Omeprazole cycle

Scheme 2.2 Mechanism for the transformation of omeprazole in acid. Formation of the active sulfenamide (or, alternatively, the sulfenic acid), the inhibitory reaction with the enzyme and cleavage of the enzyme-inhibitor complex by mercaptan (the omeprazole cycle ).

The last step in the omeprazole cycle (Scheme 1.2) finds support in the fact that the sulfide S is formed from omeprazole A in isolated gastric glands and in... 

They are both pro-drugs and their MOA is through the omeprazole cycle, initiated by pyridine s lone pair of electrons. In fact, pyridine s lone pair of electrons could be viewed as the engine that propels the omeprazole cycle. The pyridinium sulfydryl intermediate is the actual inhibitory species. 

Refer to Section 3.6. Chiral drugs are more effective than racemic mixtures as they can better interact with active sites to alter disease progression. An important example is the case of omeprazole and esomeprazole (Exhibit 3.16). It is also strategically important for pharmaceutical companies to work on chiral drugs to further the product life cycle and compete with generics. 

Berkowitz BA, Sachs G Life cycle of a block buster Discovery and development of omeprazole (Prilosec ). Mol Interv 2002 2 6. [PMID 14993356]... 

Frerichs et al. [128] developed and validated a method for the quantitation of omeprazole and hydroxyomeprazole from one 250 [A sample of human plasma using HPLC coupled to tandem mass spectrometry. The method was validated for a daily working range of 0.4-100 ng/ml, with limits of detection between 2 and 15 pg/ml. The interassay variation was less than 15% for all analytes at four control concentrations and the samples were stable for three freeze-thaw cycles under the analysis conditions and 24 h in the postpreparative analysis matrix. The method was used to analyze samples in support of clinical studies probing the activity of the cytochrome P-450 enzyme system. 

Kim MJ, Bertino JS, Jr., Gaedigk A, Zhang Y, Sellers EM, Nafziger AN. Effect of sex and menstrual cycle phase on cytochrome P450 2C19 activity with omeprazole used as a biomarker. Clin Pharmacol Ther 2002 72 192-9. 

Two molecules of the active intermediate of omeprazole bind to one active site of gastric H /K -ATPase [63, 64], This binding is a disulphide linkage and can be prevented and reversed by the addition of mercaptan [65-67]. Detailed investigations of three reactions of H /K -ATPase enzyme cycle have shown that the K -stimulated ATPase-activity, / -nitrophenol-phosphatase(pNPPase)-activity and formation of phosphoenzyme are also inhibited [63, 68]... 

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