 days significantly accelerated gastric ulcer healing in a dose-dependent manner. The three doses of heparin significantly stimulated mucosal regeneration and proliferation as well as angiogenesis but not the contraction of ulcer base. Similar effects were observed in gastric mucosal bFGF and EGF levels and constitutive NOS activity. Protamine not only abolished the anticoagulant action of heparin but also significantly potentiated its effects on ulcer healing, gastric mucosal proliferation, angiogenesis, and constitutive NOS activity. These findings indicate that heparin can accelerate gastric ulcer healing, which is associated with mucosal regeneration, proliferation, and angiogenesis. These actions are likely to be stimulated by bFGF, EGF, and constitutive NOS activity in the gastric mucosa. Protamine potentiates the ulcer-healing effect of heparin, which is probably acting through constitutive NOS activation.

关键词：醋酸类抗溃疡病药/治疗应用抗凝药/治疗应用血液凝固/药物作用细胞分裂/药物作用表皮生长因子/代谢表皮生长因子/生理学上皮细胞/药物作用成纤维细胞生长因子2/代谢成纤维细胞生长因子2/生理学胃黏膜/药物作用胃黏膜/酶学胃黏膜/代谢肝素/治疗应用肝素拮抗药/药理学新生血管化生理性/药物作用一氧化氮合酶/拮抗剂和抑制剂一氧化氮合酶Ⅰ型鱼精蛋白类/药理学大鼠 Sprague-Dawley 胃溃疡/血液胃溃疡/化学诱导胃溃疡/病理学动物男(雄)性大鼠

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Usefulness of serological IgG antibody determinations for confirming eradication of Helicobacter pylori infection

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AMERICAN JOURNAL OF GASTROENTEROLOGY 1999年第8期94卷 2105-2108页

作者： Marchildon, P Balaban, DH Sue, M Charles, C Doobay, R Passaretti, N Peacock, J Marshall, BJ Peura, DA Enter Prod Inc Stony Brook NY 11790 USA Univ Virginia Charlottesville VA USA Univ Guyana Turkeyen Guyana

OBJECTIVE: Prior studies have suggested that IgG antibody titers may be useful to confirm successful treatment of Helicobacter pylori (H. pylori) infection. However, the diagnostic value of decreasing IgG titers is limited by the necessity to perform pre and posttreatment tests in parallel which requires stored sera. Our objective was to assess the accuracy of IgG antibody titers using the HM-CAP IgG EIA kit (Enteric Products) in monitoring treatment of H. pylori infection and to compare the relative accuracy of parallel versus serial determinations. METHODS: The C-14 urea breath test (UBT) was used to confirm H. pylori infection in 83 dyspeptic patients and eradication of the organism at 4 wk and 6 months posttreatment. IgG titers pretherapy and 6 months posttherapy were determined either serially (separate EIA plates) or in parallel (same ELA plate), and the relative percent decline in antibody titer was calculated. RESULTS: When a decline of greater than or equal to 25% at 6 months was used as the cut-off for H. pylori eradication, mean sensitivities of serial and parallel determinations were 87.5% and 86.8%, respectively, and mean specificities of both were 100%. In 68 of 75 patients in whom the organism was eradicated, the mean decrease in IgG titer at 6 months was 41.1% for serial determinations and 41.5% for parallel determinations. CONCLUSIONS: Serial or parallel IgG titers offer equivalent diagnostic accuracy for confirming H. pylori eradication after therapy. A greater than or equal to 25% decline in titer 6 months after therapy is a sensitive and specific marker for eradication of the infection. Serial evaluation of IgG titers does not require serum storage, and is a cost-effective and accurate alternative to the UBT or endoscopy-based methods. (Am J Gastroenterol 1999;94:2105-2108. (C) 1999 by Am. Coll. of Gastroenterology).

关键词：抗菌药/治疗应用抗溃疡病药/治疗应用抗体细菌/血液呼吸试验药物疗法联合随访研究胃炎/诊断胃炎/药物疗法胃炎/免疫学螺杆菌感染/诊断螺杆菌感染/药物疗法螺杆菌感染/免疫学螺杆菌幽门/药物作用螺杆菌幽门/免疫学免疫球蛋白G/血液敏感性与特异性青少年成年人老年人女(雌)性人类男(雄)性中年人

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Pantoprazole versus ranitidine in the treatment of duodenal ulcer:: A multicenter study in Brazil

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AMERICAN JOURNAL OF GASTROENTEROLOGY 2000年第1期95卷 62-66页

作者： Meneghelli, UG Zaterka, S Castro, LD Malafaia, O Lyra, LGC Univ Sao Paulo Med Sch Ribeirao Preto Dept Med Div Gastroenterol Ribeirao Preto SP Brazil Univ Sao Paulo Dept Gastroenterol Campinas SP Brazil UNICAMP Campinas SP Brazil Univ Fed Minas Gerais Dept Gastroenterol Belo Horizonte MG Brazil Hosp Evangel Curitiba Parana Brazil Univ Fed Bahia Salvador BA Brazil S Rafael Hosp Internal Med Serv Salvador BA Brazil

OBJECTIVE: The aim of this study was to compare the effectiveness and tolerance of pantoprazole versus ranitidine in the treatment of duodenal ulcers in the Brazilian population. METHODS: A total of 222 patients with active duodenal ulcers (DU) were randomly allocated to a double dummy blind treatment, either with ranitidine (RAN) 300 mg (111, aged from 20-68 yr old, 56 female) or with pantoprazole (PANT) 40 mg (111 patients, 18-70 yr old, 45 female). After a 2-wk course of treatment, each patient was clinically and endoscopically assessed for ulcer healing. Failure to heal required a further 2-wk course of treatment and a new evaluation thereafter. RESULTS: In all, 77 of the 103 patients in the PANT group (74.8%) and 42 of the 94 patients in the RAN group (44.7%) who completed the study had ulcer healing after one 2-wk treatment course, and an additional 23 in the PANT group (22.3%) and 28 in the RAN group (29.8%) after the second 2-wk treatment course, totaling 100 (97.1%) and 70 (74.5%), respectively. Therapeutic gain in favor of pantoprazole was significant both at the end of the first and the second 2-wk treatment course (p < 0.001). At 2 wk, symptoms remission was significantly higher in the PANT group (97.6%) than with the RAN group (77.5%) (p < 0.001). The Intention-to-treat analysis showed results statistically similar to those observed in the per-protocol analysis. Minor adverse events were reported by four patients in the PANT group and three in the RAN group. No relevant laboratory abnormalities were seen. No patient withdrew from the study due to adverse events. CONCLUSIONS: Our results show that pantoprazole is more effective than ranitidine in the treatment of duodenal ulcer providing faster ulcer healing in most patients (97.1%), in 4 wk. Adverse events were rare and were similar in both groups, and had no influence on the therapeutic outcome.

关键词： 2-吡啶甲基亚硫酰苯咪唑类抗溃疡病药/治疗应用苯咪唑类/治疗应用双盲法十二指肠溃疡/药物疗法组胺H2拮抗剂/治疗应用奥美拉唑/类似物和衍生物雷尼替丁/治疗应用亚砜类/治疗应用青少年成年人老年人女(雌)性人类男(雄)性中年人

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Rabeprazole is superior to ranitidine in the management of active duodenal ulcer disease: Results of a double-blind, randomized North American study

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AMERICAN JOURNAL OF GASTROENTEROLOGY 2000年第4期95卷 936-942页

作者： Breiter, JR Riff, D Humphries, TJ Eisai & Co Ltd Princeton NJ 08540 USA Manchester Mem Hosp Manchester CT USA Associated Gastroenterol Med Grp Anaheim CA USA

OBJECTIVE: The primary purpose of this study was to compare the efficacy and tolerability of rabeprazole versus ranitidine in the treatment of patients with active duodenal ulcer disease. METHODS:This multicenter, double-blind, randomized, parallel-group study enrolled 376 patients. Patients were randomly assigned to receive rabeprazole 20 mg administered once daily in the morning (q.a.m.) with matching ranitidine placebo twice daily (b.i.d.) (n = 188), or ranitidine 150 mg b.i.d. with matching rabeprazole placebo q.a.m. (n = 188). Three visits were scheduled: wk 0 (baseline;days -3 to -1), wk 2 (day 15 +/- 3 days), and wk 3 (day 29 +/- 3 days). The primary efficacy response variable was defined as complete regeneration of the mucose at the site of all ulcers identified during the study. Secondary efficacy variables included patients' ratings of frequency and severity of ulcer pain, frequency of antacid use, and improvement of overall physical well-being. Tolerability was evaluated with analyses of adverse events, laboratory evaluations, fasting serum gastrin levels, vital signs, body weight, and electrocardiograms. RESULTS: Up to 4 wk of treatment with rabeprazole 20 mg q.a.m. produced significantly greater healing rates, compared to treatment with ranitidine150 mg b.i.d. (83% vs 73%;p = 0.017). Significant differences between treatment groups were also observed for secondary efficacy indices. At wk 2, rabeprazole was more likely than ranitidine to produce complete resolution of duodenal ulcer pain (39% vs 25%;p = 0.006), improvement in duodenal ulcer nighttime pain severity (76% vs 65%;p = 0.044), and improvement in overall well-being (55% vs 41%;p = 0.009). At wk 4, the proportion of patients with normalization of overall wellbeing was significantly higher in the rabeprazole group than in the ranitidine group (45% vs 29%;p = 0.003). Rabeprazole was safe and well tolerated in this study. CONCLUSIONS: In patients with active duodenal ulcer disease, rabeprazole 20 m

关键词： 2-吡啶甲基亚硫酰苯咪唑类抗溃疡病药/治疗应用苯咪唑类/治疗应用双盲法十二指肠溃疡/药物疗法十二指肠镜检查奥美拉唑/类似物和衍生物疼痛测定雷尼替丁/治疗应用治疗结果青少年成年人老年人老年人 80以上女(雌)性人类男(雄)性中年人

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Gastrointestinal pharmacology

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VETERINARY CLINICS OF NORTH AMERICA-EQUINE PRACTICE 1999年第3期15卷 535-+页

作者： Freeman, DE Univ Illinois Coll Vet Med Urbana IL 61802 USA

Diseases of the gastrointestinal tract that require pharmacologic management, usually in combination with other treatments, are gastric ulcers (omeprazole and others), colic (laxatives, analgesics), diarrhea (antibiotics, protectants and absorbents, glucocorticoids, motility inhibitors), reperfusion injury, postoperative ileus (prokinetic drugs), and adhesions. There is growing evidence that nonsteroidal anti-inflammatory drugs can alter important physiologic properties of the intestine;however, these drugs are valuable analgesics for horses and their use should be tempered with an awareness of their harmful effects. The role of antibiotics in treating gastrointestinal disease is controversial, but their ability to induce life-threatening diarrhea is well known and invites caution and defensible use of these drugs in horses.

关键词：抗菌药/治疗应用消炎药非甾类/治疗应用抗溃疡病药/治疗应用泻药/治疗应用胆碱能药/治疗应用酶抑制剂/治疗应用胃肠病用药/治疗应用胃肠疾病/药物疗法胃肠疾病/兽医学组胺H2拮抗剂/治疗应用马疾病/药物疗法马动物

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Systematic review of the cost effectiveness of prophylactic treatments in the prevention of gastropathy in patients with rheumatoid arthritis or osteoarthritis taking non-steroidal anti-inflammatory drugs

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ANNALS OF THE RHEUMATIC DISEASES 2000年第10期59卷 753-759页

作者： van Dieten, HEM Korthals-de Bos, IBC van Tulder, MW Lems, WF Dijkmans, BAC Boers, M Free Univ Amsterdam Dept Clin Epidemiol & Biostat NL-1081 BT Amsterdam Netherlands Free Univ Amsterdam Dept Rheumatol NL-1081 BT Amsterdam Netherlands

A systematic review on the cost effectiveness of prophylactic treatments of nonsteroidal anti-inflammatory drug (NSAID) induced gastropathy in patients with osteoarthritis or rheumatoid arthritis was conducted. Two reviewers conducted the literature search and the review. Both full and partial economic evaluations published in English, Dutch, or German were included. The criteria list published in the textbook of Drummond was used to determine the quality of the economic evaluations. The methodological quality of three randomised controlled trials (RCTs) in which the economic evaluations obtained probability estimates of NSAID induced gastropathy and adverse events was assessed by a list of internal validity criteria. The conclusions were based on a rating system consisting of four levels of evidence. Ten economic evaluations were included;three were based on RCTs. All evaluations studied misoprostol as prophylactic treatment: in one evaluation misoprostol was studied as a fixed component in a combination with diclofenac (Arthrotec). All economic evaluations comprised analytical studies containing a decision tree. The three trials were of high methodological quality. Nine economic evaluations were considered high quality and one economic evaluation was considered of low methodological quality. There is strong evidence (level "A") that the use of misoprostol for the prevention of NSAID induced gastropathy is cost effective, and limited evidence (level "C") that the use of Arthrotec is cost effective. Although the levels of evidence used in this review are arbitrary, it is believed that a qualitative analysis is useful: quantitative analyses in this field are hampered by the heterogeneity of economic evaluations. Existing criteria to evaluate the methodological quality of economic evaluations may need refinement for use in systematic reviews.

关键词：消炎药非甾类/治疗应用抗溃疡病药/经济学抗溃疡病药/治疗应用关节炎类风湿/药物疗法费用效益分析胃肠疾病/化学诱导胃肠疾病/药物疗法胃肠疾病/经济学米索前列醇/经济学米索前列醇/治疗应用骨关节炎/药物疗法人类

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