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

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...

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Bibliographic Details
Published in:Journal of physiology, Paris Paris, 2000, Vol.94 (1), p.19-23
Main Authors: Bastaki, Salim M.A., Chandranath, Irwin, Garner, Andrew
Format: Article
Language:English
Subjects:
[ 14C]-aminopyrine
Aminopyrine - pharmacokinetics
Animals
Anti-Ulcer Agents - pharmacology
Benzimidazoles - pharmacology
db cAMP
Enzyme Inhibitors - pharmacology
Gastric Acid - secretion
Gastric Mucosa - drug effects
Gastric Mucosa - metabolism
H(+)-K(+)-Exchanging ATPase - metabolism
In Vitro Techniques
lansoprazole
omeprazole
Omeprazole - pharmacology
pantoprazole
Rabbits
rabeprazole
RO 18-5364
RO 20-1724
scintillation solution
Stomach - enzymology
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Summary: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 μCi.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 °C and AP accumulation was determined using a scintillation counter. All the PPIs significantly ( P  O (0.012 μmol) > R (0.018 μmol) > RO (0.034 μmol) > P (0.050 μmol). All the new PPIs showed different potencies as inhibitors of acid secretion as evident from their IC 50s. 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.
ISSN:0928-4257
1769-7115
DOI:10.1016/S0928-4257(99)00108-4