Prevacid
Antibacterial properties of lansoprazole alone and in combination with antimicrobial agents against Helicobacter pylori.

Nakao M.

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

The activities of various types of anti-ulcer agents against Helicobacter pylori (Hp) strains were determined using an agar dilution method. Among the compounds tested, proton pump inhibitors were found to exhibit significant activity against this organism. The activity of lansoprazole was four times more potent than that of omeprazole and bismuth subsalicylate, with MICs ranging from 1.56 to 25 micrograms/ml. Exposure of Hp to lansoprazole led to extensive loss of viability and suppression of virulence factors such as motility, adhesiveness to epithelial cells, and urease activity. Lansoprazole produced aberrant bacterial morphology characterized by elongation and constriction of the cells and collapse of cell surface structures. The combination of lansoprazole with antimicrobial agents such as penicillins, cephalosporins, macrolides, tetracyclines, aminoglycosides, quinolones, and metronidazole produced an additive or synergistic growth inhibition of Hp.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7673612&dopt=Abstract lansoprazole Prevacid



Prevacid
Evaluation of the effect of lansoprazole in suppressing acid secretion using 24-hour intragastric pH monitoring.

Takeda H, Hokari K, Asaka M.

Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.

The acid-inhibitory effect of lansoprazole was evaluated in comparison with that of famotidine and omeprazole by using 24-h intragastric pH monitoring in 10 young, healthy Japanese volunteers. Lansoprazole 20 mg once daily in the morning was superior to famotidine 20 mg twice daily, omeprazole 20 mg once daily in the morning in reducing 24-h intragastric acidity. Unlike famotidine, whose acid-inhibitory effect was observed mainly at night, both lansoprazole and omeprazole inhibited both daytime and nocturnal acid secretion, with the maximal effect occurring in the afternoon. Although the daily profile of acid-inhibitory action of lansoprazole was similar to that of omeprazole, the acid-inhibitory effect of lansoprazole was more potent than that of omeprazole at any time of the day. These results indicate that lansoprazole at a dosage of 30 mg once daily in the morning produced the most potent inhibition of acid secretion in young Japanese volunteers, compared with famotidine 20 mg twice daily and omeprazole 20 mg once in the morning.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7673616&dopt=Abstract lansoprazole Prevacid



Prevacid
Inhibitory action of lansoprazole and its analogs against Helicobacter pylori: inhibition of growth is not related to inhibition of urease.

Nagata K, Takagi E, Tsuda M, Nakazawa T, Satoh H, Nakao M, Okamura H, Tamura T.

Department of Bacteriology, Hyogo College of Medicine, Japan.

The proton pump inhibitors omeprazole and lansoprazole and its acid-activated derivative AG-2000, which are potent and specific inhibitors of urease of Helicobacter pylori (K. Nagata, H. Satoh, T. Iwahi, T. Shimoyama, and T. Tamura, Antimicrob. Agents Chemother. 37:769-774, 1993), inhibited the growth of H. pylori. The growth was inhibited not only in urease-positive clinical isolates but also in their urease-negative derivatives which had no urease polypeptides. AG-1789, a derivative of lansoprazole with no inhibitory activity against H. pylori urease, also inhibited the growth of both strains even more strongly than the urease inhibitors lansoprazole and AG-2000. Furthermore, the antibacterial activity of omeprazole and lansoprazole was not affected by glutathione or dithiothreitol, which completely abolished the inhibitory activity of lansoprazole against H. pylori urease. These results indicated that the inhibitory action of these compounds against the growth of H. pylori was independent from the inhibitory action against urease.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7726537&dopt=Abstract lansoprazole Prevacid



Prevacid
Uptake site of lansoprazole, a proton pump inhibitor, in human fundic mucosa: possible relevance with fibroblast and Helicobacter pylori.

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

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

To clarify the mechanism of the effect of lansoprazole in the healing of human gastric ulcer, the uptake sites of lansoprazole were studied using endoscopically biopsied specimens from the margin of the gastric ulcer. The specimens were incubated in a medium containing 3H-lansoprazole for 5 or 15 min., postfixed with 1% osmic acid and embedded in Epon. The semithin or ultrathin sections were made and radioautographic emulsion films were applied by the wire-loop method. 30 days after the incubation, the sections were developed, fixed and observed by light and electron microscopy. As a result, the uptake sites of lansoprazole were accumulated on the fibroblasts located near the tip portion of the gastric mucosa and on the unmyelinated nerve fibers as well as on the parietal cells. Some of the uptake sites were also observed near the plasma membrane of the bacteria in the gastric lumen. From these observations, lansoprazole uptake sites were not only on the parietal cells but on the fibroblasts and the bacteria, suggesting that the effect of lansoprazole was exerted partly through the influence on the mesenchymal cells and Helicobacter pylori-related organisms.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7773126&dopt=Abstract lansoprazole Prevacid



Prevacid
Specific proton pump inhibitors E3810 and lansoprazole affect the recovery process of gastric secretion in rats differently.

Tomiyama Y, Morii M, Takeguchi N.

Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.

After a single subcutaneous administration (30 mg/kg) of proton pump inhibitor 2-[(4-(3-methoxypropoxy)-3-methylpyridin-2-yl)-methylsulfiny l]- 1H-benzimidazole sodium salt (E3810), or lansoprazole in rats, time courses of inhibitory and recovery processes of acid secretion in vivo and pump enzyme activity in isolated microsomes were measured. The acid secretion rate which reflects H+,K(+)-ATPase activity in the secretory canalicular (apical) membrane was compared with that in the microsomal fraction which consists mostly of resting, intracellularly-pooled tubulovesicles. We found that the canalicular pump was first inhibited, followed by slow inhibition of the microsomal pump enzyme activity, with the rate of the latter process depending on the inhibitors. It took 2.5 hr for the half-maximal inhibition of the microsomal pump in E3810-treated rats, and 6 hr in lansoprazole-treated rats. The acid secretion and the microsomal enzyme activity completely recovered within 48 hr after the administration of E3810, but recovered by only 20% even 96 hr after the administration of lansoprazole. Incubation with dithiothreitol of isolated microsomes obtained from E3810-treated rats reactivated the enzyme activity, but not from rats treated with lansoprazole. These results suggest that dissociation of inhibitor from the pump and/or intracellular transport of the pump is affected differently by these inhibitors. Furthermore, it is possible that the half life of the proton pump protein is much longer (greater than 96 hr) than the previously proposed value of 30-48 hr.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7802694&dopt=Abstract lansoprazole Prevacid