title: Comparison of five antisecretory agents acting via gastric H+/K+-ATPase.
abstract: Lansoprazole(L), pantoprazole (P), rabeprazole and RO-18-5364 (RO) are new benzimidazole derivatives which rival omeprazole (O) as proton pump inhibitors (PPIs) for treatment of ulcer disease. In this study, we compared the effects of these compounds on acid secretion and determined their relative potencies in relation to their effect on [14C]-aminopyrine (AP) accumulation in isolated gastric glands. Inhibition of AP (1.2 microCi x mL(-1)) accumulation was measured in rabbit isolated gastric glands. dbcAMP (1 mmol; stimulant of acid secretion) and Ro 20-1724 (0.1 mmol; a phosphodiasterase inhibitor) were added to the Eppendorf tubes containing the PPIs and AP and dose-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 scintillation counter. All the PPIs significantly (P < 0.001) inhibited acid secretion as demonstrated by the inhibition of AP accumulation in the isolated gastric glands. Minimum inhibition occurred at a concentration of 0.001 micromol for lansoprazole and omeprazole, 0.01 micromol for rabeprazole and RO 18-5364 and 0.02 micromol for pantoprazole. No differences were observed between PPIs with regards to the maximum inhibition they produce. When expressed as a percentage inhibition of control at 10-min incubation and at concentrations of 1 micromol, 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 IC50 values, their relative potencies were different. Maximum potency was shown by L (0.007 micromol) > O (0.012 micromol) > R (0.018 micromol) > RO (0.034 micromol) > P (0.050 micromol). All the new PPIs showed different potencies as inhibitors of acid secretion as evident from their IC50s. Extensive ulcer healing trials demonstrated comparable efficacy with a number of studies indicating 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 isolated gastric glands.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, UAE University, Al Ain.
authors.forename: S M
authors.initials: SM
authors.lastname: Bastaki
authors.forename: I
authors.initials: I
authors.lastname: Chandranath
authors.forename: A
authors.initials: A
authors.lastname: Garner
mesh_terms: D000632:Aminopyrine / Q000493:pharmacokinetics; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism*; D066298:In Vitro Techniques; D009853:Omeprazole / Q000494:pharmacology; D011817:Rabbits; D013270:Stomach / Q000201:enzymology*
chemical_list: D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D000632:Aminopyrine; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole