The effects of roxatidine acetate (HOE-760) on 24-hour intragastric acidity in healthy volunteers: comparison with ranitidine and placebo.

In a series of double-blind randomized studies in normal volunteers using continuous intragastric pH monitoring, the effects of different dosage regimens of roxatidine, a new H2-receptor antagonist, were compared with placebo and ranitidine. Roxatidine acetate, 75 mg twice daily, decreased median 24 h gastric acidity from pH 1.6 to 3.2 and median nocturnal acidity from 1.5 to 3.0. Roxatidine acetate, 150 mg at bedtime, raised median 24 pH of the same 17 subjects to 2.4 and nocturnal pH to 5.9. In another series of experiments, 150 mg roxatidine acetate at bedtime was as effective as ranitidine 300 mg nocte raising median nocturnal pH (14 volunteers) from 1.4 to 6.65 compared to 6.7, respectively. However, when drugs were taken after the evening meal (post cenam nocte, pcn) roxatidine acetate 150 mg was less potent than ranitidine 300 mg with median night-time pH rising from 1.3 to 3.2 and 4.0, respectively, in 28 volunteers. Roxatidine acetate 300 mg pcn raised the pH to 4.9 suggesting that roxatidine is 1-2 times as potent as ranitidine, on a milligram-for-milligram basis.

The effects of roxatidine acetate on 24-hour intragastric acidity. Investigations in healthy volunteers and comparison with ranitidine and placebo.

In a series of double-blind randomised studies in normal volunteers with continuous intragastric pH monitoring, the effects of different dosage regimens of roxatidine acetate, a new H2-receptor antagonist, were compared with placebo and ranitidine. Roxatidine acetate 75 mg twice daily decreased median 24-hour gastric acidity from pH 1.6 to 3.2 and median nocturnal acidity from 1.5 to 3.0. Roxatidine acetate 150 mg at bedtime raised median 24-hour pH in the same 17 subjects to 2.4 and nocturnal pH to 5.9. In the second experiment, in 14 volunteers, roxatidine acetate 150 mg at bedtime was as effective as ranitidine 300 mg at night, raising median nocturnal pH from 1.4 to 6.65 compared to 6.7 for ranitidine. However, when drugs were taken after the evening meal (post cenam nocte; PCN) roxatidine acetate 150 mg was less potent than ranitidine 300 mg, with median night-time pH rising from 1.3 to 3.2 and 4.0, respectively, in 28 volunteers. Roxatidine acetate 300 mg PCN produced the greatest rise of pH, to 4.9, suggesting that the true potency ratio of the 2 drugs is between 1 and 2.

Assessment of intragastric acidity in man: modern aspects, reproducibility of intragastric pH-monitoring, and pharmacodynamic results obtained with H2-receptor antagonists.

Unlike other methods for assessing intragastric pH or total acid output, the reproducibility of ambulatory pH-monitoring is excellent but is critically dependent on the electrode system and the recording device. In three double-blind randomized studies in normal volunteers the effects of different dosage regimens of roxatidine acetate were compared with placebo and ranitidine. Roxatidine acetate, 75 mg twice daily, raised median 24-h gastric pH from 1.6 to 3.2 and median nocturnal pH from 1.5 to 3.0 Roxatidine acetate, 150 mg at bedtime, raised median 24-h pH to 2.4 and nocturnal pH to 5.9. Roxatidine acetate, 150 mg at bedtime, was as effective as ranitidine, 300 mg at night, in raising median nocturnal pH. However, when drugs were taken after the evening meal, 150 mg roxatidine acetate was less potent than 300 mg ranitidine or 300 mg roxatidine acetate.

Double blind comparison of the effects of cimetidine, ranitidine, famotidine, and placebo on intragastric acidity in 30 normal volunteers.

Continuous measurement of 24 hour intragastric acidity was carried out in 30 normal volunteers during treatment with placebo, cimetidine 800 mg, ranitidine 300 mg, and famotidine 40 mg in a double blind study. Medication was taken after the evening meal (post cenam nocte, PCN). Median 24 hour acidity decreased with all H2-receptor antagonists from 25.1 mmol/l on placebo to 10 mmol/l (-60.1%) during cimetidine, to 3.2 mmol/l (-87.25%) during ranitidine and to 2.5 mmol/l (-90.0%) during famotidine treatment (p less than 0.0005). All drugs significantly inhibited night time acidity but only famotidine decreased acidity during the late morning compared with placebo. Significantly greater acid reduction was seen with famotidine and ranitidine compared with cimetidine but no difference was found between famotidine and ranitidine.

Comparison of ranitidine 300 mg twice daily, 300 mg at night and placebo on 24-hour intragastric acidity of duodenal ulcer patients.

Continuous measurement of 24-hour intragastric acidity was performed in 12 duodenal ulcer patients in remission during treatment with placebo, ranitidine 300 mg nocte and ranitidine 300 mg b.d. Median 24-hour acidity was 79.4 mmol litre-1 during placebo treatment; it decreased to 28.2 mmol litre-1 during treatment with ranitidine 300 mg nocte and to 3.6 mmol litre-1 during treatment with ranitidine 300 mg b.d. The two regimens decreased intragastric acidity to a similar degree during the night, but significantly greater inhibition of daytime and 24-hour acidity followed use of ranitidine 300 mg b.d.

Single dose treatment with H2 receptor antagonists: is bedtime administration too late?

Using ambulatory ph-metry, intragastric acidity was measured over three separate 24 hour periods in each of 12 healthy volunteers receiving either (a) placebo (1800 h and 2200 h), (b) 300 mg ranitidine (1800 h) and placebo (2200 h), or (c) placebo (1800 h) and 300 mg ranitidine (2200 h). Ranitidine was significantly more effective in decreasing 24 h median intragastric acidity when the drug was administered at 1800 h rather than at 2200 h. Median pH (and interquartile range) was 1.45 (1.4-1.7) on placebo, 2.55 (2.05-3.2) on ranitidine given at 2200 h and 3.35 (2.5-3.85) on ranitidine given at 1800 h (p less than 0.004). The total duration of highly acidic electrode readings (pH less than 1.5) over a 24 h period was reduced significantly by administering the H2-receptor antagonist at 1800 h compared with the later administration. It is suggested that treatment of duodenal ulcers by single administration of ranitidine in the early evening should be evaluated by clinical trial.