Endoscopic characteristics of low-grade gastric mucosa-associated lymphoid tissue lymphoma after eradication of Helicobacter pylori. Pharmacological properties of a newly synthesized H(+)/K(+) ATPase inhibitor, 1-(2-methyl-4-methoxyphenyl)-4-. Rx drugs

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This study demonstrates the stereoselective metabolism of the optical isomers of omeprazole in human liver microsomes. The intrinsic clearance (CL(int)) of the formation of the hydroxy metabolite from S-omeprazole was 10-fold lower than that from R-omeprazole. However, the CL(int) value for the sulfone and 5-O-desmethyl metabolites from S-omeprazole was higher than that from R-omeprazole. The sum of the CL(int) of the formation of all three metabolites was 14.6 and 42.5 microl/min/mg protein for S- and R-omeprazole, respectively. This indicates that S-omeprazole is cleared more slowly than R-omeprazole in vivo. The stereoselective metabolism of the optical isomers is mediated primarily by cytochrome P450 (CYP) 2C19, as indicated by studies using cDNA-expressed enzymes. This is the result of a considerably higher CL(int) of the 5-hydroxy metabolite formation for R- than for S-omeprazole. For S-omeprazole, CYP2C19 is more important for 5-O-desmethyl formation than for 5-hydroxylation. Predictions of the CL(int) using data from cDNA-expressed enzymes suggest that CYP2C19 is responsible for 40 and 87% of the total CL(int) of S- and R-omeprazole, respectively, in human liver microsomes. According to experiments using cDNA-expressed enzymes, the sulfoxidation of both optical isomers is metabolized by a single isoform, CYP3A4. The CL(int) of the sulfone formation by CYP3A4 is 10-fold higher for S-omeprazole than for R-omeprazole, which may contribute to their stereoselective disposition. The results of this study show that both CYP2C19 and CYP3A4 exhibit a stereoselective metabolism of omeprazole. CYP2C19 favors 5-hydroxylation of the pyridine group of R-omeprazole, whereas the same enzyme mainly 5-O-demethylates S-omeprazole in the benzimidazole group. Sulfoxidation mediated by CYP3A4 highly favors the S-form.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10901708&dopt=Abstract

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J Gastroenterol Hepatol. 2000 Oct;15(10):1113-9.
Endoscopic characteristics of low-grade gastric mucosa-associated lymphoid tissue lymphoma after eradication of Helicobacter pylori.

Urakami Y, Sano T, Begum S, Endo H, Kawamata H, Oki Y.

Department of Gastroenterology, Urakami Gastroenterology Clinic, Tokushima, Japan.

BACKGROUND AND AIMS: It was recently reported that low-grade gastric lymphoma of mucosa-associated lymphoid tissue (MALT) was regressed by the eradication of Helicobacter pylori. The aim of this study was to confirm the effect of H. pylori eradication on low-grade gastric MALT lymphoma and to investigate the whitish mucosa that appeared with regression of the lesions. METHODS: Forty-seven H. pylori-positive patients with low-grade gastric MALT lymphoma were treated by using triple therapy. Biopsy specimens were histologically graded and B cell clonality was examined by using reverse transcription-polymerase chain reaction before and after eradication treatment. The relationship between the appearance of whitish mucosa and the degree of gastric gland loss was evaluated. RESULTS: Histologic regression was observed 2 months after eradication therapy in 42 of 47 patients. However, B cell monoclonality changed to polyclonality in only 23 patients during the follow-up period. The appearance of whitish mucosa in patients who showed histologic regression became more frequent as the degree of gastric gland loss increased (P< 0.001). CONCLUSIONS: Most low-grade gastric MALT lymphoma histologically regressed after H. pylori eradication. The appearance of whitish mucosa after histologic regression reflected the degree of gastric gland loss. Whitish mucosa is an endoscopic characteristic and may be an endoscopic marker for regression of low-grade gastric MALT lymphoma.

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Eur J Pharmacol. 2001 Jan 5;411(1-2):187-192.
Pharmacological properties of a newly synthesized H(+)/K(+) ATPase inhibitor, 1-(2-methyl-4-methoxyphenyl)-4-.

Cheon HG, Lee SS, Lim H, Lee DH.

Pharmaceutical Screening Center, Korea Research Institute of Chemical Technology, 100 Jang-Dong, Yusong-Gu, 305-343, Taejon, South Korea

A new compound, 1-(2-methyl-4-methoxyphenyl)-4-[(3-hydroxypropyl)amino]-6-methyl-2,3-dihydropyrrolo[3,2-c]quinoline (DBM-819), given intraduodenally in pylorus-ligated rats, inhibited basal acid secretion with an ED(50) value of 3.5 mg/kg. In addition, DBM-819 reduced histamine- and pentagastrin-stimulated gastric acid secretion with ED(50) values of 4.0 and 5.1 mg/kg, respectively. The duration of the anti-secretory effect was approximately 18 h when DBM-819 was administered orally to rats with a chronic gastric fistula. Oral administration of DBM-819 protected against gastric lesions induced by ethanol, NaOH, indomethacin and aspirin, and the duodenal ulcer induced by cysteamine, in a dose-dependent manner with ED(50) values of 7.0, 20, 3.1, 4.0 and 6.0 mg/kg, respectively. Taken together, these results suggest that DBM-819 acts as an effective oral anti-ulcer agent in vivo, and that DBM-819 could be developed as a new therapeutic agent for peptic ulcer disease.

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