Prevacid
Autoradiographic demonstration of lansoprazole uptake sites in rat antrum and colon.

Nakamura M, Oda M, Akiba Y, Inoue J, Ito T, Tsuchiya M, Ishii H.

Department of Internal Medicine, Keio University, School of Medicine, Tokyo, Japan.

To investigate possible effects of lansoprazole other than its acid suppression through the parietal cell, uptake sites for lansoprazole were studied by autoradiography in rat antral and colon mucosa. Autoradiography was performed using two different methods, i.e., routine fixation and in vitro autoradiography on cryostat sections. Our results showed that the uptake sites for lansoprazole in the gastric antrum were located in the interstitial cells, including unmyelinated nerve fibers, whereas those in the colon mucosa corresponded to epithelial cells and some of the interstitial cells. With electron microscopy, the uptake sites for lansoprazole in the colon epithelial cells were seen exclusively near the apical plasma membrane. On the basis of these findings, lansoprazole may have effects on autonomic nerve and colon epithelial function as well as on acid secretion.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7594349&dopt=Abstract lansoprazole Prevacid



Prevacid
Long-term lansoprazole control of gastric acid and pepsin secretion in ZE and non-ZE hypersecretors: a prospective 10-year study.

Hirschowitz BI, Simmons J, Mohnen J.

The University of Alabama at Birmingham, Division of Gastroenterology and Hepatology, University Station, Birmingham, AL, USA. bhirschowitz gihep.uab.edu

BACKGROUND: The majority of patients with Zollinger-Ellison syndrome require lifelong treatment with proton pump inhibitors. AIMS: To determine the efficacy of lansoprazole control of acid and pepsin secretion over the long term in Zollinger-Ellison syndrome and non-Zollinger-Ellison syndrome hypersecretors. METHODS: Sixty-three hypersecretors (basal acid output > 15 mmol/h), 46 Zollinger-Ellison syndrome and 17 non-Zollinger-Ellison syndrome, with a total history of 15.4 and 19.2 years, respectively, were entered into a long-term prospective study using lansoprazole. Sixty-one were studied every 3 months for 1 year and then every 3-6 months up to 10 years during lansoprazole treatment with endoscopy, serum gastrin and gastric analysis, measuring both basal and stimulated pH and acid and pepsin secretion. Doses were individually optimized and adjusted to keep the basal acid output at < 5 mmol/h in intact patients and < 1 mmol/h in antrectomized Zollinger-Ellison syndrome patients. RESULTS: The dose of lansoprazole could not be predicted a priori from pre-treatment acid or pepsin output, serum gastrin, prior omeprazole dose or diagnosis or prior complications. The median dose was approximately 80 mg/day, with a wide range from 15 mg every other day to 360 mg/day, and generally stabilized by 12 months. However, as doses were adjusted over time for indications, almost half the patients required higher doses. With adjustments, the basal acid output was maintained in the target range in > 90% of intact patients and in 80% of antrectomized patients. Gastric juice pH increased from approximately 1.2 before therapy to > 3.4 during therapy. Serum gastrin in Zollinger-Ellison syndrome patients, after excluding five outliers, did not change over the course of therapy, but doubled in non-Zollinger-Ellison syndrome patients. There were no adverse events due to lansoprazole, and routine laboratory studies remained normal. CONCLUSIONS: The dose of lansoprazole for hypersecretors cannot be predicted, and thus needs to be optimized empirically on an individual basis. With continued periodic adjustments, almost half the patients required increased doses, while safe dose reduction was possible in only one-quarter. When individually optimized, lansoprazole proved to be safe and effective in the control of secretion for the treatment of both Zollinger-Ellison syndrome and non-Zollinger-Ellison syndrome hypersecretors for up to 10 years.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11683694&dopt=Abstract lansoprazole Prevacid



Prevacid
Lansoprazole reverses Helicobacter pylori-inhibited gastric epithelial cell growth.

Nakajima N, Kuwayama H, Iwasaki A, Arakawa Y.

Third Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.

Helicobacter pylori is associated with retarded healing and recurrence of peptic ulcer. Acid inhibitory agents, including proton pump inhibitors (PPIs), accelerate healing of peptic ulceration. Because epithelial cell proliferation is important for ulcer healing, we studied the effects of H. pylori and lansoprazole, a novel PPI, on gastric epithelial cell growth in vitro. Cell viability was significantly decreased when they incubated with 10(8) CFU/ml H. pylori. Nevertheless, all doses tested, from 10(6) to 10(8) CFU/ml H. pylori inhibited cell growth in a dose-dependent fashion. Co-incubation with AG-2000, an acid-converted derivative of lansoprazole, reversed H. pylori-inhibited cell growth. These results indicate that the antiulcer action of lansoprazole may involve a reversible effect on H. pylori-inhibited cell growth in addition to its well-established acid inhibitory action on parietal cells.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7594352&dopt=Abstract lansoprazole Prevacid



Prevacid
Lansoprazole inhibits oxygen-derived free radical production from neutrophils activated by Helicobacter pylori.

Suzuki M, Nakamura M, Mori M, Miura S, Tsuchiya M, Ishii H.

Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.

We studied the influence of lansoprazole on Helicobacter pylori-elicited neutrophil activation, including the oxidative burst and infiltration of gastric mucosa, and confirmed whether radiolabeled lansoprazole is actually detected in gastric neutrophils. The oxidative burst of purified human neutrophils was measured by luminol-dependent chemiluminescence (ChL). [3H]Lansoprazole uptake sites in human gastric mucosa were observed by autoradiography. The magnitude of neutrophil infiltration of gastric mucosa was assessed by tissue myeloperoxidase (MPO) content. ChL assay indicated that oxygen-derived free radical production was increased twofold by adding H. pylori water extract, which was significantly inhibited by lansoprazole (10(-4) M). Gastric biopsy samples were obtained endoscopically from patients with H. pylori-positive gastritis. Autoradiographic examination revealed that the [3H]lansoprazole binding site was present in the cytoplasmic granules of infiltrated neutrophils. Tissue MPO content was significantly decreased after treatment with lansoprazole. These data suggest that lansoprazole binds directly to neutrophils, subsequently inhibiting neutrophil accumulation and release of toxic metabolites.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7594353&dopt=Abstract lansoprazole Prevacid



Prevacid
Effect of anti-ulcer drugs on DNA synthesis in adult normal human hepatocytes in culture.

Blanc P, Liautard J, Greuet J, Daures JP, Fabre JM, Larrey D, Michel H, Maurel P.

INSERM U-128, CNRS, Montpellier, France.

The aim of this work was to investigate the effect of four H2 receptor antagonist, cimetidine, ranitidine, famotidine, nizatidine, and of two proton pump inhibitors, omeprazole and lansoprazole, on the mitotic response of human hepatocytes in primary culture. After plating at subconfluent density, cells were exposed to 0.2 to 20 mumol/L of these drugs for 48 hours, either in the absence or in the presence of epidermal growth factor (EGF). The rate of DNA synthesis was evaluated by [3H]-thymidine incorporation into genomic DNA. Both the basal rate of DNA synthesis and the extent of stimulation by EGF exhibited a wide interindividual variability, and were not correlated with the viability of freshly prepared cells. In contrast, the effects of anti-ulcer drugs on the rate of DNA synthesis were clearly reproducible from one culture to another. H2 receptor antagonists had no significant effect (P > .2) over the entire range of concentration tested, whereas omeprazole and lansoprazole significantly inhibited the rate of DNA synthesis by 60% to 90% at 30 mumol/L (P = .016). This effect was concentration dependent between 2 and 20 mumol/L. Neither of the drugs tested was cytotoxic under the conditions used in this work, as assessed by measurements of the do nov protein synthesis. We conclude that, in contrast to H2 receptor antagonists, omeprazole and lansoprazole are able to interfere with the replicative synthesis of DNA in human hepatocytes in culture, at suprapharmacological concentrations. Whether or not this effect is clinically significant remains to be established.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7657287&dopt=Abstract lansoprazole Prevacid