Omeprazole and esomeprazole

AstraZeneca launched omeprazole in 1988. It is a safe and effective drug for acid reflux, functioning as a proton pump inhibitor. However, the patent has expired and AstraZeneca has to compete against generics. The company developed the active isomer and called it esomeprazole. It was approved by the Mutual Recognition process in Europe in July 2000, and by the US Food and Drug Administration in February 2001. The chemical formulas for omeprazole and esomeprazole are shown below. 

Omeprazole and esomeprazole. The two S atoms are chiral centers. Source Agranat I, Caner H, Caldwell J. Putting chirality to work the strategy of chiral switches of drug molecules, Nature Reviews Drug Discovery 1 753-768 (2002). Used with permission.)... 

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. 

Olbe L, Carlsson E, Lindberg P. A proton-pump inhibitor expedition the case histories of omeprazole and esomeprazole. Nat Rev Drug Discov 2003 2 132-9. 

Gastritis Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated long-term with omeprazole and esomeprazole. 

Fluconazole and voriconazole almost certainly cause a rise in omeprazole and esomeprazole levels by inhibiting their metabolism by the cytochrome P450 isoenzymes CYP2C19 and CYP3A4. As esomeprazole is an inhibitor of and also a substrate for CYP2C19, it is likely to have the same effect as omeprazole. Ketoconazole only inhibits CYP3A4 and therefore causes a less marked rise in omeprazole levels. Itraconazole would be expected to interact similarly to ketoconazole. 

Omeprazole and esomeprazole are also inhibitors of CYP2C19, and therefore they may increase the levels of drugs that are metabolised by CYP2C19, such as diazepam. Other CYP2C19 substrates are listed in Table 1.3 , (p.6).h Particular care may be required when giving drugs that... 

Wilcox GM, Mattia AR. Microscopic coh-tis associated with omeprazole and esomeprazole exposure. J Chn Gastroenterol 2009 43 551-3. 

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