Is the Time of Dosing of a Potent Long-Acting H₂-Receptor Antagonist Critical? Twenty-Four-Hour pH Measurements with SKF-94482

Abstract

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) were 2.6 (2.2-3.2), 2.3 (2.1-3.8), and 2.6 (1.8-3.6), respectively. When the time of dosing was 1830 h with 400 mg SKF-94482, median 24-h, day and night pH were 3.4 (2.5-4.0), 3.4 (3.1-4.3), and 3.7 (2.8-5.9), respectively. Early-evening dosing of this long-acting H_& antagonist resulted in substantially greater suppression of intragastric acidity than morning dosing.

Key Words:

• Dosing
• H₂-blockers
• pharmacodynamics
• 24-h pH-metry