- 35 Downloads
Lansoprazole is a benzimidazole derivative that effectively decreases gastric acid secretion, regardless of the primary stimulus, via inhibition of gastric H+,K+-adenosine triphosphatase (ATPase). It provides effective symptom relief and healing of peptic ulcer and reflux oesophagitis after 4 to 8 weeks of therapy and appears to prevent recurrence of lesions when administered as maintenance therapy.
When administered at therapeutic dosages, lansoprazole produced higher healing rates than ranitidine or famotidine in patients with duodenal and gastric ulcers. Lansoprazole heals duodenal ulcers more rapidly than ranitidine or famotidine. Relief of ulcer symptoms in lansoprazole recipients is at least equivalent to, and tends to be more rapid than, that in patients receiving histamine H2-receptor antagonists. In comparisons with omeprazole 20 mg/day, lansoprazole 30 mg/day produced duodenal ulcer healing more rapidly and reduced ulcer pain to a greater extent at 2 weeks, but overall healing rates were similar after 4 weeks of therapy.
At therapeutic dosages, lansoprazole produces superior healing and symptom relief of reflux oesophagitis in comparison with ranitidine, and it tends to relieve heartburn more effectively than omeprazole, although both agents produce equivalent healing. Healing of peptic ulcers or reflux oesophagitis refractory to histamine H2-receptor antagonists occurs after 8 weeks in the majority of patients treated with lansoprazole, and lansoprazole and omeprazole demonstrate similar efficacy in patients with refractory peptic ulcers. In patients with Zollinger-Elli-son syndrome, lansoprazole effectively controls mean basal gastric acid output.
Lansoprazole is generally well tolerated in clinical trials. The incidence of adverse effects is similar to that of omeprazole, ranitidine and famotidine in comparative studies.
Combination therapy with lansoprazole and antibacterial agents such as amoxicillin, tinidazole, roxithromycin and/or metronidazole appears to eradicate Helicobacter pylori in 22 to 80% of patients with this organism. Limited data also suggest that lansoprazole may have superior activity against H. pylori in comparison with omeprazole, although the clinical relevance of this preliminary finding requires further confirmation.
Thus, lansoprazole may be considered as an alternative to existing antisecretory agents available for the treatment of acid-related disorders, particularly because it may provide more rapid healing and relief of symptoms.
Lansoprazole is metabolised to active sulphenamide derivatives in gastric parietal cells. These metabolites inactivate the sulfhydryl group of H+,K+-adenosine triphosphatase (ATPase), the enzyme catalysing the final step of the gastric acid secretion pathway, thus inhibiting both centrally and peripherally mediated gastric acid secretion. Increased mucosal oxygenation or bicarbonate secretion induced by lansoprazole may also protect the gastric mucosa from injury.
In healthy volunteers, single and multiple oral doses of lansoprazole inhibit both basal and stimulated gastric acid secretion, although the normal circadian rhythm of acid secretion is maintained. Inhibition of gastric acid secretion is dose-related over the range of 15 to 60mg and is approximately 80 to 97% after a single 30mg dose. 90% inhibition was noted after 7 days of therapy with lansoprazole 30 mg/day in 1 study. Inhibition of gastric acid secretion was also dose proportional in patients with a history of duodenal ulcer who received single or daily (for 7 days) doses of lansoprazole 10 to 30mg.
Unlike histamine H2-receptor antagonists, lansoprazole inhibits daytime and nocturnal acid secretion regardless of whether it is administered in the morning or the evening. Gastric acid inhibition is also similar when lansoprazole is administered before or after a meal. Lansoprazole has no effect on postprandial digestive function or gastric emptying. Lansoprazole inhibits pepsin secretion and activity in healthy volunteers, with greater inhibition observed when the drug is administered at night compared with in the morning.
In several studies conducted in patients with peptic ulcer, serum gastrin levels approximately doubled after 2 months of treatment with lansoprazole 30 to 60 mg/day, although levels returned to baseline within 1 to 12 weeks of discontinuing therapy. In a longer term study using the same dosages of lansoprazole, basal gastrin levels increased to 4 times normal values after 4 weeks, but no further increases were observed during the following 4 years of treatment. No significant change in enterochromaffin-like (ECL) cell density was observed in about 350 patients with acid-related disorders after 8 weeks of therapy with lansoprazole at dosages of up to 60 mg/day. However, ECL cell hyperplasia was seen in some patients with refractory peptic ulcers or reflux oesophagitis who received lansoprazole 30 to 120 mg/day for 30 months in 1 study, but no patient developed dysplastic lesions or carcinoids.
Eradication of Helicobacter pylori is associated with healing and maintenance of disease remission in patients with peptic ulcer. Lansoprazole has antimicrobial activity against H. pylori in vitro and is as effective as tripotassium dicitrato bismuthate (colloidal bismuth subcitrate) and 4 times more potent than omeprazole for eradication of this organism in vitro. H. pylori urease is also inhibited by lansoprazole in vitro.
Lansoprazole is acid labile and is therefore administered as an enteric-coated formulation. Maximum serum lansoprazole concentrations (Cmax) of 0.75 to 1.15 mg/L are reached within 1.5 to 2.2 hours of oral administration of a 30mg dose to healthy volunteers. Cmax values are dose-proportional over the range 15 to 60mg. Although bioavailability shows marked interindividual variability, Cmax and bioavailability are not significantly altered by administration of multiple drug doses. Concomitant food intake delayed absorption, and reduced Cmax and bioavailability in some studies, but bioavailability was not altered in others. The bioavailability of lansoprazole was not affected by prior administration of antacid.
In the serum, lansoprazole is metabolised to 2 main excretory metabolites, lansoprazole sulphone and hydroxy-lansoprazole. Single and multiple doses of oral lansoprazole 15 to 60mg have a plasma elimination half-life of between 1.3 and 1.7 hours in healthy volunteers. Lansoprazole has not been recovered from the urine in an unchanged form. Conjugated and unconjugated hydroxylated metabolites of the drug are renally excreted, although they account for only 14 to 23% of the total administered dose of lansoprazole.
In healthy elderly volunteers, compared with younger volunteers, Cmax of lansoprazole was not significantly different, but area under the concentration-time curve values were increased and elimination was prolonged. Similarly, elimination was prolonged in patients with severe liver disease and in older patients (mean age 69 years) with mild renal impairment (creatinine clearance 2.4 to 3.6 L/h). In patients with more severe renal impairment (creatinine clearance less than 1.2 L/h), elimination was not significantly different from that of healthy volunteers.
Lansoprazole 30 mg/day provided effective symptom relief and healing of duodenal ulcer in 75 to 100% of patients after 4 weeks’ therapy in noncomparative and comparative trials. Similarly, in patients with gastric ulcer, the same dosage of lansoprazole produced healing rates of 50 to 79% after 4 weeks and 87 to 100% after 8 weeks.
Lansoprazole 30 mg/day produced superior healing rates in patients with duodenal and gastric ulcers compared with ranitidine 300 mg/day and was slightly more effective than famotidine 40 mg/day after 4 weeks of therapy in patients with duodenal ulcer. In patients with gastric ulcer, lansoprazole produced higher healing rates and faster healing than famotidine 20mg twice daily. Lansoprazole 30 mg/day healed duodenal ulcers more rapidly than therapeutic dosages of ranitidine or famotidine. Reductions in ulcer symptoms were at least equivalent in lansoprazole-treated patients with peptic ulcers and in patients who received histamine H2-receptor antagonists, but tended to be achieved more rapidly in lansoprazole recipients in some studies.
Lansoprazole 30 mg/day produced duodenal ulcer healing more rapidly than omeprazole 20 mg/day in 2 of 3 published studies (2-week healing rates of 74 to 88% vs 58 to 82%) and reduced ulcer pain to a greater extent after 2 weeks in 1 study, although healing rates were similar (at least 94%) after 4 weeks. In patients with gastric ulcer, lansoprazole produced superior healing rates to omeprazole after 8 weeks in an intent-to-treat analysis and relief of gastric pain tended to occur more rapidly with lansoprazole. However, healing rates were similar in both groups at 4 and 8 weeks in a per protocol analysis of the data.
Lansoprazole 30 mg/day produced endoscopically measured healing in 85 to 97% of patients with reflux oesophagitis after 8 weeks’ treatment and provided rapid relief of symptoms. Both healing and symptom relief were achieved more effectively with lansoprazole than with ranitidine 300 mg/day or placebo. Lansoprazole tended to relieve symptoms of oesophagitis more effectively than omeprazole 20 mg/day at 2 or 4 weeks, although both agents produced equivalent healing after 4 and 8 weeks. Patients with Barrett’s oesophagus were also effectively treated with lansoprazole 30 to 60 mg/day; in 1 study the beneficial effects of the drug were maintained for a mean of 2.7 years.
Preliminary results show that recurrence of duodenal ulcer or reflux oesophagitis was effectively prevented during 1 year of treatment with lansoprazole 15 or 30 mg/day, respectively, compared with placebo, in patients with healed lesions. Maintenance therapy with lansoprazole 15, 30 or 60 mg/day prevented or significantly reduced the incidence of recurrence for periods of up to 4 years in patients with healed lesions previously refractory to histamine H2-receptor antagonists.
Lansoprazole 30 or 60 mg/day generally produces healing of peptic ulcers or reflux oesophagitis refractory to histamine H2-receptor antagonists in 69 to 100% of patients after 8 weeks. Lansoprazole 30 mg/day and omeprazole 20 or 40 mg/day had similar efficacy in 2 studies conducted in patients with refractory peptic ulcers.
Although data concerning eradication rates with lansoprazole monotherapy are scarce, in clinical studies, lansoprazole 15 or 30 mg/day for 2 to 8 weeks appears to clear H. pylori from the gastric mucosa in 12 to 76% of patients with gastric or duodenal ulcers, and preliminary findings suggest that it may be more effective than omeprazole in this regard. Combination therapy with lansoprazole and antibacterial agents increased H. pylori eradication rates and healing of peptic ulcers compared with lansoprazole monotherapy. However, the incidence of ulcer recurrence after discontinuation of lansoprazole in patients in whom H. pylori infection has been eradicated requires further study.
In patients with Zollinger-Ellison syndrome, lansoprazole 15 to 180 mg/day controlled mean basal gastric acid output (less than 10 mmol/h), and preliminary evidence suggests that it is as effective as omeprazole 20 to 160 mg/day in patients with this disease.
Lansoprazole 15 to 60 mg/day is generally well tolerated in short term (up to 8 weeks) clinical trials. The incidence of adverse effects with placebo or therapeutic dosages of lansoprazole or comparator agents was similar. Tolerability data from 4749 volunteers or patients who received lansoprazole 7.5 to 120 mg/day (most commonly 30 mg/day) in clinical trials showed that the most frequent adverse events were gastrointestinal (9% of patients), particularly diarrhoea. Headache (4.7%), dizziness (1%), skin disorders (1.7%) and respiratory tract symptoms were also reported. The incidence of withdrawal from lansoprazole therapy was 1.2%. 1678 volunteers or patients received comparator drugs in these studies; the incidence of withdrawal from treatment was 1.1% with ranitidine, 0.1% with famotidine and 2.0% with omeprazole.
In clinical studies, laboratory abnormalities were uncommon in lansoprazole recipients, although serum gastrin levels increased in almost all studies, and increases in liver enzyme levels, haematocrit, haemoglobin levels, urinary protein excretion and uric acid levels were reported in a small number of patients. No clinically significant changes in steroid or thyroid hormone metabolism have been reported with lansoprazole therapy. Lansoprazole does not appear to significantly interact with other drugs metabolised by the cytochrome P450 enzyme system.
Studies assessing long term tolerability are scarce and will need to be conducted before the tolerability profile of lansoprazole can be fully elucidated.
Dosage and Administration
Although dosage recommendations vary from country to country, lansoprazole 15 or 30 mg/day for up to 4 weeks is generally administered for the short term treatment of patients with duodenal ulcer, while 30 mg/day for up to 8 weeks is recommended for treatment of patients with gastric ulcer or reflux oesophagitis. In patients with lesions refractory to histamine H2-receptor antagonist therapy, lansoprazole 30 to 60 mg/day for 8 to 12 weeks has been effective. Individualised dosages of 15 to 180 mg/day were effective at reducing gastric acid output to less than 10 mmol/h in patients with Zollinger-Ellison syndrome enrolled in clinical trials, and in some patients, dosage was reduced without loss of efficacy.
Lansoprazole is administered as encapsulated enteric-coated granules and is generally given in the morning before a meal.
KeywordsPeptic Ulcer Omeprazole Duodenal Ulcer Ranitidine Gastric Ulcer
Unable to display preview. Download preview PDF.
- 1.Barradell LB, Faulds D, McTavish D. Lansoprazole. A review of its pharmacodynamic and pharmacokinetic properties and its therapeutic efficacy in acid-related disorders. Drugs 1992; 44: 225–50Google Scholar
- 3.Clissold SP, Campoli-Richards DM. Omeprazole. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in peptic ulcer disease and Zollinger-Ellison syndrome. Drugs 1986; 32: 15–47Google Scholar
- 4.Inatomi N, Nagaya H, Ishisaka Y, et al. Effects of AG-1749 (lansoprazole) and its metabolites on acid secretion and experimental ulcers [in Japanese]. Yakuri to Chiryo 1991; 19: 477–86Google Scholar
- 5.Fryklund J, Torven A, Stålbom B-M, et al. Gastric H,K-ATPase and mRNA-levels in the rat after long term treatment with omeprazole, lansoprazole or pantoprazole [abstract]. Gastroenterology 1993; 104 Suppl.: A82Google Scholar
- 6.Nagano K, Sato N. Proton pump inhibitors protect gastric mucosa from hemorrhagic shock-induced injury by improving mucosal oxygenation in rats [abstract]. Gastroenterol Jpn 1993; 28: 345Google Scholar
- 7.Inada I, Inatomi N, Satoh H. Effect of lansoprazole (AG-1749) on duodenal bicarbonate secretion in anesthetized rats [in Japanese]. Jpn J Pharmacol Ther 1992; 20: 4345–50Google Scholar
- 11.Bayati A, Varai E, Holstein B, et al. The recovery rate of acid secretion in rats is similar following inhibition by lansoprazole, pantoprazole and omeprazole [abstract]. Gastroenterology 1993; 104 Suppl.: A39Google Scholar
- 13.Hogan DL, Koss MA, Feitelberg S, et al. Single and repetitive administration of lansoprazole: effects on gastric acid secretion, pharmacokinetics and serum gastrin in old vs young subjects [abstract]. Gastroenterology 1991; 100: A84Google Scholar
- 15.Tada M, Murakami A, Karita M, et al. A study of gastric juice secretion-inhibitory effect of a proton pump inhibitor, AG-1749 [in Japanese]. Rynsho-Seijinbyo 1991; 21: 633–40Google Scholar
- 16.Tateno M, Nakamura N. Phase I study of lansoprazole (AG-1749) antiulcer agent. Capsule form [in Japanese]. Rinsho Iyaku 1991; 7: 51–62Google Scholar
- 17.Moules I, Garrett A, Brocklebank D, et al. Gastric acid inhibition by proton pump inhibitor lansoprazole is unaffected by food. Br J Clin Res 1993; 4: 153–61Google Scholar
- 18.Grant SM, Langtry HD, Brogden RN. Ranitidine. An updated review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in peptic ulcer disease and other allied diseases. Drugs 1989; 37: 801–70Google Scholar
- 19.Hongo H, Ohara S, Hirasawa Y, et al. Effect of lansoprazole on intragastric pH. Comparison between morning and evening dosing. Dig Dis Sci 1992; 37: 882–90Google Scholar
- 20.Matsuo Y, Takemoto T, Miwa T, et al. Clinical study of the inhibitory effect of AG-1749, a proton pump inhibitor, on nocturnal gastric acid secretion: evaluation of dosage and administration [in Japanese]. Yakuri to Chiryo 1990; 18: 4865–76Google Scholar
- 22.Miwa T. Administration of proton pump inhibitors induce dyspepsia or not? [in Japanese]. Exp Ther 1992; (629): 178-9Google Scholar
- 24.Sugiyama M, Ishikawa T, Aoki T, et al. Effect of lansoprazole (AG-1749) on gastric acid secretion — inhibition of insulin-stimulated acid secretion [in Japanese]. Shokakika 1991; 14: 183–93Google Scholar
- 25.Creutzfeldt W, Lamberts R. Is hypergastrinaemia dangerous to man?. Scand J Gastroenterol 1991; 26 Suppl.180: 179–91Google Scholar
- 27.Harasawa S, Miwi T. The effect of AG-1749 (lansoprazole) on gastric emptying and serum gastrin concentration in peptic ulcer patients [in Japanese]. Yakuri to Chiryo 1991; 19: 947–52Google Scholar
- 28.Bell NJV, Chiba N, Ringham GL, et al. Time to maximum effect of lansoprazole on gastric pH in male, normal volunteers (NV) [abstract]. Gastroenterology 1992; 102: A40Google Scholar
- 29.Bergmann JF, Forestier S, Joubert M. Evolution of gastrinemia after treatment with lansoprazole in duodenal ulcer (DU) and reflux esophagitis (RE) [abstract]. Gastroenterology 1993; 104 Suppl.: A42Google Scholar
- 30.Iwafuchi M, Watanabe H. Effects of a novel proton pump inhibitor AG-1749 (lansoprazole) on endocrine cell populations of human gastric fundic mucosa [abstract]. Gastroenterol Jpn 1993; 28: 346Google Scholar
- 31.Makiyama K, Umene Y, Murata I, et al. Clinical study on therapeutic effect of an antiulcer agent, lansoprazole, on gastric ulcer: with special reference to serum gastrin concentration [in Japanese]. Yakuri to Chiryo 1991; 19: 307–25Google Scholar
- 32.Misawa T, Chijiwa Y, Imazono Y, et al. Effects of lansoprazole, a gastric proton pump inhibitor on endocrine function and healing in patients with peptic ulcer [in Japanese]. Ther Res 1991; 12: 175–89Google Scholar
- 33.Ogoshi K, Kato T, Sato N, et al. Clinical study of AG-1749 (lansoprazole): effects on serum gastrin levels and gastric mucosal ECL cell density, etc [in Japanese]. Yakuri to Chiryo 1991; 19: 933–46Google Scholar
- 34.Brunner G, Arnold R, Fuchs W. Long-term management of acid peptic disease. Barcelona ’93-II United European Gastroenterology Week, International Symposium on Lansoprazole, 1993 Jul 19–24; BarcelonaGoogle Scholar
- 35.McTavish D, Buckley MM-T, Heel RC. Omeprazole. An updated review of its pharmacology and therapeutic use in acid-related disorders. Drugs 1991; 42: 138–70Google Scholar
- 36.Abe T, Sato S, Suzuki T, et al. Thirteen-week oral toxicity study of lansoprazole (AG-1749) in rats. Yakuri to Chiryo 1990; 18 Suppl.10: S2663–78Google Scholar
- 37.Ando T, Sasaki S, Mayahara H, et al. Morphological study on the stomach of the rats treated orally with lansoprazole (AG-1749) for 4 and 13 weeks [in Japanese]. Yakuri to Chiryo 1992; 20: 4325–34Google Scholar
- 38.Atkinson JE, Daly IW, Boite HF, et al. One-year oral gavage toxicity study of lansoprazole (AG-1749) in rats. Yakuri to Chiryo 1990; 18 Suppl.10: S2713–45Google Scholar
- 39.Atkinson JE, Daly IW, Wooding WL, et al. One-year oral toxicity study of lansoprazole (AG-1749) in beagle dogs. Yakuri to Chiryo 1990; 18 Suppl.10: S2747–72Google Scholar
- 41.Dorsch E, Jones J, Padgett C, et al. Lansoprazole heals moderate to severe reflux esophagitis. American College of Gastroenterology Meeting, 1991 Oct 14–16; BostonGoogle Scholar
- 42.Ogoshi K. Effects of lansoprazole on gastric endocrine cells [in Japanese]. Exp Ther 1992; (629): 176-7Google Scholar
- 43.Rubin W, Mackay R, Jennings D, et al. Electron microscopy of gastric oxyntic endocrine cells in patients treated with lansoprazole for 8 weeks [abstract 136]. Am J Gastroenterol 1992; 87: 1276Google Scholar
- 44.Eissele R, Brunner G, Fischer B, et al. Evaluation of enterochromaffin-like (ECL)-cell hyperplasia during long-term treatment with the proton pump inhibitor lansoprazole [abstract]. Gastroenterology 1993; 104 Suppl.: A74Google Scholar
- 45.Cadiot G, Lehy T, Ruszniewski P, et al. Gastric endocrine cell evolution in patients with Zollinger-Ellison syndrome. Influence of gastrinoma growth and long-term omeprazole treatment. Dig Dis Sci 1993; 38: 1307–17Google Scholar
- 48.Solcia E, Rindi G, Havu N, et al. Qualitative studies of gastric endocrine cells in patients treated long-term with omeprazole. Scand J Gastroenterol 1989; 24 Suppl. 166: 129–37Google Scholar
- 53.Bigard MA, Joubert M, de Meynard C. Complete prevention by lansoprazole of aspirin induced gastric lesions in healthy subjects [abstract]. Gastroenterology 1991; 100: A34Google Scholar
- 54.Daneshmend TK, Sharma HK, Bhaskar NK, et al. Acid inhibition and mucosal protection with a new proton pump inhibitor [abstract]. Gut 1989; 30 (10): A1483Google Scholar
- 58.Figura N, Bugnoli M, Armellini D, et al. Activities of omeprazole and lansoprazole against Helicobacter pylori in vitro [abstract]. Hepatogastroenterology 1994; 41: 92–3Google Scholar
- 61.Nagata K, Satoh H, Iwahi T, et al. Potent inhibitory action of the gastric proton pump inhibitor lansoprazole against urease activity of Helicobacter pylori: unique action selective for//. pylori cells. Antimicrob Agents Chemother 1993; 37: 769–74Google Scholar
- 62.Nakagawa A, Ooka T, Kim H, et al. Phase I study of lansoprazole (AG-1749), antiulcer agent. Tablet form [in Japanese]. Rinsho Iyaku 1991; 7: 33–50Google Scholar
- 63.Delhotal-Landes B, Cournot A, Vermerie N, et al. The effect of food and antacids on lansoprazole absorption and distribution. Eur J Drug Metab Pharmacokinet 1991; (Special Issue No. III): 315-20Google Scholar
- 67.Miwa K, Mitani M, Tsukamoto T, et al. Metabolic fate of AG-1749, a new proton pump inhibitor, in rats, mice, and dogs [in Japanese]. Yakuri to Chiryo 1990; 18: 3413–35Google Scholar
- 68.Curi-Pedrosa R, Pichard L, Bonfils C, et al. Major implication of cytochrome P4503A4 in the oxidative metabolism of the antisecretory drugs omeprazole and lansoprazole in human liver microsomes and hepatocytes [abstract]. Br J Clin Pharmacol 1993; 36: 156Google Scholar
- 69.Delhotal B, Flouvat B, Cournot A, et al. Pharmacocinétique d’un nouvel inhibiteur de la pompe à protons gastrique. Le lansoprazole chez les sujets à risque. In: Brès & Panis, editors. Pharmacocinétique: de la recherche à la clinique. Paris: John Libbey Eurotext, 1992: 242-7Google Scholar
- 70.Coste T, Logeais C, Delhotal-Landes B, et al. Pharmacokinetics of lansoprazole after repeated administration in cirrhosis patients [abstract]. Gastroenterology 1993; 104 Suppl.: A59Google Scholar
- 71.Nogami H, Obata T, Takaguchi K, et al. Clinical effect of lansoprazole in treatment of peptic ulcer; healing rate of S2 stage [in Japanese]. Shinyaku to Rinsho 1994; 43: 595–604Google Scholar
- 72.Kitani M, Morisako K, Tanaka T, et al. Clinical effect of lansoprazole on patients with gastric and duodenal ulcer: Healing rate of S2 stage [in Japanese]. Yakuri to Chiryo 1994; 22: 1565–72Google Scholar
- 73.Aaronson R, Dorsch E, Padgett C, et al. Lansoprazole heals duodenal ulcers [abstract]. American College of Gastroenterology Meeting, 1991 Oct 14–16; BostonGoogle Scholar
- 75.Licht H, Andrieu J, Bognel JC, et al. Lansoprazole versus ranitidine dans le traitment des ulcers duodenaux: résultats d’un essai multicentrique contrôle, randomise, en double insu sur groupes paralleles. Med Chirurg Dig 1990; 19 (4): 251–5Google Scholar
- 78.Takemoto T, Namiki M, Goto Y, et al. A study of clinical usefulness of lansoprazole (AG-1749) in treating duodenal ulcer: a comparison with famotidine by the multiclinic, double-blind, controlled technique [in Japanese]. Rinsho-Seijinbyo 1991; 21: 613–31Google Scholar
- 79.Takemoto T, Namiki M, Goto Y, et al. Studies of clinical usefulness of lansoprazole (AG-1749) in the treatment of gastric and duodenal ulcers. A study of usefulness of AG-1749 at a dosage of 30 mg daily, using famotidine as the control drug [in Japanese]. Clin Adult Dis 1991; 21: 975–93Google Scholar
- 81.Ekström P, Unge P, Ahlberg J, et al. Lansoprazole vs omeprazole in active duodenal ulcer — a healing study [abstract 34]. Scand J Gastroenterol 1992; 27 Suppl.190: 40Google Scholar
- 82.Louw JA, van Rensburg C, Simjee AE, et al. Lansoprazole versus omeprazole in duodenal ulcer healing [abstract]. S Afr Med J 1993; 83: 777Google Scholar
- 84.Lanza F, Goff J, Silvers D, et al. Lansoprazole for one year prevents recurrence of duodenal ulcer [abstract]. Gastroenterology 1994; 106: A122Google Scholar
- 85.Takemoto T, Okazaki Y, Tada M, et al. Studies of clinical usefulness of lansoprazole (AG-1749) in the treatment of gastric and duodenal ulcers. A clinical early phase II study [in Japanese]. Clin Adult Dis 1991; 21: 769–83Google Scholar
- 86.Movva R, Sahba B, Jennings D, et al. Lansoprazole heals gastric ulcers [abstract]. Gastroenterology 1992; 102: A129Google Scholar
- 89.Londong W, Hotz J, Kleinert R, et al. Dose finding study in gastric ulcer with lansoprazole, a new proton pump inhibitor [abstract PP670]. The World Congresses of Gastroenterology, 1990 Aug 26–31; SydneyGoogle Scholar
- 90.Takemoto T, Namiki M, Goto Y, et al. A study of clinical usefulness of lansoprazole (AG-1749) in treating gastric ulcer: a comparison with famotidine by the multiclinic, double-blind, controlled technique [in Japanese]. Rinsho-Seijinbyo 1991; 21: 327–45Google Scholar
- 91.Florent Ch, Forestier S, Joubert-Collin M. Lansoprazole versus omeprazole: efficacy and safety in acute gastric ulcer [abstract]. Gastroenterology 1993; 104 Suppl.: A80Google Scholar
- 92.Jhala NC, McFarland M, Brightman S, et al. Effect of short term treatment with lansoprazole on H. pylori and antral gastritis in patients with duodenal ulcers [abstract 675]. Meeting of American Gastroenterological Association, 1992 May 9-14; San FranciscoGoogle Scholar
- 93.Lamouliatte H, Bernard PH, Cayla R, et al. Effect of lansoprazole against Helicobacter pylori in vivo [abstract]. Gastroenterology 1992; 102: A106Google Scholar
- 94.Tamura K, Yamamoto A, Shinoyama N, et al. Clinical effect of AG-1749 on gastric ulcer: histological change of gastric mucosa and effect on Helicobacter pylori [in Japanese]. Yakuri to Chiryo 1990; 18: 4877–90Google Scholar
- 95.Louw JA, Lücke W, Jasklewicz K, et al. Helicobacter pylori suppression by the proton pump inhibitors (PPI’s): a class effect? [abstract]. S Afr Med J 1993; 83: 784Google Scholar
- 96.Burette A, Glupczynski Y, DePrez C, et al. Lansoprazole plus roxithromycin and metronidazole for eradication of H. pylori: results of a single-blind pilot study [abstract]. Acta Gastroenterol Belg 1993; Suppl.: 131Google Scholar
- 97.De Korwin JD, Joubert M, Bazin N, et al. Lansoprazole versus lansoprazole plus antibiotics in the treatment of Helicobacter pylori gastric infection [abstract]. Gastroenterology 1993; 104 Suppl.: A67Google Scholar
- 98.Hatlebakk JG, Nesje LB, Hausken T, et al. Lansoprazole and amoxicillin oral suspension in the treatment of peptic ulcer disease [abstract]. Eur J Gastroenterol Hepatol. In pressGoogle Scholar
- 100.Kiyomizu T, Akamizu Y, Fujimori T, et al. Eradication of Helicobacter pylori and trends in serum antibody titres — clinical significance of serum antibody titres [in Japanese]. Shinyaku to Rinsho 1994; 43: 165–71Google Scholar
- 101.Sekiguchi T, Matsuzaki T, Horikoshi T, et al. Open study of the clinical effects of lansoprazole in the treatment of reflux oesophagitis. Drug Invest 1992; 4: 422–34Google Scholar
- 102.Bardhan KD, Long R, Hawkey CJ, et al. Lansoprazole, a new proton-pump inhibitor, vs ranitidine in the treatment of reflux erosive esophagitis [abstract]. Gastroenterology 1991; 100: A30Google Scholar
- 103.Robinson MG, Kogut D, Jennings D, et al. Lansoprazole heals erosive reflux esophagitis better than ranitidine [abstract 2178]. Meeting of American Gastroenterological Association, 1992 May 9-14; San FranciscoGoogle Scholar
- 104.Benhaim MC, Evereux M, Salducci J, et al. Lansoprazole and ranitidine in treatment of reflux oesophagitis: double blind comparative trial [abstract]. Gastroenterology 1990; 98: A20Google Scholar
- 105.Corallo J, Vicari F, Forestier S, et al. Lansoprazole in acute treatment of reflux esophagitis [abstract]. Gastroenterology 1993; 104 Suppl.: A58Google Scholar
- 106.Hatlebakk JG, Berstad A, Carling L, et al. Lansoprazole versus omeprazole in short-term treatment of reflux oesophagitis. Results of a Scandinavian multicentre trial. Scand J Gastroenterol 1993; 28: 224–8Google Scholar
- 108.Robinson M, Lanza F, and the Lansoprazole Study Group. Lansoprazole for one year prevents recurrence of erosive reflux esophagitis [abstract]. Gastroenterology 1994; 106: A166Google Scholar
- 109.Swarbrick ET, Gough AL, Christian J, et al. Prevention of recurrence of oesophageal stricture. A comparative study of lansoprazole and high dose ranitidine [abstract]. Gastroenterology 1994; 106: A189Google Scholar
- 110.Peters FTM, Kleibeuker JH. Barrett’s oesophagus and carcinoma. Recent insights into its development and possible prevention. Scand J Gastroenterol 1993; 28 Suppl. 200: 59–64Google Scholar
- 112.Sontag SJ, Schnell TG, Kurucar C, et al. Lansoprazole (LAN) heals erosive reflux esophagitis (ERE) in patients (PTS) with Barrett’s esophagus (BE) [abstract 74]. Am J Gastroenterol 1993; 88: 1499Google Scholar
- 113.Sampliner RE, Romero R, LaFleur L. Effect of up to 3 years of high dose lansoprazole on Barrett’s esophagus [abstract]. Gastroenterology 1994; 106: A172Google Scholar
- 114.Arakawa T, Higuchi K, Fukuda T, et al. H2-receptor antagonist-refractory ulcer: its pathophysiology and treatment. J Clin Gastroenterol 1991; 13 Suppl. 1: 129–33Google Scholar
- 115.Asaka M, Saito M, Takeda H, et al. Clinical evaluation of lansoprazole on H2-blocker resistant peptic ulcer [in Japanese]. Yakuri to Chiryo 1991; 19: 953–66Google Scholar
- 116.Yasutake K, Yoshimura Y, Oya M, et al. Efficacy of lansoprazole in the treatment of peptic ulcer refractory to H2 receptor antagonists [in Japanese]. Shokakika 1990; 13: 602–10Google Scholar
- 117.Robinson MG, Campbell DR, Sontag S, et al. Lansoprazole heals H2 resistant erosive reflux esophagitis [abstract]. Gastroenterology 1990; 98: A113Google Scholar
- 118.Delle Fave G, Annibale B, Helander H, et al. Omeprazole versus high dose ranitidine in H2-blocker-resistant duodenal ulcer patients. Eur J Gastroenterol Hepatol 1991; 3: 337–42Google Scholar
- 119.Saggioro A, Bortoluzzi F, Chiozzini G, et al. Ranitidine 600mg and resistant peptic ulcer disease. A retrospective analysis. Drug Invest 1990; 2: 67–9Google Scholar
- 122.Harlet L, De Boever G, Descamps C, et al. Comparison of lansoprazole and omeprazole in the treatment of resistant duodenal ulcer. Barcelona ’93-11 United European Gastroenterology Week, International Symposium on Lansoprazole, 1993 Jul 19-24; BarcelonaGoogle Scholar
- 123.Fléjou JF, Potet F, Lemaire M. Efficacy and safety of a 24-week treatment with lansoprazole (30 mg/day) following healing of peptic lesions resistant to H2 blockers [abstract]. Gastroenterology 1993; 104 Suppl.: A79Google Scholar
- 124.Sontag SJ, Richter J, Campbell D, et al. Lansoprazole (LAN) for one year prevents recurrence of resistant erosive reflux esophagitis (ERE) [abstract 73]. Am J Gastroenterol 1993; 88: 1499Google Scholar
- 126.Hirschowitz BI, Mohnen J, Shaw S. Zollinger-Ellison syndrome treated with lansoprazole [abstract]. Gastroenterology 1993; 104 Suppl.: A100Google Scholar
- 127.Pospai D, Vissuzaine Ch, Forestier S, et al. Efficacité du lansoprazole dans le traitement du syndrome de Zollinger-Ellison (SZE). Gastroenterol Clin Biol 1994; 18: A126Google Scholar
- 128.Ramdani A, Paul G, Ruszniewski Ph, et al. Comparative efficiency of lansoprazole and omeprazole on 24-hour intragastric pH measurement in 9 cases of Zollinger-Ellison syndrome [abstract]. Gastroenterology 1992; 102: A151Google Scholar
- 131.Gaetani M, Buratti P, Pasquali R, et al. Chronic oral administration with lansoprazole does not affect gonadotropin pulsatile pattern in healthy males [abstract]. Gastroenterology 1993; 104 Suppl.: A84Google Scholar
- 133.Misawa T. Proton pump inhibitors have effects on endocrine system or not? [in Japanese]. Exp Ther 1992; (629): 180-1Google Scholar
- 135.Cavanaugh JH, Park YK, Awni WM, et al. Effect of lansoprazole on antipyrine and ICG pharmacokinetics [abstract]. Gastroenterology 1991; 100 Suppl.: 40Google Scholar
- 137.Cavanaugh JH, Schneck DW, Mukherji D, et al. Lack of effect of concomitant lansoprazole on single-dose propranolol pharmacokinetics and pharmacodynamics [abstract]. Gastroenterology 1994; 106: A4Google Scholar
- 138.Braeckman RA, Winters EP, Cohen A, et al. Lack of effect of lansoprazole on warfarin pharmacokinetics and anticoagulation effect in healthy subjects [abstract PPDM 8277]. Phar-maceut Res 1991; 8 Suppl.: 3295Google Scholar
- 139.Cavanaugh JH, Locke C, Karol M. Lack of interaction of lansoprazole or omeprazole with prednisone [abstract 431]. Am J Gastroenterol 1993; 88: 1589Google Scholar
- 140.Karol MD, Mukherji D, Cavanaugh JH. Lack of effect of concomitant multi-dose lansoprazole on single-dose phenytoin pharmacokinetics in subjects [abstract]. Gastroenterology 1994; 106: A103Google Scholar
- 141.Granneman G, Winters EP, Locke CS, et al. Lack of effect of concomitant lansoprazole on steady-state theophylline pharmacokinetics [abstract]. Gastroenterology 1991; 100: A75Google Scholar
- 142.Meyer BH, Marée JS, Müller FO, et al. Lack of interaction between an oral contraceptive and lansoprazole or omeprazole [abstract]. African Pharmaceutical Society Congress, 1993 Sep 21–24Google Scholar
- 143.Higueret D, Coutelle C, Cassaigne A, et al. Effect of lansoprazole on gastric ADH activity in vitro [abstract]. Gastroenterology 1993; 104 Suppl.: A829Google Scholar
- 145.Goggins MG, O’Brion S, Kelleher B, et al. Protein-bound cobalamin absorption is significantly impaired by omeprazole [abstract W51]. Gut 1993; 34 Suppl.: S14Google Scholar