Mepirizole (60 and 200 mg/kg) administered s.c. induced damage in the surface epithelial cells of the rat proximal duodenum as early
as 2 hr after the treatment. 16,16-Dimethyl
prostaglandin E2 (dmPGE2, 30 micrograms/kg) administered s.c. significantly protected the duodenal mucosa against
mepirizole-induced damage for up to 6 hr. Gastric acid secretion in acute
fistula preparations was significantly reduced 1 hr after administration of
mepirizole (60 and 200 mg/kg). The secretion reverted to the control level 2 hr later. In the 60 mg/kg-treated group, however, there was a significant increase in the
acid output for up to 6 hr. Duodenal HCO3- secretion, stimulated with 10 mM HCl was significantly inhibited with
mepirizole (60 and 200 mg/kg).
Mepirizole (60 and 200 mg/kg) significantly increased the amount of
acid in the duodenum for 2 to 6 hr after the treatment. dmPGE2 (30 micrograms/kg) significantly inhibited gastric acid secretion, stimulated duodenal HCO3- secretion, and reduced the increased amount of
acid in the duodenum in response to
mepirizole. Endogenous
prostaglandin E2 and 6-keto
prostaglandin F1 alpha in the duodenal mucosa were significantly reduced by
mepirizole (200 mg/kg) 1 to 2 hr later.
Mepirizole-induced duodenal damage appears to be caused by the increased amount of
acid in the duodenum.