197 omeprazol

Pyridine A Oxides. Analgesic and antiinflammatory dmgs niflumic acid [4394-00-7] (68) and pranoprofen [52549-17-4] (69) are manufactured from nicotinic acid N-oxide [2398-81 -4]. The antiulcer dmg omeprazole (66) is produced from 2,3,5-trimethylpyridine N-oxide [74409-42-0]. Zinc pyrithione, the zinc salt of pyrithione (45), is a fungicide derived from 2-chloropyridine N-oxide (45). 

The discovery of the antiulcer activity of H2 antihistamine antagonists has revolutionized the treatment of that disease. A benzimidazole. Omeprazole (55), inhibits gastric secretion and subsequent ulcer formation by a quite different mechanism. Studies at the molecular level suggest that this compound inhibits K /H dependent ATPase and consequently shuts down the proton pumping action of this enzyme system. 

Treatment of pyridyl carbinol 51 with thionyl chloride leads to the corresponding chloride (52), Treatment of that intermediate with 5-methoxy-2-mercaptobenzimidazole (53), obtained from reaction of 4-methoxy-q-phenylenediamine with potassium ethylxanthate leads to displacement of halogen and formation of the sulfide (54). Finally, oxidation with 3-chloroperbenzoic acid produces the sulfoxide omeprazole (55) fl7]. 

Figure 11.5 Chromatograms of plasma samples obtained with fully automated on-line SPE-LC (a) dmg-ffee human plasma (b) human plasma spiked with omeprazole (100 ng/ml) and phenacetin (internal standard 1000 ng/ml). Reprinted from Journal of Pharmaceutical and Biomedical Analysis, 21, G. Garcia-Encina et al., Validation of an automated liquid chromatograpliic method for omeprazole in human plasma using on-line solid-phase exti action, pp. 371 - 382, copyright 1999, with permission from Elsevier Science.

Cytochrome P450 2C19, also termed S-mephenytoin hydroxylase, is a mixed-function oxidase localized in the endoplasmic reticulum which is responsible for the biotransformation of S-mephenytoin, some barbiturates, almost all proton pump inhibitors such as omeprazole, diazepam and others. 

C8 C9 C18 C19 C58P C62P Taxol (C8), NSAIDS, warfarin (C9), omeprazole (C19)... 

Cytochrome P450 2C19 Deficient activity in about 3% of Caucasian populations and in about 20% of Asian populations. Prolonged action of several CYP2C19 inactivated drugs like omeprazole or diazepam in the poor metabolizers. 

The first compound of this class with inhibitory activity on the enzyme and on acid secretion was the 2-(pyridylmethyl)sulfinylbenzimidazole, timopra-zole, and the fust pump inhibitor used clinically was omeprazole, 2-[[3,5-dimethyl-4-methoxypyridin-2-yl] methylsulfinyl]-5-methoxy- lH-benzimidazole. Omeprazole is an acid-activated prodrug. Omeprazole and the other PPIs are accumulated in the acidic space of the parietal cell due to the pKa of the pyridine nitrogen and these are converted due to protonation of the benzimidazole nitrogen first to a thiol-reactive cationic sulfenic acid and then dehydrated to form the sulfenamide (Fig. 1). These thiophilic cations then bind to luminally... 

Substituted benzimidazole inhibitors show slightly different effects depending on the inhibitor structure. Omeprazole binds to cysteines in the extracytoplasmic regions of M5/M6 (cys-813) and M7/M8 (cys-892). 

Abelo A, Andersson TB, Antonsson M et al (2000) Stereoselective metabolism of omeprazole by human cytochrome P450 enzymes. Drug Metab Dispos 28 966-972... 

Dofetilide is not administered with cimetidine because dofetilide plasma levels may be increased by as much as 50%. When treatment for gastric disorders is necessary, patients receiving dofetilide should take omeprazole ranitidine, or antacids as an alternative to cimetidine. 

The proton pump inhibitors are contraindicated in patients who have hypersensitivity to any of the drags. Omeprazole (Pregnancy Category C) and lansoprazole, rabeprazole, and pantoprazole (Pregnancy Category B) are contraindicated during pregnancy and lactation. The proton pump inhibitors are used cautiously in older adults and in patients with hepatic impairment. 

Omeprazole—Swallow tablets whole do not chew them. This drug will be taken for up to 8 weeks or for a prolonged period. Regular medical check-ups are required. 

C3H5KOS2 140-89-6) see Cefaclor Omeprazole Pantoprazole sodium Protizinic acid Pyritinol potassium hexachloroplatinate(IV)... 

---