Pantoprazole sodium is a substituted benzimidazole derivative which control
s acid secretion by inhibition of gastric H+/K+-ATPase. The prodrug pantopr
azole accumulates in the acidic space of the parietal cell where it is conv
erted to the pharmacologically active principle, a thiophilic cyclic sulfen
amide. The pH-dependent activation profile, i.e., activation at pH I versus
activation at pH 4-6, is more favorable for pantoprazole than for the othe
r proton pump inhibitors (PPIs) currently available. In vitro, pantoprazole
interferes less potently than omeprazole with biological targets not relat
ed to gastric acid secretion. The gastric target sites for the pantoprazole
sulfenamide are the cysteines 813 and 822 of the catalytic subunit of the
H+/K(+)ATPase. In contrast to omeprazole, the two binding sites are located
right at the proton channel. In rats, dogs and humans, pantoprazole produc
es marked and prolonged inhibition of both basal and stimulated acid secret
ion. Overall, its antisecretory potency is equal to that of omeprazole. Ant
iulcer activity has been demonstrated for pantoprazole in two rat models. A
s seen with H-2-receptor antagonists and other PPIs, pantoprazole causes an
increase in serum gastrin concentration which reflects the degree of gastr
ic acid inhibition. Pantoprazole is mainly metabolized by CYP3A4 and 2C19,
but displays a lower affinity for these phase I cytochrome P450 enzymes tha
n omeprazole. In contrast to the latter, pantoprazole is further conjugated
with sulfate by the hepatic phase II metabolism. These two differences may
explain why pantoprazole does not interfere with the metabolism of any oth
er drug thus far tested in humans. (C) 1999 Prous Science. All rights resen
ted.