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) 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 H2 antagonist resulted in substantially greater suppression of intragastric acidity than morning dosing.
Wilder-Smith
C H
CH
Dept. of Medicine, University of Berne, Inselspital, Switzerland.
Merki
H S
HS
D000284:Administration, Oral; D000328:Adult; D004311:Double-Blind Method; D005502:Food; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D006635:Histamine H2 Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008991:Monitoring, Physiologic; D010880:Piperidines / Q000008:administration & dosage* / Q000494:pharmacology; D013997:Time Factors
D006635:Histamine H2 Antagonists; D010880:Piperidines; C052576:BMY 25368