The Choice of Proton Pump Inhibitor: Does it matter?

Proton pump inhibitors are used at different dosages for the treatment of acid-related gastrointestinal disorders, such as gastro-oesophaeal reflux and peptic ulcer disease. Comparisons of four different proton pump inhibitors: lansoprazole, omeprazole, pantoprazole, and rabeprazole show that they all have similar potency and efficacy. Rabeprazole, however, displays a slightly more rapid onset of acid inhibition than the others; the clinical advantage of this seems limited. The S-isomer of omeprazole, esomeprazole, exhibits a somewhat higher potency than the other proton pump inhibitors. Reports supporting a clinical advantage of this property are not convincing. To conclude, all inhibitors seem comparable as regards inhibition of gastric acid secretion.     

Comparative study of proton pump inhibitors on dexamethasone plus pylorus ligation induced ulcer model in rats

The present study was designed to compare ulcer protective effect of proton pump inhibitors viz. omeprazole, rabeprazole and lansoprazole against dexamethasone plus pylorus ligation induced ulcer model. Dexamethasone (5 mg/kg) was used as an ulcerogen. Dexamethasone suspended in 1% CMC in water was given orally to all the rats 15 min after the pylorus ligation. Omeprazole (20 mg/kg), rabeprazole (20 mg/kg), and lansoprazole (20 mg/kg) were administered by oral route 30 min prior to ligation was used for ulcer protective studies, gastric secretion and mucosal studies. Effects of proton pump inhibitors were determined by the evaluation of various biochemical parameters such as ulcer index, free and total acidity, gastric pH, mucin, pepsin and total proteins. Oral administration of proton pump inhibitors showed significant reduction in gastric acid secretion and ulcer protective activity against dexamethasone plus pylorus ligation induced ulcer model. The % protection of omeprazole, rabeprazole and lansoprazole was 84.04, 89.36 and 79.78, respectively. Rabeprazole significantly inhibited the acid-pepsin secretion and increased the gastric mucin secretion. The observations made in the present study suggest that rabeprazole is the most effective gastric antisecretory and ulcer healing agent as compared to omeprazole and lansoprazole.     

Review article: the pharmacology of rabeprazole

Rabeprazole sodium is a new substituted benzimidazole proton pump inhibitor with several differences compared with existing proton pump inhibitors. In vitro and animal studies have demonstrated that rabeprazole is a more potent inhibitor of H⁺,K⁺-ATPase and acid secretion than omeprazole, and is a more rapid inhibitor of proton pumps than omeprazole, lansoprazole, or pantoprazole. This probably reflects rabeprazole's faster activation in the parietal cell canaliculus. In human studies, once-daily doses of 5–40 mg of rabeprazole inhibit gastric acid secretion in a dose-dependent fashion. A once-daily dose of 20 mg has consistently achieved profound decreases in 24-h intragastric acidity in single and repeat dosing studies, in healthy volunteers and patients with either peptic ulcer disease or gastro-oesophageal reflux disease. Significantly greater decreases in intragastric acidity are achieved on day 1 of dosing with rabeprazole 20 mg than with omeprazole 20 mg. As with other proton pump inhibitors, rabeprazole has in vitro antibacterial activity against Helicobacter pylori , with greater activity against this organism than either lansoprazole or omeprazole. In addition to inhibiting bacterial urease activity, rabeprazole binds to several molecules on H. pylori . Clinical trials are needed to assess the clinical importance of these findings, as well as to assess whether the potential advantages of rabeprazole result in clinical benefit for patients with acid-related diseases.     

Influence of proton pump inhibitors on dexamethasone-induced gastric mucosal damage in rats

The present study was designed to compare the curative role of proton pump inhibitors, omeprazole, rabeprazole and lansoprazole against dexamethasone-induced ulcer model. Dexamethasone (5 mg/kg/day) was used as an ulcerogen. Dexamethasone suspended in 1% CMC in water was given orally to all rats. Omeprazole (20 mg/kg), rabeprazole (20 mg/kg), and lansoprazole (20 mg/kg) were administered by oral route 30 minutes prior to dexamethasone for ulcer protective studies, gastric secretion and mucosal studies. Effects of proton pump inhibitors were determined by the evaluation of various biochemical parameters such as estimation of myeloperoxidase, cortisol, alkaline phosphatase, malondialdehyde, endogenous anti-oxidants like superoxide dismutase, catalase and reduced glutathione. In dexamethasone induced ulcer model, omeprazole showed significant decrease in malondialdehyde, myeloperoxidase, alkaline phosphatase level and increase in superoxide dismutase, catalase and reduced glutathione level as compared to rabeprazole and lansoprazole. Omeprazole showed significant reduction in cortisol content where as rabeprazole and lansoprazole did not show significant changes as compared to control. The result indicates that omeprazole is the most effective and selective proton pump inhibitor in dexamethasone induced ulcer model as compared to rabeprazole and lansoprazole.     

Rabeprazole: an update of its use in acid-related disorders.

Rabeprazole is an inhibitor of the gastric proton pump. It causes dose-dependent inhibition of acid secretion. In 8-week studies, among patients with gastro-oesophageal reflux disease (GORD), rabeprazole 20 mg/day or 10mg twice daily was as effective as omeprazole and superior to ranitidine in the healing of GORD. Symptom relief with rabeprazole was superior to that provided by placebo and ranitidine and similar to omeprazole. In long-term trials rabeprazole 10 mg/day was similar to omeprazole 20 mg/day in a 2-year study and superior to placebo in 1-year studies, in both the maintenance of healing and prevention of symptoms in patients with healed GORD. In nonerosive GORD, 4-week studies have shown rabeprazole to be more effective than placebo in relieving heartburn and various other gastrointestinal symptoms. Data among patients with Barrett's oesophagus suggest rabeprazole 20 mg/day may be more effective than placebo in maintaining healing of associated oesophagitis after 1 year of treatment. One-week triple Helicobacter pylori eradication therapy with rabeprazole plus clarithromycin and amoxicillin achieved eradication rates of > or =85%. Rabeprazole is as effective as omeprazole and lansoprazole when included as part of a triple-therapy regimen for the eradication of H. pylori. Eradication rates of >90% were achieved when rabeprazole 20 to 40 mg/day was included as part of a quadruple eradication regimen. As monotherapy for peptic ulcer healing and symptom relief, 4- to 8-week studies have shown rabeprazole 10 to 40 mg/day to be superior to placebo and ranitidine and have similar efficacy to omeprazole. Preliminary 1-year data among 16 patients with Zollinger-Ellison syndrome suggest rabeprazole 60 to 120 mg/day can resolve and prevent the recurrence of symptoms and endoscopic lesions associated with this condition. In clinical trials of up to 2 years' duration the tolerability of rabeprazole is similar to that of placebo, ranitidine and omeprazole. Common adverse events assigned to rabeprazole have been diarrhoea, headache, rhinitis, nausea, pharyngitis and abdominal pain. Histological changes and increases in serum gastrin levels were unremarkable and typical of proton pump inhibitors. No dosage adjustment is necessary in renal and mild to moderate hepatic impairment. CONCLUSION: Rabeprazole is a well tolerated proton pump inhibitor. It has proven efficacy in healing, symptom relief and prevention of relapse of peptic ulcers and GORD and can form part of effective H. pylori eradication regimens. It is an important alternative to H(2) antagonists and an additional treatment option to other proton pump inhibitors in the management of acid-related disorders.     

Comparison of rabeprazole 20 mg versus omeprazole 20 mg in the treatment of active duodenal ulcer: a European multicentre study

BACKGROUND: Rabeprazole sodium is the newest member of a class of substituted benzimidazole molecules known as proton pump inhibitors. Other proton pump inhibitors have been shown to be effective in healing active duodenal ulcer. METHOD: This randomized, double-blind, multicentre study, conducted at 25 European sites, compared the efficacy and tolerability of rabeprazole and omeprazole in patients with active duodenal ulcers. One hundred and two patients with active duodenal ulcer received rabeprazole 20 mg and 103 patients omeprazole 20 mg once daily for 2 or 4 weeks, with ulcer healing monitored by endoscopy. RESULTS: After 2 weeks, complete ulcer healing was documented in 69% of patients given rabeprazole 20 mg and in 62% of patients given omeprazole 20 mg (N.S.). After 4 weeks, healing rates were 98% in the rabeprazole group and 93% in the omeprazole group (P = 0.083). Rabeprazole-treated patients had significantly greater improvement in daytime pain symptom relief than those treated with omeprazole at the conclusion of the study (P = 0.038). Both drugs were well tolerated over the 4-week treatment period. Mean changes from baseline to end-point in fasting serum gastrin were significantly greater in the rabeprazole group, but at end-point mean values were well within normal limits for both groups. No clinically meaningful changes or other between-group differences were observed in laboratory parameters. CONCLUSION: In this study, rabeprazole produced healing rates equivalent to omeprazole at weeks 2 and 4, and provided significantly greater improvement in daytime pain. Both treatments were well tolerated.     

Review article: rabeprazole's tolerability profile in clinical trials

Rabeprazole is a new member of a class of substituted benzimidazole drugs known as proton pump inhibitors. Comparative trials have demonstrated that it is at least as effective as omeprazole for the treatment of gastro-oesophageal reflux disease (GERD), duodenal ulcers, or gastric ulcers. It is significantly more effective than histamine₂-receptor antagonists for acid suppression, GERD healing and pain relief, and duodenal ulcer healing and pain relief. Adverse events reported during clinical trials provide an important indication of a medication's tolerability. We demonstrate that rabeprazole has a favourable adverse events profile. It is well tolerated in placebo-controlled studies and comparative trials with omeprazole and H₂-receptor antagonists. Moreover, no dose adjustments are required for special populations, such as the elderly or patients with renal or mild-to-moderate hepatic disease. Adverse events data from clinical trials support the use of rabeprazole as a treatment for acid-related diseases.     

Rabeprazole: a pharmacologic and clinical review for acid-related disorders

Rabeprazole is a proton pump inhibitor that can be used in the treatment of acid-peptic-related disorders (gastroesophageal reflux disease [GERD], duodenal ulcer, gastric ulcer, gastric acid hypersecretory syndromes) and Helicobacter pylori. Pharmacodynamic data has demonstrated that rabeprazole, with a high pKa of ～ 5.0, can be activated at a higher pH than other proton pump inhibitors. This possibly results in faster onset of action. Owing to its non-enzymatic pathway of metabolism, rabeprazole is also less influenced by genetic polymorphisms of the CYP2C19, which others proton pump inhibitors are dependent on. In a 2-week, placebo-controlled trial, rabeprazole was both rapid and effective in relieving heartburn on day 1 of therapy and improved other GERD-related symptoms including regurgitation, belching, bloating, early satiety and nausea. For oesophageal reflux disease without erosions both 10 and 20 mg of rabeprazole are equivalent and better than placebo at 2 and 4 weeks. An on-demand approach to non-erosive reflux disease with 10 mg of rabeprazole has also been documented as superior to placebo. Some success in the treatment of extra-oesophageal manifestations of GERD, such as asthma and chronic laryngitis, has also been achieved with rabeprazole. Overall, rabeprazole with very few side effects is a safe and efficacious medication for acid suppression therapy.     

4种质子泵抑制剂治疗胃食管反流病的临床观察

目的:比较4种质子泵抑制剂埃索美拉唑(esomeprazole)、奥美拉唑(omeprazole)、兰索拉唑(lansoprazole)和雷贝拉唑(rabeprazole)对胃食管反流病(GERD)患者,在胃酸分泌、控制症状、治愈食管炎等方面的影响。方法:将经胃镜诊断明确的124例GERD患者随机分为A,B,C,D 4组,分别给予埃索美拉唑40 mg·d~(-1),奥美拉唑40 mg·d~(-1),兰索拉唑30 mg·d~(-1),雷贝拉唑20 mg·d~(-1),qd,疗程均为4周。结果:4种质子泵抑制剂症状缓解率分别为93.1%,81.6%,85.7%和86.4%,内镜下食管炎治愈率在70%以上(P<0.05)。结论:埃索美拉唑在症状缓解率和内镜下食管炎治愈率明显优于其他3种质子泵抑制剂。     

Rabeprazole: a review of its use in acid-related gastrointestinal disorders.

Rabeprazole is an inhibitor of the gastric proton pump. It causes dose-dependent inhibition of acid secretion and has a more rapid onset of action than omeprazole. Duodenal ulcers healed faster after treatment with rabeprazole 20 or 40 mg/day than placebo or ranitidine 150 mg 4 times daily and at a generally similar rate to omeprazole 20 mg/day in patients with duodenal ulcers; rabeprazole was similar or superior to these agents in relieving symptoms. Rabeprazole 20 and 40 mg/day healed gastric ulcers faster than placebo, and rabeprazole 20 mg/day healed ulcers at a similar healing rate, to omeprazole 20 mg/day in well controlled 6-week studies. Gastric ulcer symptom relief with rabeprazole was similar or superior to that provided by omeprazole or placebo. In 8-week studies in patients with gastro-oesophageal reflux disease (GERD), rabeprazole 10, 20 and 40 mg/day were more effective than placebo, rabeprazole 20 mg/day was more effective than ranitidine 150 mg twice daily, and rabeprazole 20 mg/day was similar in efficacy to omeprazole 20 mg/day. Symptom relief with rabeprazole in 8-week trials in patients with GERD was superior to that provided by placebo, and similar to ranitidine or omeprazole. Rabeprazole was similar to omeprazole and superior to placebo in both maintenance of healing and prevention of symptoms in patients with healed GERD in 1-year studies. One-week triple therapy with rabeprazole 20 mg twice daily plus 2 antibacterial agents achieved > or = 90% Helicobacter pylori eradication, but, as would be expected, a regimen of rabeprazole 20 mg twice daily plus 1 antibacterial agent was less successful. The drug was as effective as omeprazole and lansoprazole as part of triple therapy for H. pylori eradication. Rabeprazole successfully reduced acid output to target levels and prevented further pathological changes in 10 patients with Zollinger-Ellison syndrome. Usual dosages of rabeprazole are 20 mg/day for 4 weeks to treat duodenal ulcers, 6 weeks for gastric ulcers and 8 weeks for GERD, although some patients with duodenal ulcer may respond to a 10 mg/day dosage. For long term maintenance of GERD healing, 10 or 20 mg daily doses are adequate. Patients with hypersecretory states may need individualised dosages starting at 60 mg/day. The drug was well tolerated in clinical trials, with headache, rash, infection, diarrhoea and flu syndrome as the most common adverse events. In conclusion, rabeprazole appears to be a well tolerated proton pump inhibitor with a rapid onset of action and a low potential for drug interactions. The drug may be used to achieve healing and the relief of symptoms of duodenal ulcer, gastric ulcer and GERD, maintain GERD healing, and can form part of effective regimens to eradicate H. pylori.     

Systematic review: Rabeprazole-based therapies in Helicobacter pylori eradication

AIM: To perform a systematic review of the efficacy of rabeprazole-based therapies in Helicobacter pylori eradication, and to conduct a meta-analysis comparing the efficacy of rabeprazole and other proton pump inhibitors when co-prescribed with antibiotics. METHODS: Studies evaluating rabeprazole plus antibiotics were considered. Only randomized trials comparing rabeprazole and other proton pump inhibitors with antibiotics, and differing only in the proton pump inhibitor, were included in the meta-analysis. Electronic and manual bibliographic searches were conducted. The percentage (weighted mean) of successful eradication was calculated. Meta-analysis was performed by combining the odds ratios (OR) of the individual studies. RESULTS: The eradication rates were as follows: 14-day rabeprazole-amoxicillin, 73%; rabeprazole-amoxicillin-clarithromycin for 3, 5, 7 and 10 days, 44%, 72%, 78% and 75%, respectively; low-dose rabeprazole (20 mg/day), amoxicillin and clarithromycin for 7 days, 81%; high-dose rabeprazole (40 mg/day), amoxicillin and clarithromycin for 7 days, 75%; 7-day rabeprazole-clarithromycin-nitroimidazole, 85%. Twelve comparative studies were included in the meta-analysis. The eradication rate with rabeprazole plus antibiotics was 79%; it was 77% with other proton pump inhibitors (OR = 1.15; 95% confidence interval, 0.93-1.42). Sub-analysis comparing rabeprazole at low doses (10 mg b.d.) with other proton pump inhibitors at standard doses (omeprazole 20 mg b.d. or lansoprazole 30 mg b.d.) showed no differences. CONCLUSIONS: Rabeprazole achieves similar H. pylori eradication rates to omeprazole and lansoprazole when co-prescribed with antibiotics. Low doses of rabeprazole (10 mg b.d.), when administered with two antibiotics, may be sufficient to eradicate H. pylori infection.     

Decreasing oesophageal acid exposure in patients with GERD: a comparison of rabeprazole and omeprazole

BACKGROUND: Rabeprazole has been shown to be more potent and faster than other proton pump inhibitors in in vitro studies and highly effective in decreasing oesophageal acid exposure in patients with gastro-oesophageal reflux disease (GERD). AIM: This study was a multicentre, double-blind, placebo-controlled, randomized, parallel-group comparison of three active treatment regimens utilizing two different proton pump inhibitors, or placebo, administered over 7 days in patients with GERD. METHODS: Eighty-two patients with symptomatic GERD were given placebo, rabeprazole 10 mg b.d., rabeprazole 20 mg o.m., or omeprazole 20 mg o.m. for 7 days. Twenty-four hour oesophageal pH monitoring was performed at baseline and repeated at the conclusion of the treatment period. RESULTS: At the end of study, the percentage time (mean +/- s.d.) with pH < 4 over a 24-h period was significantly decreased by the three active regimens but without significant difference between them (9.27 +/- 4.77; 2.53 +/- 4.27; 2.02 +/- 1.71 and 2.91 +/- 4.06 for placebo, rabeprazole 10 mg b.d., rabeprazole 20 mg o.m. and omeprazole 20 mg o.m., respectively). Acid exposure was normalized in 90% of patients treated with rabeprazole 10 mg b.d., 95% treated with rabeprazole 20 mg o.m., 78% treated with omeprazole 20 mg o.m., and only 9.5% of patients treated with placebo. Both rabeprazole and omeprazole were well-tolerated. CONCLUSIONS: Although rabeprazole 20 mg o.m. showed greater activity numerically, this study demonstrates that rabeprazole 10 mg b.d. and 20 mg o.m. are equivalent to omeprazole 20 mg o.m. in decreasing oesophageal acid exposure.     

Acid inhibition on the first day of dosing: comparison of four proton pump inhibitors

BACKGROUND: Rapid and consistent acid suppression on the first day of dosing may be important in treating acid-related disorders. AIM: To compare the antisecretory activity and onset of action of single doses of rabeprazole, lansoprazole, pantoprazole, omeprazole capsule, omeprazole multiple unit pellet system (MUPS) tablet and placebo in healthy Helicobacter pylori-negative subjects. METHODS: This cross-over, double-blind, randomized study was performed in 18 H. pylori-negative subjects. Twenty-four-hour intragastric pH monitoring was performed on the day of treatment (once-daily dose of rabeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg, omeprazole capsule 20 mg, omeprazole MUPS tablet 20 mg or placebo). RESULTS: The intragastric pH (3.4) and time at pH > 4 during the 24 h post-dose (8.0 h) were significantly greater with rabeprazole than with lansoprazole, pantoprazole, omeprazole capsule, omeprazole MUPS tablet or placebo (P 相似文献   

Systematic review of proton pump inhibitors for the acute treatment of reflux oesophagitis

BACKGROUND: Esomeprazole is a new proton pump inhibitor, which has been compared to omeprazole for the treatment of reflux oesophagitis in clinical trials. AIM: To compare the effectiveness of esomeprazole with the recommended dose of proton pump inhibitors in the healing of reflux oesophagitis, using omeprazole as a common comparator. METHODS: Systematic review of randomized controlled trials. Extraction and re-analysis of data to provide 'intention-to-treat' results. Meta-analysis using a Fixed Effects model. RESULTS: A meta-analysis of healing rates of esomeprazole 40 mg compared to omeprazole 20 mg gave the following results: at 4 weeks (relative risk 1.14; 95% CI: 1.10, 1.18) and 8 weeks (RR 1.08; 95%CI: 1.05, 1.10). Other proton pump inhibitors compared to omeprazole 20 mg are as follows: lansoprazole 30 mg at 4 weeks (RR 1.02; 95%CI: 0.97, 1.08) and 8 weeks (RR 1.01; 95%CI: 0.97, 1.06); pantoprazole 40 mg at 4 weeks (RR 0.99; 95%CI: 0.91, 1.07) and 8 weeks (RR 0.98; 95%CI: 0.93, 1.04); rabeprazole 20 mg at 4 weeks (RR 1.00; 95%CI: 0.87, 1.14) and 8 weeks (RR 0.98; 95%CI: 0.91, 1.05). CONCLUSIONS: Esomeprazole has demonstrated higher healing rates than omeprazole at 4 and 8 weeks. Other proton pump inhibitors (lansoprazole, pantoprazole and rabeprazole) have not shown higher healing rates when compared with omeprazole.     

Acute pancreatitis associated with omeprazole

Since their introduction in the late 1980s, proton pump inhibitors (PPI) have demonstrated gastric acid suppression superior to that of histamine H2-receptor blockers. This class of drugs has improved the treatment of various acid-peptic disorders, including gastroesophageal reflux disease, peptic ulcer disease, and nonsteroidal anti-inflammatory drug-induced gastropathy. PPIs have minimal side effects and few significant drug interactions. They are generally considered safe for long-term treatment. We present a rare side effect, acute pancreatitis, occurring in a patient who was treated with the proton pump inhibitor omeprazole.     

Systematic review: proton pump inhibitors (PPIs) for the healing of reflux oesophagitis - a comparison of esomeprazole with other PPIs

BACKGROUND: No randomized controlled trial has compared all the licensed standard dose proton pump inhibitors in the healing of reflux oesophagitis. AIM: To compare the effectiveness of esomeprazole with licensed standard dose proton pump inhibitors for healing of reflux oesophagitis (i.e. lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg and rabeprazole 20 mg). METHODS: Systematic review of CENTRAL, BIOSIS, EMBASE and MEDLINE for randomized controlled trials in patients with reflux oesophagitis. Searching was completed in February 2005. Data on endoscopic healing rates at 4 and 8 weeks were extracted and re-analysed if not analysed by intention-to-treat. Meta-analysis was conducted using a fixed effects model. RESULTS: Of 133 papers identified in the literature search, six were of sufficient quality to be included in the analysis. No studies were identified comparing rabeprazole with esomeprazole. A meta-analysis of healing rates of esomeprazole 40 mg compared with standard dose proton pump inhibitors gave the following results: at 4 weeks [relative risk (RR) 0.92; 95% CI: 0.90, 0.94; P < 0.00001], and 8 weeks (RR 0.95; 95% CI: 0.94, 0.97; P < 0.00001). Publication bias did not have a significant impact on the results. The results were robust to changes in the inclusion/exclusion criteria and using a random effects model. CONCLUSION: Esomeprazole consistently demonstrates higher healing rates when compared with standard dose proton pump inhibitors.     

Comparison of lansoprazole with omeprazole on 24-hour pH, acid secretion and serum gastrin in healthy volunteers

Background: Lansoprazole and omeprazole are proton pump inhibitors which both strongly inhibit acid secretion, resulting in a significant increase in serum gastrin levels. However, no direct comparison of recommended doses (20 mg for omeprazole and 30 mg for lansoprazole) has been reported so far. Our aims were to compare the effects of omeprazole 20 mg/day and lansoprazole 30 mg/day on intragastric acidity and serum gastrin concentration in 12 healthy volunteers. Methods: The study was double-blind, randomized and placebo-controlled with a cross-over design. On the seventh day of each period, 24-hour intragastric pH was measured using a combined glass electrode placed in the proximal stomach. The last morning dose of each regimen was taken at the end of 24-hour pH monitoring; acid output and serum gastrin concentrations were then studied in the fasting state and after stimulation with pentagastrin (maximal acid output) and a meal (post-prandial gastrin response). Results: Compared to placebo, both drug regimens induced a sustained increase of 24-hour intragastric pH and significantly decreased basal and pentagastrin-stimulated acid secretion. Lansoprazole 30 mg was slightly more effective than omeprazole 20 mg in terms of time spent above pH 3 (P < 0.05). Accordingly post-prandial gastrin concentrations rose slightly more after lansoprazole than after omeprazole. All other differences were insignificant. Conclusions: Both lansoprazole 30 mg and omeprazole 20 mg induce potent and long-lasting acid inhibition, with few minor differences when the two proton pump inhibitors are used at standard doses.     

Review article: cytochrome P450 and the metabolism of proton pump inhibitors — emphasis on rabeprazole

The proton pump inhibitors rabeprazole, omeprazole, lansoprazole, and pantoprazole undergo an extensive hepatic biotransformation. In the liver, they are metabolized to varying degree by several cytochrome P450 (CYP) isoenzymes which are further categorized into subfamilies of related polymorphic gene products. The principal isoenzymes involved in the metabolism of proton pump inhibitors are CYP2C19 and CYP3A4. Of these two, minor mutations in CYP2C19 affect its activity in the liver and, in turn, the metabolic and pharmacokinetic profiles of the proton pump inhibitors. The metabolism of rabeprazole is less dependent on CYP2C19 and therefore is the least affected by this genetic polymorphism. Recent studies have brought to light the important role that this polymorphism plays in the therapeutic effectiveness of proton pump inhibitors during the treatment of acid-related diseases.     

Identification,Diagnosis, and Treatment of Acid-Related Diseases in the Elderly: Implications for Long-Term Care

Acid-related disorders such as peptic ulcer disease and gastroesophageal reflux disease occur frequently in the elderly and are associated with a high frequency of morbidity and mortality. The proton pump inhibitors lansoprazole and omeprazole produce faster rates of healing and greater symptomatic relief in patients with acid-related disorders than histamine₂-receptor antagonists, are well tolerated, and are associated with few adverse events. Compared with omeprazole, which interacts with diazepam, warfarin, and phenytoin, lansoprazole produces only a minor increase in theophylline clearance. Proton pump inhibitors in combination with antibiotic therapy can eradicate Helicobacter pylori, the main risk factor in the recurrence of peptic ulcer disease, obviating the need for maintenance therapy. Long-term acid suppression with proton pump inhibitors may be necessary to prevent the recurrence of gastroesophageal reflux disease. The safety and efficacy profile of these agents makes them ideal for the treatment of acid-related diseases in elderly patients. (Pharmacotherapy 1997;17(5);938–958)