Prevacid
Role of capsaicin-sensitive sensory neurons and nitric oxide in the protective effect of lansoprazole, a proton pump inhibitor, on the gastric mucosa in rats.

Murakami I, Satoh H, Asano S, Maeda R.

Pharmaceutical Research Laboratories III, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.

The mucosal protective effect of lansoprazole, a proton pump inhibitor, was examined in ethanol- and acidified taurocholate-induced rat gastric lesion models. The formation of gastric lesions was markedly inhibited by prostaglandin E2 but hardly inhibited by cimetidine, ranitidine and famotidine. Lansoprazole (3-30 mg/kg, p.o.) inhibited the formation of gastric lesions in a dose-dependent manner, with ID50 values of 8.5 (ethanol) and 4.1 mg/kg, p.o. (acidified taurocholate). The protective effect of lansoprazole was significantly decreased by functional ablation of capsaicin-sensitive sensory neurons or prior administration of indomethacin or N(omega)-nitro-L-arginine methyl ester (L-NAME), a selective inhibitor of nitric oxide (NO) synthesis. The inhibitory effect of L-NAME was antagonized by prior administration of L-arginine, a substrate of endogenous NO, but not D-arginine. The antisecretory effect of lansoprazole on the basal acid secretion in pylorus-ligated rats was not affected by any of these treatments. Lansoprazole (5 and 15 mg/ml) administered directly into the gastric chamber obviously increased both the production of NO in the mucosa and mucosal blood flow, which was prevented by pretreatment with L-NAME. These results suggest that capsaicin-sensitive sensory neurons, NO and prostaglandins are involved in the mucosal protection afforded by lansoprazole possibly via an increase in mucosal blood flow, but are not involved in the antisecretory action of lansoprazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8912915&dopt=Abstract lansoprazole Prevacid



Prevacid
Metabolic interactions of the proton-pump inhibitors lansoprazole, omeprazole and pantoprazole with other drugs.

Meyer UA.

Department of Pharmacology, Biozentrum of the University of Basel, Switzerland.

PURPOSE: To analyse the metabolism of the proton-pump inhibitors lansoprazole, omeprazole and pantoprazole by cytochrome P450 (CYP) enzymes, and to assess the consequences for drug-drug interactions. RESULTS OF DATA ANALYSIS: Lansoprazole, omeprazole and pantoprazole are extensively metabolized by several human cytochromes P450, most prominently by mephenytoin hydroxylase (CYP2C19) and nifedipine hydroxylase (CYP3A4). Only pantoprazole is also metabolized to a significant extent by a conjugating enzyme, a cytosolic sulfotransferase. The substrates and inhibitors of CYP2C19 and CYP3A4 and the known genetic polymorphism of CYP2C19 explain some but not all of the interactions of lansoprazole, and particularly the interactions of omeprazole with carbamazepine, diazepam, phenytoin and theophylline or caffeine. Both lansoprazole and omeprazole apparently also induce cytochromes P450 such as CYP1A2. This effect appears at lower doses of omeprazole in poor metabolizers of omeprazole. Of these three drugs, pantoprazole has by far the lowest potential for interactions, both in vitro (in microsomal studies) and in volunteer studies. CONCLUSIONS: Proton-pump inhibitors interact with and are metabolized by several human cytochromes P450, but only pantoprazole is also metabolized by a sulfotransferase. This may partly explain why, in this group of proton-pump inhibitors, pantoprazole has the lowest potential for interactions with other drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8930576&dopt=Abstract lansoprazole Prevacid



Prevacid
Effect of lansoprazole in mono-, dual-, or triple therapy on Helicobacter pylori eradication.

Kawano S, Murakami M, Saita H, Tsuji S.

Department of Medicine, Osaka University, School of Medicine, Japan.

The effect of lansoprazole, in mono, dual, or triple therapy, on the eradication of Helicobacter pylori was reviewed. Lansoprazole has a cytotoxic action against this organism, the MIC being 2.56-5.25 micrograms/ml. In in vitro experiments, lansoprazole exerts direct action, i.e., antibacterial activity of lansoprazole against H. pylori and also inhibits urease activity. With antibiotics, this drug has a synergistic effect against H. pylori. In clinical studies, the eradication rate of H. pylori with lansoprazole is 0%-25% with monotherapy, 22%-33% with dual therapy (of AMPC), and 75%-82.4% with triple therapy with metronidazole and antibiotics. We inves-tigated the effect of lansoprazole on the eradication of H. pylori with dual therapy, the other agent being amoxicillin (AMPC). The eradication rate was 0% when 30 mg lansoprazole was employed as monotherapy, 33% for dual therapy with 30 mg lansoprazole and 1 g AMPC, and 71% for dual therapy with 60 mg lansoprazole and 1 g AMPC, the eradication rate with 60 mg lansoprazole and 1 g AMPC being significantly higher than that with the lower dose of lansoprazole. This result suggested that the greater acid suppression brought about by lansoprazole 60 mg enhances the action of AMPC, indicating that lansoprazole, when used with AMPC, is effective for eradication of H. pylori.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8959517&dopt=Abstract lansoprazole Prevacid



Prevacid
[Erradicating treatment of Helicobacter pylori with lansoprazole and amoxicillin in duodenal ulcer patients]

[Article in Spanish]

Gisbert JP, Boixeda D, Alvarez Baleriola I, Martin de Argila C, Bermejo F, Aller R.

Servicio de Gastroenterologia, Hospital Ramon y Cajal, Madrid.

OBJECTIVE: To study the efficiency of the combination lansoprazole and amoxicillin on the eradication of Helicobacter pylori and duodenal ulcer healing. METHODS: Twenty-nine duodenal ulcer patients infected with H. pylori were prospectively studied (mean age, 46 +/- 11 years, 90% males). During endoscopy biopsies were obtained from gastric antrum and body for histologic examination (H & E); a urea breath test with 13C was also performed. Therapy with lansoprazole 30 mg/12 h and amoxicillin 500 mg/6 h for two weeks was prescribed. One month after completing therapy another endoscopy was performed (with biopsies obtained from gastric antrum and body) and again a urea breath test performed. Eradication was defined as the absence of H. pylori by both diagnostic methods. RESULTS: Eradication was achieved in 48% of patients (n = 14). Ulcer healing was obtained in 62% of cases (n = 18). When eradicating therapy was successful the percentage of healing reached 100%, versus 27% in those patients with persisting infection (p < 0.001). In patients with eradication obtained an histological improvement was noted both at gastric antrum and body, whereas when therapy failed no significant changes were observed. In all cases compliance with therapy was completed, and in no patient were secondary effects observed. CONCLUSION: The association of lansoprazole and amoxicillin at the administered doses has a low efficiency on H. pylori eradication in duodenal ulcer patients. Further studies are warranted to definitely assess the eradicating efficiency of such combination and also to determine the optimal dose of its components, the minimal duration of therapy and the ideal moment for its administration.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8966319&dopt=Abstract lansoprazole Prevacid



Prevacid
Time to maximum effect of lansoprazole on gastric pH in normal male volunteers.

Bell NJ, Hunt RH.

Department of Medicine, McMaster University Medical Centre, Hamilton, Ontario, Canada.

BACKGROUND: The time to maximum inhibition of gastric acidity resulting from repeated oral dosing with lansoprazole 30 mg daily for 7 days was studied in nine healthy male volunteers. METHODS: Twenty-four hour intragastric pH monitoring was performed before treatment and on days 1, 3, 5 and 7 of dosing with lansoprazole. Blood samples were taken for the estimation of plasma lansoprazole concentrations. RESULTS: Lansoprazole 30 mg increased mean 24-h intragastric pH to 3.57 on day 1 compared with baseline mean pH of 2.11 (P < 0.05). The mean intragastric pH during the morning period (08.00-13.00 h) was significantly higher on days 3, 5 and 7 than on day 1, but no consistent differences between day 1, 3, 5 and 7 were noted for subsequent periods (13.00-18.00, 18.00-21.00 and 23.00-07.00 h). There were no differences in mean pH between days 3, 5 and 7. Intragastric pH was maintained above pH 3 for 54.7, 60.1, 61.9 and 67.4% of the time on days 1, 3, 5 and 7, respectively. Lansoprazole pharmacokinetic parameters did not change with daily dosing. The area under the lansoprazole plasma concentration-time curve correlated with the intragastric pH (P < 0.005). CONCLUSIONS: Lansoprazole 30 mg raised intragastric pH significantly from baseline on day 1 to a maximum effect as early as 6 h after the first dose. The degree and duration of acid suppression confirm the usefulness of lansoprazole for the treatment of acid-related disorders.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8971286&dopt=Abstract lansoprazole Prevacid