Prazol - Omeprazole

Proton pump inhibitors -prazole Omeprazole, lansoprazole Gastric ulcers (27)... 

Rezk et al. [74] developed and validated a reversed-phase HPLC assay method for the simultaneous quantitative determination of omeprazole and its three metabolites in human plasma. The method provides excellent chromatographic resolution and peak shape for the four components and the internal standard within a 17-min run time. The simple extraction method results in a clean baseline and relatively high extraction efficiency. The method was validated over the range of 2-2000 ng/ml. The resolution and analysis for the four analytes omeprazole, hydroxyome-prazole, omeprazole sulfone, and omeprazole sulfide and the internal standard utilized a Zorbax C18 (15 cm x 3 mm, 5 /im) with a Zorbax C18 (12.5 cm x 4.6 mm) guard column. The mobile phase consisted of two components. Mobile phase A was 22 mM phosphate monobasic, adjusted to a pH of 6 with diluted sodium hydroxide. This solution was filtered through a 0.45-/im membrane filter, then mixed as 900 ml buffer to 100 ml methanol. Mobile phase B was composed of 100 ml of the phosphate buffer as mobile phase A, mixed with 800 ml of acetonitrile, 100 ml of methanol, and 100 /A of trifluoroacetic acid with an initial flow-rate of 0.55 ml/min and detection at 302 nm. 

The anti-ulcer agents omeprazole, lanzoprazole, and pantoprazole have been introduced during the past decade for the treatment of peptic ulcers. Gastric acid secretion is efficiently reduced by prazole inhibition of H+K+-ATPase in the parietal cells of the gastrointestinal mucosa [75]. The prazoles themselves are not active inhibitors of the enzyme, but are transformed to cyclic sulfenamides in the intracellular acidic compartment of parietal cells [76]. The active inhibitors are permanent cations at pH < 4, with limited possibilities of leaving the parietal cells, and thus are retained and activated at the site of action. In the neutral body compartments the prazoles are stable, and only trace amounts are converted to the active drugs. (For a review on omeprazole, see Ref. [77].)... 

The PPIs are metabolized to inactive metabolites [5]. Omeprazole s dominant metabolite, 5-hydroxyome-prazole is formed via CYP2C19 metaboUsm, but there is also a minor component metabolized via CYP3A4 forming an omeprazole sulphone. Both are subsequently metabolized to omeprazole hydroxysulphone. 

Welage LS, Berardi RR. Evaluation of omeprazole, lansoprazole, panto-prazole, and rabeprazole in the treatment of acid-related disorders. J Am Pharm Assoc 2000 40 52-62. 

Omeprazole and related -prazoles are irreversible, direct inhibitors of the proton pump (K+/H+ antiporter) in the gastric parietal cell (see Figure VI-1 -1). 

Omeprazole and the other prazole" proton-pump inhibitors are more powerful inhibitors of gastric i secretion than the antagonists. Their clinical uses and adverse reactions are considered. 

Omeprazole and related -prazoles are irreversible, direct inhibitors of the proton... 

Omeprazole and other members of the prazole family irreversibly inhibit the proton pump. The answer is (D). 

A study in epileptic patients found that omeprazole 20 mg daily did not affect the serum levels of phenytoin, whereas earlier studies in healthy subjects su ested that phenytoin levels might be modestly raised by omeprazole 40 mg daily. A study with esome-prazole also suggests it may cause a minor rise in phenytoin levels. Lansoprazole does not normally affect phenytoin levels, but an isolated case report of toxicity is tentatively attributed to an interaction. Pantoprazole and rabeprazole appear not to interact. 

Clarithromycin approximately doubles the serum levels of esomeprazole, lansoprazole and omeprazole, but has no effect on panto-prazole. A small rise in the serum levels of clarithromycin might also occur, which may be therapeutically useful. Some very limited evidence indicates that erythromycin raises serum omeprazole... 

Two very different approaches to inhibition of the H, K -ATPase exist today. By far the most well documented class of compounds is that of the substituted pyxidinemethylsulphinylbenzimidazoles. These compounds covalently inhibit H, K -ATPase, which means that the pump is inhibited in an irreversible manner. Omeprazole, pantoprazole, lansoprazole, rabe-prazole and others (see Fig. 1) belong to this class of agents. 

References will mainly be made to omeprazole, the first and most widely documented PPI developed and used in the clinic. In most cases findings have been described and confirmed in studies with lanzoprazole and panto-prazole. Notes about the corresponding findings can be found in prescribing information and investigators brochures for these products, but there are few publications in the literature. 

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