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Lansoprazole
Selected AbstractsChanges of gastric histology in patients with erosive oesophagitis receiving long-term lansoprazole maintenance therapyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010M. M. Haber Aliment Pharmacol Ther 2010; 32: 83,96 Summary Background, Changes in gastric histology associated with long-term maintenance therapy with lansoprazole for erosive oesophagitis have not been well described. Aim, To evaluate the effect on gastric histology of long-term dose-titrated lansoprazole administered as maintenance therapy for up to 82 months in patients with erosive oesophagitis. Methods, Sequential gastric biopsy specimens were obtained for evaluation of histological changes and Helicobacter pylori infection status. Results, Active and chronic inflammation improved from baseline to final visit in a majority of patients receiving long-term therapy with lansoprazole, irrespective of baseline H. pylori infection status. Reductions in active inflammation in the gastric body and antrum were seen in 53% (17/32) and 67% (20/30) of H. pylori -positive patients, respectively, and in 88% (7/8) and 86% (12/14) of H. pylori -negative patients, respectively. Reductions in chronic inflammation in the gastric body and antrum were seen in 38% (12/32) and 47% (15/32) of H. pylori -positive patients, respectively, and in 58% (70/121) and 57% (68/120) of H. pylori -negative patients, respectively. No clinically meaningful increases in hyperplasia, dysplasia, neoplasia, intestinal metaplasia or atrophy were observed during the follow-up period. Conclusions, Lansoprazole administered as maintenance therapy for up to 6 years in patients with erosive oesophagitis demonstrated gastric mucosal safety and was well tolerated. [source] Clinical trial: lansoprazole 15 or 30 mg once daily vs. placebo for treatment of frequent nighttime heartburn in self-treating subjectsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009D. A. PEURA Summary Background, Frequent nighttime heartburn is common. Lansoprazole 15 mg is indicated for treatment of heartburn and other gastro-oesophageal reflux disease-related symptoms. Aim, To evaluate the efficacy and safety of lansoprazole in self-treating subjects with frequent nocturnal heartburn. Methods, A total of 864 subjects with heartburn on ,2 days/week over the past month were randomized to double-blind treatment with lansoprazole 15 or 30 mg or placebo each morning. Endpoints were percentage of nighttimes without heartburn (primary), percentage of 24-h days without heartburn and percentage of subjects without heartburn on day 1. Results, Mean percentage of nighttimes without heartburn was significantly greater with lansoprazole 15 mg (61.3%) or lansoprazole 30 mg (61.7%) vs. placebo (47.8%) over 14 days (P < 0.0001 vs. placebo for both doses). Percentage of 24-h days without heartburn and percentage of subjects without heartburn on day 1 were significantly greater with lansoprazole 15 or 30 mg vs. placebo. Conclusions, Both lansoprazole 15 and 30 mg were highly effective and well tolerated in reducing symptoms in subjects with frequent nighttime heartburn. The benefit of therapy on 24-h heartburn and nighttime heartburn on day 1 of treatment was also evident. Lansoprazole 15 mg is a suitable choice for management of frequent nighttime heartburn. [source] Lansoprazole, levofloxacin and amoxicillin triple therapy vs. quadruple therapy as second-line treatment of resistant Helicobacter pylori infectionALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2006W. M. WONG Summary Aim To test the efficacy of levofloxacin-based second-line therapy for resistant Helicobacter pylori infection. Methods One hundred and six patients who failed H. pylori eradication were randomized to receive (i) lansoprazole 30 mg, amoxicillin 1 g, levofloxacin 500 mg, all given twice daily for 7 days (LAL); or (ii) lansoprazole 30 mg twice daily, metronidazole 400 mg thrice daily, bismuth subcitrate 120 mg and tetracycline 500 mg four times daily for 7 days (quadruple). Post-treatment H. pylori status was determined by 13C-urea breath test. Results Intention-to-treat and per-protocol H. pylori eradication rates were 57/60% for the LAL group and 71/76% for the quadruple group respectively. Metronidazole, clarithromycin, amoxicillin and levofloxacin resistance were found in 76%, 71%, 0% and 18% of patients, respectively. Levofloxacin resistance led to treatment failure in the LAL group. For patients with dual resistance to metronidazole and clarithromycin, the eradication rates were 79% in the LAL group (levofloxacin-sensitive) and 65% in the quadruple group (P = 0.34). Conclusion Lansoprazole, amoxicillin plus levofloxacin second-line therapy is comparable with quadruple therapy in efficacy. Subjects, especially those with dual resistance to metronidazole and clarithromycin, may consider levofloxacin-based therapy for levofloxacin-sensitive strains. [source] Effect of concomitant dosing of famotidine with lansoprazole on gastric acid secretion in relation to CYP2C19 genotype statusALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2005T. FURUTA Background :,Famotidine increases Helicobacter pylori -eradication rates by a triple lansoprazole/amoxicillin/clarithromycin therapy in patients with the rapid extensive metabolizer genotype of CYP2C19. Aim :,To determine the effect of famotidine on the gastric acid inhibition by lansoprazole in relation to CYP2C19 genotypes. Methods :,Twenty healthy volunteers with different CYP2C19 genotypes , consisting of six rapid extensive metabolizers, nine intermediate metabolizers and five poor metabolizers , underwent three 7-day courses with placebo, lansoprazole 30 mg twice daily, and lansoprazole 30 mg twice plus famotidine 20 mg twice daily. Lansoprazole was dosed after breakfast and dinner. Famotidine was dosed after lunch and at bedtime. Intragastric pH monitoring was performed for 24 h on day 7 of each course. Results :,With placebo, no difference was observed in intragastric pH profiles among the three CYP2C19 genotype groups. With lansoprazole 30 mg twice daily, the median of 24-h intragastric pH in poor metabolizers (6.1) was significantly higher than those of rapid extensive metabolizers (4.5) and intermediate metabolizers (5.0), respectively (P = 0.0176 and 0.0388), whereas with lansoprazole 30 mg twice and famotidine 20 mg twice daily, the medians were 5.4, 5.7, and 6.1, respectively (not significant). Conclusion :,Acid inhibition by lansoprazole was influenced by CYP2C19 genotype status. This influence was offset by the concomitant use of famotidine. [source] Lansoprazole in children: pharmacokinetics and efficacy in reflux oesophagitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2001C. Faure Background: Data on the proton pump inhibitor lansoprazole in paediatric patients are limited. Aim: To investigate the pharmacokinetics, optimal dosage and efficacy of lansoprazole in paediatric patients. Methods: A 24-h gastric pH recording and a pharmacokinetic study were performed after 7 days of lansoprazole, 17 mg/m2, in 23 patients with reflux oesophagitis (median age, 3.5 years). Response was defined as pH > 3 for > 65% of the recording. The dosage was doubled in non-responders. Patients with no response on day 14 were excluded. Responders underwent endoscopy after 4 weeks on the response-inducing dosage; abnormal findings led to a repeat endoscopy after four additional weeks. Results: Nine patients responded to 17 mg/m2 and six to 30.3 mg/m2. On day 7, time with pH > 3 was significantly correlated with the area under the plasma concentration,time curve (P=0.003). The area under the plasma concentration,time curve was significantly greater in the nine responders to 17 mg/m2 than in the 14 other patients. Pharmacokinetic parameters were similar in responders and non-responders to the higher dose. After 4 weeks, oesophagitis was healed in 80% of responders. Adverse events occurred in three patients and required treatment discontinuation in one. Conclusions: Lansoprazole is effective and safe in children. The optimal starting dosage is 30 mg/m2 or 1.4 mg/kg. [source] Eradication of Helicobacter pylori increases platelet count in patients with idiopathic thrombocytopenic purpura in JapanEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2005T. Inaba Abstract Background, The effect of Helicobacter pylori eradication on the platelet count in patients with thrombocytopenic purpura is controversial. In this multicentre study, we prospectively assessed the effect of H. pylori eradication therapy in idiopathic thrombocytopenic purpura patients. Materials and methods, Thirty-five consecutive patients with chronic idiopathic thrombocytopenic purpura (11 males and 24 females, a median age of 57) were assessed for H. pylori infection by use of a urea breath test. All patients received 1-week triple therapy (amoxicillin, clarithromycin, and lansoprazole) to eradicate H. pylori. At 6 months, idiopathic thrombocytopenic purpura patients with a platelet count recovery of greater than 100 × 109 L,1 were defined as idiopathic thrombocytopenic purpura responders. Results,Helicobacter pylori infection was observed in 25 (71%) of the 35 patients. All infected patients were cured. Eleven patients were identified as idiopathic thrombocytopenic purpura responders; 24 were considered nonresponders. Platelet counts improved by more than 100 × 109 L,1 in 11 (44%) of the 25 patients cured of H. pylori infection, while none of the 10 patients H. pylori -negative patients experienced the same improvement (P = 0·015). Univariate analysis showed that H. pylori infection and its eradication were significant factors associated with platelet recovery (P = 0·015). Conclusions,Helicobacter pylori infection played a role in the pathogenesis of idiopathic thrombocytopenic purpura in approximately 30% of all patients assessed and 45% of the patients with H. pylori infection. Eradication of H. pylori in idiopathic thrombocytopenic purpura patients led to improved disease activity. [source] Helicobacter pylori Eradication Therapy May Facilitate Gastric Ulcer Healing After Endoscopic Mucosal Resection: A Prospective Randomized StudyHELICOBACTER, Issue 6 2008Jae Hee Cheon Abstract Background and Aim:, It remains unclear whether Helicobacter pylori eradication therapy affects the healing rate of iatrogenic ulcers following endoscopic mucosal resection (EMR) for gastric tumors. The aim of our study was to prospectively evaluate the effect of H. pylori eradication therapy on gastric ulcer healing after EMR. Methods:, After EMR, patients were randomly assigned to either the H. pylori eradication group (Hp group) (lansoprazole 30 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, twice a day for 7 days) or the noneradication group (proton pump inhibitor, PPI group) (lansoprazole 30 mg, twice a day for 7 days). Four weeks after EMR, the ulcer stages and size were compared between the two groups. Moreover, ulcer-related symptoms, bleeding rates, adverse effects, and drug compliance were compared. Results:, A total of 64 patients were enrolled. Of these, 17 patients were excluded from the study. The two groups were comparable in terms of baseline clinicopathologic characteristics. Four weeks after EMR, the two groups did not differ with respect to ulcer stage (p = .475) or ulcer-related symptoms (p = .399). However, the ulcer reduction ratio was significantly higher in the Hp group (0.028 ± 0.024 vs. 0.065 ± 0.055, p < .05). No differences were observed between the two groups with regard to drug compliance, adverse drug event rates, or bleeding rates. Conclusions:, Our results suggest that H. pylori eradication therapy might improve the ulcer healing rate after EMR. [source] Recent Use of Proton Pump Inhibitor-Based Triple Therapies for the Eradication of H. pylori: A Broad Data ReviewHELICOBACTER, Issue 2 2003Hans-Joachim Ulmer abstract Introduction. For the eradication of Helicobacter pylori a 1-week triple therapy combining proton pump inhibitors with two antibiotics has been recommended as a gold standard therapy. However, a recent broad data review on the efficacy of the different regimens is missing. Therefore, the aim of this study was to systematically review the recent literature. Methods. We undertook a broad data review of the efficacy of nine different 7-day triple therapies consisting of a proton pump inhibitor (lansoprazole, pantoprazole, omeprazole) in its standard dosage and two antibiotics. Relevant original papers on H. pylori eradication in adults, published in English or German between 1995 and 2000, were identified from MEDLINE searches. Studies were reviewed and selected according to predefined criteria. Results. Our predefined criteria were fulfilled by 79 full paper articles including 112 study arms with 8383 patients on intention-to-treat, or 6787 patients on per-protocol basis, respectively. The mean eradication rates unweighted or weighted by the number of patients in the study arm vary from 71.9% to 83.8% for intention-to-treat analysis and from 78.5% to 91.2% for per-protocol analysis. Conclusions. All nine PPI based triple therapy regimens are very effective in H. pylori eradication. The current literature review underlines that the use of either lansoprazole, omeprazole, or pantoprazole combined with two antibiotics yield similar high eradication rates. [source] Impact of Furazolidone-Based Quadruple Therapy for Eradication of Helicobacter pylori after Previous Treatment FailuresHELICOBACTER, Issue 4 2002G. Treiber Abstract Background. One week of quadruple therapy including metronidazole is recommended for Helicobacter pylori treatment failures after first line therapy regardless of resistance status. This study investigated whether a quadruple regimen containing furazolidone could be effective as a third-line (salvage) therapy. Methods. All patients with previous H. pylori treatment failure after a clarithromycin-metronidazole ± amoxicillin combination plus acid suppression were given lansoprazole 30 mg twice a day (bid), tripotassiumdicitratobismuthate 240 mg bid, tetracycline 1 g bid, metronidazole 400 mg (PPI-B-T-M) three times a day (tid) for 1 week. In the case of treatment failure with this second-line therapy, the same regimen was applied for 1 week except for using furazolidone 200 mg bid (PPI-B-T-F) instead of metronidazole (sequential study design). Results. Eighteen consecutive patients were treated with PPI-B-T-M. Eleven of those 18 remained H. pylori positive (38.9% cured). Pretherapeutic metronidazole resistance was associated with a lower probability of eradication success (10% vs. 75%, p= .04). Ten of these 11 patients agreed to be retreated by PPI-B-T-F. Final cure of H. pylori with PPI-B-T-F was achieved in 9/10 patients (90%) nonresponsive to PPI-B-T-M. Conclusions. In the presence of metronidazole resistance, PPI-B-T-M as a recommended second-line therapy by the Maastricht consensus conference achieved unacceptable low cure rates in our metronidazole pretreated population. In this population, metronidazole based second-line quadruple therapy may be best suited in case of a metronidazole-free first line-regimen (e.g. PPI-clarithromycin-amoxicillin) or a low prevalence of metronidazole resistance. Furazolidone in the PPI-B-T-F combination does not have a cross-resistance potential to metronidazole and is a promising salvage option after a failed PPI-B-T-M regimen. [source] Helicobacter pylori and Early Duodenal Ulcer Status Post-Treatment: a ReviewHELICOBACTER, Issue 2 2001Joette M. Meyer Abstract Background. Data submitted to the FDA were reviewed to analyze the relationship between Helicobacter pylori infection and the incidence of early duodenal ulcers, within 6 weeks, following treatment. Materials and Methods. Retrospective analyzes were performed on data from three H. pylori development programs submitted to the FDA: ranitidine-bismuth-citrate (RBC), lansoprazole (L) and omeprazole (O). Efficacy assessments for the RBC, L and O programs were made at end of a 4-week treatment period, 4,6 weeks following the end of a 14-day treatment period, and 4 weeks following the end of a 4-week treatment period, respectively. Results. Overall, there was a 15%, 21% and 23% decrease in the number of patients in the RBC, L and O programs, respectively, with ulcers among H. pylori cleared/eradicated patients post-treatment compared with patients with persistent infection. Among patients who did not have cleared/eradicated H. pylori in the RBC and O programs, where antisecretory agents were continued beyond the antimicrobial treatment period, the number of ulcers was lower in the antisecretory plus antimicrobial subgroups compared with the antimicrobial alone subgroups (37% vs. 46% for RBC and 33% vs. 42% for O). Among patients with cleared/eradicated H. pylori, the number of patients with ulcers in the antimicrobial alone subgroups and antisecretory plus antimicrobial subgroups were similar within each program. Antimicrobials alone had significantly lower rates of ulcers among patients with cleared/eradicated H. pylori as compared with patients without clearance/eradication. Conclusions. The early incidence of duodenal ulcers is significantly decreased in patients with H. pylori clearance/eradication. [source] Conformational analysis: A new approach by means of chemometricsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 2 2002Aline Thaís Bruni Abstract In conformational analysis, the systematic search method completely maps the space but suffers from the combinatorial explosion problem because the number of conformations increases exponentially with the number of free rotation angles. This study introduces a new methodology of conformational analysis that controls the combinatorial explosion. It is based on a dimensional reduction of the system through the use of principal component analysis. The results are exactly the same as those obtained for the complete search but, in this case, the number of conformations increases only quadratically with the number of free rotation angles. The method is applied to a series of three drugs: omeprazole, pantoprazole, lansoprazole,benzimidazoles that suppress gastric-acid secretion by means of H+, K+ -ATPase enzyme inhibition. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 222,236, 2002 [source] Influence of lansoprazole, famotidine, roxatidine and rebamipide administration on the urea breath test for the diagnosis of Helicobacter pylori infectionJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2003KYOICHI ADACHI Abstract Background and Aim:, The sensitivity of the urea breath test (UBT) has been reported to be influenced by the administration of omeprazole, lansoprazole and ranitidine. However, it is unclear whether other H2 receptor antagonists (H2RA), except ranitidine, and rebamipide, a mucosal protective agent, affect UBT sensitivity. The aim of this study is to clarify the effects of lansoprazole, famotidine, roxatidine and rebamipide administration on UBT sensitivity. Methods:, Subjects comprised 30 volunteers with Helicobacter pylori infection. All subjects were examined by the 13C-UBT on four occasions: (i) without medication (control); (ii) after the administration of 30 mg lansoprazole (u.i.d) for 14 days; (iii) after the administration of 100 mg rebamipide (t.i.d) for 14 days; and (iv) after the administration of 20 mg famotidine or 75 mg roxatidine (b.i.d) for 14 days. In the H2RA study, individuals were randomized into two groups of 15 subjects and were administered either famotidine or roxatidine. Results:, Five of the 30 cases administered lansoprazole and one of the 15 cases given roxatidine gave a false-negative UBT result. No negative UBT results were observed in patients administered famotidine or rebamipide. Conclusion:, Patients showing negative UBT results during the administration of proton pump inhibitors and H2RA should be re-examined after the cessation of these drugs to confirm the true negativity of H. pylori infection. [source] Influence of Helicobacter pylori infection and cetraxate on gastric mucosal blood flow during healing of endoscopic mucosal resection-induced ulcersJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2001Kyoichi Adachi Abstract Background and Aim: Helicobacter pylori (H. pylori) infection is known to affect the gastric microcirculation, and cetraxate is reported to accelerate gastric ulcer healing, possibly by augmenting gastric mucosal blood flow (MBF). The aim of this study is to clarify the effect of H. pylori infection and cetraxate on MBF during gastric ulcer healing. Methods: Forty-two patients who had undergone endoscopic mucosal resection (EMR) were studied. Mucosal blood flow was measured by the use of a laser Doppler flowmeter in the surrounding mucosa and at the ulcer margin, before, 1 day, 1 week and 4 weeks after EMR. Helicobacter pylori infection was confirmed by the use of bacterial culture and histology. After EMR, patients were randomly assigned to receive 30 mg lansoprazole (u.i.d; L-regimen) or 30 mg lansoprazole (u.i.d.) with 200 mg cetraxate (q.i.d; LC-regimen) for 4 weeks. Results: The MBF ratio (MBF at ulcer margin/MBF in surrounding mucosa) 1 week after EMR was significantly lower than that before or 4 weeks after EMR only in H. pylori -positive patients treated with the L-regimen. No such decrease in MBF was observed after 1 week in H. pylori -positive patients treated with the LC-regimen or in H. pylori -negative patients. Conclusion: A transient decrease in MBF was detected at the ulcer margin during healing of EMR-induced ulcers in H. pylori -infected patients. Cetraxate seemed to prevent this decrease in MBF. [source] A decade-long sour-taste sensation successfully treated with a proton-pump inhibitorJOURNAL OF ORAL REHABILITATION, Issue 10 2005N. MANTANI summary We report a case study of a 54-year-old Japanese woman who persistently suffered from a sour-taste sensation in her mouth for 10 years, and was treated with a proton-pump inhibitor (PPI). She found sour-tasting meals irritable, and after eating such meals the sour-taste sensation worsened. She also complained of eructation and regurgitation. Upper gastrointestinal (GI) endoscopy showed duodenal erosion, superficial gastritis, and erosive oesophagitis. After 2 weeks of PPI therapy (lansoprazole, 30 mg day,1) the sour taste subjectively decreased to 70%, and after 6 weeks the symptoms disappeared. In addition to increased sensitivity of the mouth, gastro-oesophageal reflux might have created her obstinate sour-taste sensations. It is suggested that in such cases PPI therapy should be attempted. [source] Gastroprotective activity of ferruginol in mice and rats: effects on gastric secretion, endogenous prostaglandins and non-protein sulfhydrylsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2008Carlos Areche The gastroprotective mechanism of the natural diterpene ferruginol was assessed in mice and rats. The involvement of gastric prostaglandins (PGE2), reduced glutathione, nitric oxide or capsaicin receptors was evaluated in mice either treated or untreated with indometacin, N-ethylmaleimide (NEM), N-nitro-L-arginine methyl ester (L-NAME) or ruthenium red, respectively, and then orally treated with ferruginol or vehicle. Gastric lesions were induced by oral administration of ethanol. The effects of ferruginol on the parameters of gastric secretion were assessed in pylorus-ligated rats. Gastric PGE2 content was determined in rats treated with ferruginol and/or indometacin. The reduction of gastric glutathione (GSH) content was determined in rats treated with ethanol after oral administration of ferruginol, lansoprazole or vehicle. Finally, the acute oral toxicity was assessed in mice. Indometacin reversed the gastroprotective effect of ferruginol (25 mg kg,1) but not NEM, ruthenium red or L-NAME. The diterpene (25 mg kg,1) increased the gastric juice volume and its pH value, and reduced the titrable acidity but was devoid of effect on the gastric mucus content. Ferruginol (25, 50 mg kg,1) increased gastric PGE2 content in a dose-dependent manner and prevented the reduction in GSH observed due to ethanol-induced gastric lesions in rats. Single oral doses up to 3 g kg,1 ferruginol did not elicit mortality or acute toxic effects in mice. Our results showed that ferruginol acted as a gastroprotective agent stimulating the gastric PGE2 synthesis, reducing the gastric acid output and improving the antioxidant capacity of the gastric mucosa by maintaining the GSH levels. [source] Gastroprotective and cytotoxic effect of semisynthetic ferruginol derivativesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2007Carlos Areche The gastroprotective abietane diterpene ferruginol has been shown to present high cytotoxicity. In order to obtain active compounds with less cytotoxicity, 18 semisynthetic ferruginol derivatives and totarol were assessed for their gastroprotective effects in the HCl/ethanol-induced gastric lesion model in mice, as well as for cytotoxicity in human gastric epithelial cells (AGS) and human lung fibroblasts (MRC-5). At 20 mg kg,1, the greatest gastroprotective effects were provided by abieta-8,11,13-triene (1), abieta-8,11,13-trien-12-yl-2-chloropropanoate (8), abieta-8,11,13-trien-12-yl propenoate (9), 12-(2,3,4,6-tetra- O -acetyl-,-D-glucopyranosyloxy)-abieta-8,11,13-triene (17) and 12-(,-D-galactopyranosyloxy)-abieta-8,11,13-triene (18), all of which were as active as the reference drug lansoprazole at 20 mg kg,1, reducing gastric lesions by 69, 76, 67, 72 and 61%, respectively. No relation was observed between lipophilicity and the gastroprotective effect. Compounds that showed the greatest cytotoxicity towards AGS cells were ferruginol (2), the corresponding formate (5), acetate (6), propionate (7), 8, 9, 12-(,-D-glucopyranosyloxy)-abieta-8,11,13-triene (16), 18 and totarol (20) (IC50 18,44 ,M). Ferruginol and compounds 5,9, 16, 18 and 20 were the most toxic compounds against fibroblasts (IC50 19,56 ,M), with a correlation to AGS cells. The derivative 19 was much more active against AGS cells than towards fibroblasts. The best activity/cytotoxicity ratio was found for compound 17, with a lesion index comparable with lansoprazole at 20 mg kg,1 and cytotoxicity >1000 ,M towards MRC-5 and AGS cells, respectively. In conclusion, some derivatives showed a better gastroprotective effect/cytotoxicity ratio than the parent compound ferruginol. A total of 13 new compounds are reported here for the first time. [source] Effect of lansoprazole and rabeprazole on tacrolimus pharmacokinetics in healthy volunteers with CYP2C19 mutationsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2004Fumio Itagaki The aim of this study was to investigate the effects of the proton pump inhibitors (PPIs), lansoprazole and rabeprazole, on tacrolimus pharmacokinetics in healthy volunteers with mutations in the cytochrome P450 (CYP) 2C19 gene (CYP2C19). An open-label crossover study was performed with 19 healthy subjects. Tacrolimus (2 mg) was administered orally with and without lansoprazole (30 mg per day for 4 days) or rabeprazole (10 mg per day for 4 days). Blood concentrations of tacrolimus were determined before and 1, 2, 4 and 8 h after dosing. Genotyping for CYP2C19 was conducted by a polymerase chain reaction-restriction fragment length polymorphism method. Coadministration of lansoprazole significantly decreased the oral tacrolimus clearance, resulting in an increase in the area under the blood concentration-time curve (AUC0,8) (control vs with lansoprazole: 29.7 ± 3.5 vs 44.1 ± 5.0 ng h mL,1, P<0.05). Large individual variation was observed in the effects of lansorazole on tacrolimus AUC0,8 owing to CYP2C19 genotype status. The percent change for tacrolimus AUC0,8 in subjects with and without CYP2C19 mutant alleles was 81% and 29%, respectively. Coadministration of rabeprazole also increased the mean AUC0,8 of tacrolimus, but the difference was not statistically significant. These observations suggest that drug interaction between tacrolimus and lansoprazole occurs in subjects with higher lansoprazole blood concentrations corresponding to CYP2C19 genetic status. In contrast, rabeprazole has minimal effect on tacrolimus pharmacokinetics regardless of CYP2C19 genotype status. [source] Semipreparative chiral supercritical fluid chromatography in the fractionation of lansoprazole and two related antiulcer drugs enantiomersJOURNAL OF SEPARATION SCIENCE, JSS, Issue 8 2008Laura Toribio Abstract The semipreparative chiral separation of lansoprazole and two related compounds (pantoprazole and rabeprazole) using supercritical fluid chromatography (SFC) is presented in this work. Different loads were evaluated in order to obtain high enantiomeric purities and production rates. The volumes injected were 1, 2 and 4 mL. The concentrations of the racemic mixtures were 3 and 6 g/L for lansoprazole and 1.5 g/L for pantoprazole and rabeprazole. In all the cases, the recoveries, for a purity higher than 99.9%, were better for the second eluted enantiomer than for the first one. This fact conditioned the production rate of the first eluted enantiomer that, considering a fixed purity, was always lower than that obtained for the other one. In the case of lansoprazole it was possible to obtain 0.025 and 0.090 mg/min of the first and second eluted enantiomer, respectively, with an enantiomeric purity of 99.9%. For rabeprazole enantiomers 0.037 and 0.062 mg/min, and in the case of pantoprazole the results were better (0.062 and 0.122 mg/min) due to the higher resolution. [source] Dilated intercellular space in chronic laryngitis and gastro-oesophageal reflux disease: at baseline and post-lansoprazole therapyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2010M. F. Vaezi Aliment Pharmacol Ther 2010; 32: 916,924 Summary Background, Dilation of intercellular spaces is reported to be an early morphological marker in gastro-oesophageal reflux. It remains unknown if this marker is useful in diagnosing reflux-related chronic laryngitis. Aim, To determine histopathology and electron microscopic changes in oesophageal and laryngeal epithelium in chronic laryngitis. Methods, In this prospective blinded study, we enrolled 53 participants: 15 controls, 20 patients with GERD and 18 patients with chronic laryngitis. The latter two groups were subsequently treated with lansoprazole 30 mg bid for 12-weeks. Baseline and postacid suppressive therapy biopsies were obtained from distal oesophagus and laryngeal postcricoid areas. Biopsy specimens were evaluated for histopathology and dilated intercellular space changes. Results, There was no significant increase in oesophageal or laryngeal epithelium intercellular spaces among GERD or laryngitis patients compared with controls at baseline or postacid suppressive therapy. Only patients with GERD had significantly (P = 0.03) higher proportion of moderate-to-severe oesophageal spongiosis and basal cell hyperplasia, which normalized postacid suppressive therapy. Conclusions, There was no increase in the width of intercellular spaces in the oesophagus or larynx in GERD or chronic laryngitis at baseline or postacid suppressive therapy. Our findings question the uniform presence of dilated intercellular space in patients with GERD. [source] Clinical trial: chest pain caused by presumed gastro-oesophageal reflux in coronary artery disease , controlled study of lansoprazole vs. placeboALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010V. Talwar Aliment Pharmacol Ther 2010; 32: 191,199 Summary Background, Gastro-oesophageal reflux (GER) and coronary artery disease commonly co-exist. Coronary artery disease patients may mistake GER-induced pain for cardiac pain or GER might provoke angina. Aim, To investigate if GER might contribute to nocturnal/rest chest pain among coronary artery disease patients. Methods, Double-blind placebo-controlled crossover study investigating effect of lansoprazole on chest pain; 125 patients with angiographically proven coronary artery disease enrolled with at least one weekly episode of nocturnal/rest pain, randomized to lansoprazole 30 mg daily or placebo with crossover after 4 weeks. Symptoms recorded and QOL assessed by Nottingham Health Profile Questionnaire; ST segment depression episodes counted from 24 h electrocardiographic monitoring in final week of both periods. Statistical analysis: ANCOVA with period and carryover analysis. Results, In all, 108 patients completed the study. There was a modest increase in pain-free days on lansoprazole vs. placebo (P < 0.02), with fewer days with pain at rest (P < 0.05) and at night (P < 0.009) on lansoprazole vs. placebo, but no significant differences in ST segment depression episodes (P = 0.64). There was a trend for reduction in the ,physical pain' QOL domain. Conclusions, Among coronary artery disease patients, lansoprazole modestly increases pain-free days and reduces rest/nocturnal pain. As lansoprazole did not affect ST segments, this may be by suppression of GER-provoked pain misinterpreted as angina, rather than acid-provoked ischaemia. [source] Clinical trial: gastric acid suppression in Hispanic adults with symptomatic gastro-oesophageal reflux disease , comparator study of esomeprazole, lansoprazole and pantoprazoleALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010D. Morgan Aliment Pharmacol Ther 2010; 32: 200,208 Summary Background, Hispanic-Americans are a rapidly growing population in the United States, yet gastro-oesophageal reflux disease (GERD) is not well studied in this population. Aim, To compare the efficacy of esomeprazole, lansoprazole and pantoprazole in suppressing gastric acid, including the area of the ,acid pocket,' in Hispanics with GERD. Methods, In this open-label, 3-way crossover study, 83 Hispanics with symptomatic GERD were randomized to 1 of 6 possible treatment sequences of three 5,7-day dosing periods with esomeprazole 40 mg, lansoprazole 30 mg and pantoprazole 40 mg daily separated by 10,17-day washout periods. Intragastric pH was measured for 24 h using dual probes with a distal and proximal (area of the ,acid pocket') electrode. Results, Esomeprazole suppressed intragastric acid (pH >4.0) significantly longer over 24 h (primary end point) compared with lansoprazole and pantoprazole (P < 0.0001), and proximal gastric acid (pH >4.0) significantly longer over 24 h compared with lansoprazole (P < 0.05) and pantoprazole (P < 0.0001). Conclusions, Esomeprazole was more effective than lansoprazole and pantoprazole in suppressing gastric acidity at both intragastric distal and proximal (area of the acid pocket) sites in Hispanics with GERD. Future studies are warranted to understand better the role of the acid pocket in GERD (Clinical trial numbers: D9612L00106; ClinicalTrials.gov: NCT00410592). [source] Changes of gastric histology in patients with erosive oesophagitis receiving long-term lansoprazole maintenance therapyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010M. M. Haber Aliment Pharmacol Ther 2010; 32: 83,96 Summary Background, Changes in gastric histology associated with long-term maintenance therapy with lansoprazole for erosive oesophagitis have not been well described. Aim, To evaluate the effect on gastric histology of long-term dose-titrated lansoprazole administered as maintenance therapy for up to 82 months in patients with erosive oesophagitis. Methods, Sequential gastric biopsy specimens were obtained for evaluation of histological changes and Helicobacter pylori infection status. Results, Active and chronic inflammation improved from baseline to final visit in a majority of patients receiving long-term therapy with lansoprazole, irrespective of baseline H. pylori infection status. Reductions in active inflammation in the gastric body and antrum were seen in 53% (17/32) and 67% (20/30) of H. pylori -positive patients, respectively, and in 88% (7/8) and 86% (12/14) of H. pylori -negative patients, respectively. Reductions in chronic inflammation in the gastric body and antrum were seen in 38% (12/32) and 47% (15/32) of H. pylori -positive patients, respectively, and in 58% (70/121) and 57% (68/120) of H. pylori -negative patients, respectively. No clinically meaningful increases in hyperplasia, dysplasia, neoplasia, intestinal metaplasia or atrophy were observed during the follow-up period. Conclusions, Lansoprazole administered as maintenance therapy for up to 6 years in patients with erosive oesophagitis demonstrated gastric mucosal safety and was well tolerated. [source] Omeprazole-Mg 20.6 mg is superior to lansoprazole 15 mg for control of gastric acid: a comparison of over-the-counter doses of proton pump inhibitorsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010P. B. MINER JR Aliment Pharmacol Ther,31, 846,851 Summary Background, Over-the-counter (OTC) proton pump inhibitors (PPIs) relieve heartburn by decreasing the production of gastric acid, but may not do so with equal effectiveness. It is important for healthcare professionals to compare the ability of OTC PPIs to control gastric acid when recommending them for patients with frequent heartburn. Aim, To compare the effects of omeprazole-Mg 20.6 mg and lansoprazole 15 mg (OTC doses in the US) on 24-h steady state gastric acid suppression. Methods, This single-centre, randomized, double-blind clinical study compared the steady-state gastric acid control of omeprazole-Mg 20.6 mg vs. lansoprazole 15 mg, dosed before breakfast. Volunteers were enrolled in a 3-period, cross-over design (ABB, BAA) with 24-h gastric pH monitoring on dosing day 5. The primary efficacy variable was the percentage time intragastric pH was >4.0 over 24 h on day 5 of dosing. Results, Forty subjects were enrolled; all completed the study. The mean (SE) percentage time pH was >4.0 was 45.7% (3.45%) for omeprazole-Mg 20.6 mg and 36.8% (3.45%) for lansoprazole 15 mg, an absolute difference of 8.9% (P < 0.0001), and a relative difference of 24.2%. Both drugs were well tolerated. Conclusion, Omeprazole-Mg 20.6 mg provided a statistically significantly (P < 0.0001) greater acid control than lansoprazole 15 mg. [source] Safety profile of dexlansoprazole MR, a proton pump inhibitor with a novel dual delayed release formulation: global clinical trial experienceALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2009D. A. PEURA Summary Background, Dexlansoprazole MR is a dual delayed release formulation of dexlansoprazole, an enantiomer of lansoprazole. Aim, To assess safety of dexlansoprazole MR in phase 3 clinical trials. Methods, Data from 4270 patients receiving dexlansoprazole MR 30 mg (n = 455), 60 mg (n = 2311) or 90 mg (n = 1864); lansoprazole 30 mg (n = 1363); or placebo (n = 896) in six randomized controlled trials and a 12-month safety study were pooled. Safety was assessed via adverse events, vital signs, electrocardiograms, clinical laboratory results and gastric biopsies. Adverse events were summarized per 100 patient-months of exposure to account for imbalances in study drug exposure. Results, The number of patients with ,1 treatment-emergent adverse event per 100 patient-months was higher in placebo (24.49) and lansoprazole (21.06) groups than in any dexlansoprazole MR (15.64,18.75) group. Fewer patients receiving dexlansoprazole MR discontinued therapy because of an adverse event (P , 0.05 vs. placebo). Seven patients died of events considered unrelated to study drug. Mean serum gastrin rose in all groups except placebo; increases were not dose-related. No clinically concerning trends were seen in gastric biopsy results. Endocrine cell hyperplasia, dysplasia and neoplasia were not observed. Conclusion, Dexlansoprazole MR 30,90 mg has a safety profile comparable to that of lansoprazole. [source] Clinical trial: efficacy and safety of dexlansoprazole MR 60 and 90 mg in healed erosive oesophagitis , maintenance of healing and symptom reliefALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2009C. W. HOWDEN Summary Background, Dexlansoprazole MR, a modified-release formulation of dexlansoprazole, an enantiomer of lansoprazole, effectively heals erosive oesophagitis. Aim, To assess dexlansoprazole MR in maintaining healed erosive oesophagitis. Methods, Patients (n = 451) with erosive oesophagitis healed in either of two dexlansoprazole MR healing trials randomly received dexlansoprazole MR 60 or 90 mg or placebo once daily in this double-blind trial. The percentage of patients who maintained healing at month 6 was analysed using life table and crude rate methods. Secondary endpoints were percentages of nights and of 24-h days without heartburn based on daily diaries. Results, Dexlansoprazole MR 60 and 90 mg were superior to placebo for maintaining healing (P < 0.0025). Maintenance rates were 87% and 82% for the 60 and 90 mg doses, respectively, vs. 26% for placebo (life table), and 66% and 65% vs. 14%, respectively (crude rate). Both doses were superior to placebo for the percentage of 24-h heartburn-free days (60 mg, 96%; 90 mg, 94%; placebo, 19%) and nights (98%, 97%, and 50%, respectively). Diarrhoea, flatulence, gastritis (symptoms) and abdominal pain occurred more frequently with dexlansoprazole MR than placebo, but were not dose-related. Conclusion, Dexlansoprazole MR effectively maintained healed erosive oesophagitis and symptom relief compared with placebo, and was well tolerated. [source] Systematic review: standard- and double-dose proton pump inhibitors for the healing of severe erosive oesophagitis , a mixed treatment comparison of randomized controlled trialsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009S. J. EDWARDS Summary Background, No randomized controlled trial (RCT) has compared all European-licensed standard- and double-dose PPIs for the healing of severe erosive oesophagitis. Aim, To compare the effectiveness of licensed doses of PPIs for healing severe erosive oesophagitis (i.e. esomeprazole 40 mg, lansoprazole 30 mg, omeprazole 20 mg and 40 mg, pantoprazole 40 mg and rabeprazole 20 mg). Methods, Systematic review of CENTRAL, EMBASE and MEDLINE for RCTs in patients with erosive oesophagitis (completed October 2008). Endoscopically verified healing rates at 4 and 8 weeks were extracted and re-calculated if not analysed by intention-to-treat. A mixed treatment comparison was used to combine direct treatment comparisons with indirect trial evidence while maintaining randomization. Odds ratios (OR) are reported compared to omeprazole 20 mg. Results, A total of 3021 papers were identified in the literature search; 12 were of sufficient quality to be included in the analysis. Insufficient data were available to included rabeprazole. Esomeprazole 40 mg was found to provide significantly higher healing rates at 4 weeks [OR 1.84, 95% Credible Interval (95% CrI): 1.50 to 2.22] and 8 weeks (OR 1.91, 95% CrI: 1.13 to 2.88). No other PPI investigated had significantly higher healing rates than omeprazole 20 mg. Conclusion, Esomeprazole 40 mg consistently demonstrates higher healing rates compared with licensed standard- and double-dose PPIs. [source] Clinical trial: lansoprazole 15 or 30 mg once daily vs. placebo for treatment of frequent nighttime heartburn in self-treating subjectsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009D. A. PEURA Summary Background, Frequent nighttime heartburn is common. Lansoprazole 15 mg is indicated for treatment of heartburn and other gastro-oesophageal reflux disease-related symptoms. Aim, To evaluate the efficacy and safety of lansoprazole in self-treating subjects with frequent nocturnal heartburn. Methods, A total of 864 subjects with heartburn on ,2 days/week over the past month were randomized to double-blind treatment with lansoprazole 15 or 30 mg or placebo each morning. Endpoints were percentage of nighttimes without heartburn (primary), percentage of 24-h days without heartburn and percentage of subjects without heartburn on day 1. Results, Mean percentage of nighttimes without heartburn was significantly greater with lansoprazole 15 mg (61.3%) or lansoprazole 30 mg (61.7%) vs. placebo (47.8%) over 14 days (P < 0.0001 vs. placebo for both doses). Percentage of 24-h days without heartburn and percentage of subjects without heartburn on day 1 were significantly greater with lansoprazole 15 or 30 mg vs. placebo. Conclusions, Both lansoprazole 15 and 30 mg were highly effective and well tolerated in reducing symptoms in subjects with frequent nighttime heartburn. The benefit of therapy on 24-h heartburn and nighttime heartburn on day 1 of treatment was also evident. Lansoprazole 15 mg is a suitable choice for management of frequent nighttime heartburn. [source] [13C]-pantoprazole breath test to predict CYP2C19 phenotype and efficacy of a proton pump inhibitor, lansoprazoleALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009T. FURUTA Summary Background,13CO2 is produced on metabolism of 13C-labelled-pantoprazole ([13C]-pantoprazole) by CYP2C19. Aim, To investigate whether the [13C]-pantoprazole breath test can predict CYP2C19 status and efficacy of proton pump inhibitors (PPIs) in Japanese. Methods, We classified 110 healthy volunteers as rapid metabolizers (RM), intermediate metabolizers (IM) or poor metabolizers (PM) of CYP2C19 by genotyping. Breath samples were collected at 10-min intervals for 60 min after dosing with 100 mg [13C]-pantoprazole. Changes in the carbon isotope ratios (13CO2/12CO2) in carbon dioxide in breath samples were measured and expressed as a delta-over-baseline (DOB) ratio (,). Of the 110 subjects, twenty-two randomly selected subjects underwent intragastric pH monitoring on day 7 of dosing with 30 mg of lansoprazole. Results, The DOB values of RMs were the highest and those of PMs the lowest of the three groups. Statistically significant differences were observed in the area-under-the-curve (AUC)20,60 min of DOB among the three groups. The mean 24-h intragastric pHs attained by lansoprazole 30 mg for 7 days were inversely correlated with the AUC20,60 min of DOB. Conclusions, [13C]-pantoprazole breath test can easily estimate the individual activity of CYP2C19 and predict the efficacy of a PPI (i.e. lansoprazole). This test would be useful for individualized medicine with a PPI. [source] Clinical trial: intragastric acid control in patients who have Barrett's oesophagus,comparison of once- and twice-daily regimens of esomeprazole and lansoprazoleALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2009S. J. SPECHLER Summary Background, Gastric acid control is important for treatment of gastro-oesophageal reflux disease associated with Barrett's oesophagus. Substantial indirect evidence suggests that gastric acid control may have a chemopreventive role in Barrett's oesophagus. Aim, To compare the pharmacodynamic efficacy of esomeprazole and lansoprazole at two dosages for intragastric pH control with Barrett's oesophagus. Methods, Patients with Barrett's oesophagus received open-label consecutive treatment (a 15-day period of once-daily dosing followed by a 10-day period of twice-daily dosing) with esomeprazole (40-mg capsules) and lansoprazole (30-mg capsules) in random order with no washouts. Twenty-four-hour intragastric pH was recorded on the last day of each dosing period. The primary end point was the percentage of time with intragastric pH > 4.0. Results, In the per-protocol once- (n = 46) and twice-daily (n = 41) analyses, the percentage of time with intragastric pH > 4.0 was significantly (P < 0.0001) longer after once- (67.1%) or twice-daily (81.2%) esomeprazole than after once- (50.8%) or twice-daily (64.3%) lansoprazole. The proportion of patients with intragastric pH > 4.0 for >12 h was significantly higher for esomeprazole than lansoprazole with once- (P = 0.004) and twice-daily (P = 0.016) dosing. Conclusion, Esomeprazole 40 mg is significantly more effective than lansoprazole 30 mg in controlling intragastric pH with Barrett's oesophagus. [source] The clinical safety of long-term lansoprazole for the maintenance of healed erosive oesophagitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2009J. W. FRESTON Summary Background, The clinical safety of long-term lansoprazole therapy for the maintenance of healed erosive oesophagitis has not been extensively studied in clinical trials. Aim, To assess the long-term clinical safety of dose-titrated lansoprazole as maintenance therapy for up to 82 months in subjects with healed erosive oesophagitis. Methods, Clinical safety was assessed by monitoring adverse events (AEs), laboratory data including serum gastrin levels, and endoscopy. Results, Mean duration (± s.d.) of lansoprazole treatment during the titrated open-label period was 56 ± 24 months (range <1,82 months). Overall, 189 of 195 (97%) subjects experienced a total of 2825 treatment-emergent AEs. Most AEs occurred during the first year of treatment, were mild-to-moderate in severity and resolved while on treatment. Of 155 serious AEs (in 74 subjects), only two (colitis and rectal haemorrhage in one subject) were considered treatment-related. Sixty-nine of 195 subjects (35%) experienced 187 treatment-related AEs, with diarrhoea (10%), headache (8%) and abdominal pain (6%) being the most common. Gastrin levels ,400 pg/mL were seen in 9% of subjects; hypergastrinemia was not associated with gastro-intestinal AEs or nodules/polyps. Conclusions, Lansoprazole maintenance therapy for up to 6 years is safe and well tolerated in subjects with healed erosive oesophagitis. [source] | ||||||||||||||||||||||||||||