Drugs online research references
Nippon Rinsho. 1992 Jan;50(1):11-7.
[Discovery and development of the proton pump inhibitor]
[Article in Japanese]
Igata H, Okabe S.
Department of Applied Pharmacology, Kyoto Pharmaceutical University.
Gastric (H+/K+)-ATPase, the proton pump of the parietal cell, is responsible for the final step of acid secretion in the stomach. In 1981, picoprazole, a substituted benzimidazole, was found to inhibit (H+/K+)-ATPase. It was reported in 1983 that omeprazole has the most potent efficacy among the substituted benzimidazoles and today, omeprazole has been used for treatment of gastroduodenal disease. Recently, lansoprazole, similar to omeprazole in chemical structure, was developed in Japan, and several other compounds, such as pantoprazole, E-3810 and NC-1300-O-3, have also been reported to suppress acid secretion through inhibition of (H+/K+)-ATPase. In the present paper the background of the discovery of (H+/K+)-ATPase and development of proton pump inhibitors is reviewed.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1311779&dopt=Abstract
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J Chromatogr. 1992 Sep 2;579(2):299-305.
Simultaneous determination of omeprazole and its metabolites in plasma and urine by reversed-phase high-performance liquid chromatography with an alkaline-resistant polymer-coated C18 column.
Kobayashi K, Chiba K, Sohn DR, Kato Y, Ishizaki T.
Division of Clinical Pharmacology, National Medical Center, Tokyo, Japan.
Omeprazole (OPZ) is a proton pump inhibitor in gastric parietal cells. A reversed-phase high-performance liquid chromatographic method was developed that enables concentrations of OPZ and its major metabolites, omeprazole sulphone (OPZ-SFN) and hydroxy-omeprazole (H-OPZ), to be determined simultaneously in plasma and that of H-OPZ in urine. To prevent decomposition of OPZ, all the processes (extraction, injection and elution) were carried out under alkaline conditions. Recoveries of the analytes and internal standard were greater than 93.1%. The intra- and inter-assay coefficients of variation were less than 9.1 and 6.4% for plasma samples and less than 2.9 and 3.9% for urine samples, respectively. The minimum determinable concentration (relative standard deviation 10-15%) was 10 ng/ml for all analytes in plasma and H-OPZ in urine samples. The clinical applicability of this assay method was evaluated by determining plasma concentration-and urinary excretion-time courses of the respective analyte(s) in four healthy volunteers after an oral dose of 20 mg of OPZ. The present assay is considered to be simple, precise and accurate and suitable for the study of the kinetic disposition and metabolism of OPZ, which is an extensively metabolized drug in the human liver.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1429977&dopt=Abstract
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Scand J Gastroenterol. 1992 Oct;27(10):875-83.
Stereologic investigations of human gastric mucosa. II. Oxyntic mucosa from patients with Zollinger-Ellison syndrome.
Helander HF, Rutgersson K, Helander KG, Pisegna JP, Gardner JD, Jensen RT, Maton PN.
Dept. of Cell Biology, AB Astra Hasle, Molndal, Sweden.
Biopsy specimens from the oxyntic mucosa were obtained on 210 occasions from 76 patients with the Zollinger-Ellison syndrome (ZES) before and during omeprazole treatment. One-micrometer sections were examined by light microscopy, and in 5% linear hyperplasia of endocrine cells was observed. Morphometry was carried out in 91 of the specimens and showed a significant increase of the mean endocrine cell density in comparison with both young, healthy subjects and patients suffering from active peptic ulcer disease (PUD). No metaplasia, dysplasia, or neoplasia was detected in patients with ZES, and the mean mucosal thickness and parietal cell density remained normal. The parietal cells often displayed endosome-like structures, and occasionally there were lingulate cytoplasmic projections into the gland lumen. Electron microscopic morphometry was carried out in specimens from nine patients with ZES and did not show any significant differences in the parietal cells in comparison with healthy subjects.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1439541&dopt=Abstract
note: kwd match prilosec online literature
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