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Repeated pentagastrin-stimulated gastric acid secretory tests carried out in the evaluation of the pharmacodynamics of a new histamine H2-receptor antagonist, SK&F 93479.

Single doses of 10 mg or 20 mg intravenously or 25 mg or 40 mg orally of a new histamine H2-receptor antagonist, SK&F 93479, have been administered to 31 patients with peptic ulcer disease. BAO and MAO were measured before and repeated during a 26-h period after drug administration. In a separate group of 17 patients the mean coefficients of variation of BAO and MAO measured in this manner were 53% and 20%, respectively. If this variation in the placebo group is taken into account, BAO was significantly inhibited at all dose levels during the 3rd h after dosing, and a significant effect was still seen during the 25th h after 40 mg orally with a mean reduction of 77%. Mean inhibitions of MAO during the 4th h after dosing of SK&F 93479 were significant at all dose levels, and a significant effect could still be seen during the 26th h for the two oral doses. The mean inhibitions of MAO measured during the 4th and 10th h after dosing were after 10 mg intravenously 44% and 11%, after 20 mg intravenously 59% and 11%, after 25 mg orally 57% and 21%, and after 40 mg orally 75% and 46%. The percentage inhibition of MAO during the 10th h correlated with plasma concentrations (r = 0.64, p less than 0.01). SK&F 93479 is a potent inhibitor of acid secretion with a long duration of action.