Interaction of drugs for eradication therapy against antibiotic-resistant strains of Helicobacter pylori. 2-[(2-pyridylmethyl)sulfinyl]-1H-thieno[3,4-d]imidazoles. A novel class of gastric H+/K(+)-ATPase inhibitors. Relationship between the eradication of Helicobacter pylori and the healing pattern of peptic ulcer. Rx drugs

Drugs online research references

Microbiol Immunol. 1997;41(11):865-9.
Interaction of drugs for eradication therapy against antibiotic-resistant strains of Helicobacter pylori.

Gotoh A, Kawakami Y, Akamatsu T, Katsuyama T.

2nd Department of Internal Medicine, Shinshu University School of Medicine, Nagano, Japan.

To clarify the interactions of drugs for combination therapy of Helicobacter pylori infection, especially due to antibiotic-resistant strains, we have evaluated the in vitro effect of combining different drugs. Using a modified time-kill assay, we tested the effect of combining 2 drugs from 4 agents; amoxicillin (AMPC), clarithromycin (CAM), metronidazole (MTZ) and lansoprazole (a proton pump inhibitor). The H. pylori in the study consisted of 4 strains sensitive to the all drugs, 2 strains resistant only to CAM, 2 strains resistant only to MTZ, and 2 strains resistant to both CAM and MTZ. From the 6 different drug combinations, synergism was observed for 5 of the combinations, among which the combination of AMPC and CAM revealed such effects most frequently. However, all of the strains which showed synergism were sensitive to both of the drugs. In the case of the strains resistant to CAM and/or MTZ, no synergism was demonstrated in any of the combinations including CAM and/or MTZ. When a strain was resistant to one drug from a combination, no synergism was detected. Thus, the administration of a drug to which the strains are resistant may have no advantage in the eradication therapy of H. pylori. For a more effective and safer therapy, susceptibility testing should be performed before treatment.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9444328&dopt=Abstract

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J Med Chem. 1992 Feb 7;35(3):438-50.
2-[(2-pyridylmethyl)sulfinyl]-1H-thieno[3,4-d]imidazoles. A novel class of gastric H+/K(+)-ATPase inhibitors.

Weidmann K, Herling AW, Lang HJ, Scheunemann KH, Rippel R, Nimmesgern H, Scholl T, Bickel M, Metzger H.

Hoechst AG, Pharma Research, Frankfurt, Germany.

2-[(2-Pyridylmethyl)sulfinyl]thienoimidazoles were synthesized and investigated as potential inhibitors of gastric H+/K(+)-ATPase. The [3,4-d] isomers of the two possible thienoimidazole series were found to be potent inhibitors of gastric acid secretion in vitro and in vivo. Structure-activity relationships indicate that especially lipophilic alkoxy, benzyloxy, and phenoxy substituents with additional electron-demanding properties in the 4-position of the pyridine moiety combined with an unsubstituted thieno[3,4-d]imidazole lead to highly active compounds with a favorable chemical stability. Various substitution patterns in the thieno[3,4-d]imidazole moiety result in lower biological activity. The heptafluorobutyloxy derivative saviprazole (HOE 731, 5d) was selected for further development and is currently undergoing clinical evaluation. Comprehensive pharmacological studies indicate a pharmacodynamic profile different to omeprazole, the first H+/K(+)-ATPase blocker introduced on the market.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1310742&dopt=Abstract

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J Clin Gastroenterol. 1998;27 Suppl 1:S159-62.
Relationship between the eradication of Helicobacter pylori and the healing pattern of peptic ulcer.

Suzuki J, Mine T, Kobayasi I, Fujita T.

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

We investigated the relationship between the eradication of Helicobacter pylori and the stage after the eradication of this bacterium. Eighty-six patients with H. pylori who had gastric ulcer (n=45) or duodenal ulcer (n=41) were enrolled in the study. As eradication therapy, patients received 1,500 mg amoxicillin, 400 mg clarithromycin, and 30 mg lansoprazole for 2 weeks, followed by 30 mg lansoprazole for 6 weeks in patients with gastric ulcer or for 4 weeks in those with duodenal ulcer. The ulcer stages were evaluated using the indigocarmine method at the third and sixth month after entry. The overall eradication rate of H. pylori was 85% in this study. In the gastric ulcer group, 62% of H. pylori-eradicated patients and 37.5% of H. pylori-uneradicated patients showed the S2 stage (white scar) at the sixth month. In the duodenal ulcer group, 61% of H. pylori-eradicated patients showed the S2 stage and none of the H. pylori-uneradicated patients showed the S2 stage (p < 0.05). We concluded that H. pylori eradication might promote not ulcer healing but maturity of the ulcer scar, especially in duodenal ulcer patients, and that this might also be related to the reduction of ulcer relapse.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9872515&dopt=Abstract

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