Is the time of dosing of a potent long-acting H2-receptor antagonist critical? Twenty-four-hour pH measurements with SKF-94482.

Reduction of daytime as well as nighttime acidity is important in the healing of duodenal ulceration and reflux oesophagitis. The importance of the time of dosing of potent, long-acting H2 blockers for optimal suppression of intragastric acidity is unknown. The efficacy of different oral dosage regimens of SKF-94482, a new, competitive and long-acting H2-receptor antagonist, in reducing daytime and nighttime intragastric acidity was studied with 24-h pH-monitoring in 3 double-blind, randomized, crossover trials in 45 fed, healthy subjects. In study A 200 mg, 400 mg, or 600 mg SKF-94482 or placebo was given at 0830 h for 6 days. In study B the above doses were taken at 1830 h. In study C 200 mg or 300 mg of SKF-94482 or placebo was given at 0830 and 1830 h for 6 days. SKF-94482, 400 mg, was the most effective dose, and twice daily dosing was of no additional pharmacodynamic benefit. When 400 mg SKF-94482 was given at 0830 h, the median 24-h, day (0800-1800 h) and night (1800-0800 h) pH (interquartile range...