Comparison of five antisecretory agents acting via gastric H+/K+-ATPase

Lansoprazole(L), pantoprazole (P), rabeprazole(R) and RO-18-5364 (RO) are n ew benzimidazole derivatives which rival omeprazole (O) as proton pump inhi bitors (PPIs) for treatment of ulcer disease. In this study, we compared th e effects of these compounds on acid secretion and determined their relativ e potencies in relation to their effect on [C-14]-aminopyrine (AP) accumula tion in isolated gastric glands. Inhibition of AP (1.2 mu Ci.mL(-1)) accumu lation was measured in rabbit isolated gastric glands. dbcAMP (1 mmol; stim ulant of acid secretion) and Ro 20-1724 (0.1 mmol; a phosphodiasterase inhi bitor) were added to the Eppendorf tubes containing the PPIs and AP and dos e-response curves were done for each drug after incubating for 5, 10 and 20 min at 37 degrees C and AP accumulation was determined using a scintillati on counter. All the PPIs significantly (P < 0.001) inhibited acid secretion as demonstrated by the inhibition of AP accumulation in the isolated gastr ic glands. Minimum inhibition occurred at a concentration of 0.001 mu mol f or lansoprazole and omeprazole, 0.01 mu mol for rabeprazole and RO 18-5364 and 0.02 mu mol for pantoprazole. No differences were observed between PPIs with regards to the maximum inhibition they produce. When expressed as a p ercentage inhibition of control at 10-min incubation and at concentrations of 1 mu mol, L showed 85.6 +/- 0.5, O 87 +/- 0.5, P 83.2 +/- 1.1, R 86.4 +/ - 1.1 and RO 87.8 +/- 1.9 inhibition respectively When comparing the IC,, v alues, their relative potencies were different. Maximum potency was shown b y L (0.007 mu mol) > O (0.012 mu mol) > R (0.018 mu mol) > RO (0.034 mu mol ) > P (0.050 mu mol). All the new PPIs showed different potencies as inhibi tors of acid secretion as evident from their IC(50)s. Extensive ulcer heali ng trials demonstrated comparable efficacy with a number of studies indicat ing that symptoms relief are more rapid with P and L, while in this study L appeared to be the most potent in inhibiting AP accumulation in the isolat ed gastric glands. O 2000 Elsevier Science Ltd. Published by conditions sci entifiques et medicales Elsevier SAS.