Similarities and differences in the properties of substituted benzimidazoles: a comparison between pantoprazole and related compounds.
The novel antiulcer drugs omeprazole, lansoprazole, and pantoprazole are members of the class of substituted benzimidazoles. They potently inhibit the gastric proton pump by a common mechanism which depends on the acid-induced conversion of the parent compounds to the pharmacologically active principles: thiophilic cyclic sulfenamides. This transformation takes place in the luminal compartment of the secreting parietal cell. However, while the three proton pump inhibitors belong to the same chemical class, their two ring systems bear different functional substituents. This leads to essential modification of the physiochemical, metabolic, and pharmacokinetic properties of these drugs, possibly resulting in differences in tissue selectivity and thereby, in the long term, drug safety. Both preclinical and clinical data have accumulated that point to advantages of pantoprazole related to the above parameters: pantoprazole shows a higher stability at moderately acidic pH values and less inhibitory potential against cytochrome P450 than the other two drugs. In addition, pantoprazole displays linear pharmacokinetics with a high bioavailability.
Department of Pharmacology, Byk Gulden, Konstanz, Germany.
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D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D005744:Gastric Acid / Q000378:metabolism; D006801:Humans; D064747:Lansoprazole; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077402:Pantoprazole; D013454:Sulfoxides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D065607:Cytochrome P-450 Enzyme Inhibitors; D013454:Sulfoxides; D064747:Lansoprazole; D000077402:Pantoprazole; D009853:Omeprazole