Pharmacodynamics of intravenous ranitidine after bolus and continuous infusion in patients with healed duodenal ulcers

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Abstract
Fifteen adult men who had histories of duodenal ulcer disease were studied for 24 hours during treatment with varying intravenous doses of ranitidine (50 mg every 8 hours, 100 mg every 12 hours, 6.25 mg/hr continuous infusion, and 10 mg/hr continuous infusion) and placebo. Gastric pH was monitored under fasting conditions by means of an indwelling pH sensitive electrode. The continuous infusion regimes provided the most constant level of acid suppression. A "breakthrough" decrease in gastric pH began at approximately 6 PM at the 6.25 mg/hr dose level. The drop in pH at the 10 mg/hr dose level was less impressive. Ranitidine, 100 mg every 12 hours, resulted in better acid suppression than the regimen of 50 mg every 8 hours. A gastric pH .gtoreq. 4 was achieved 35 to 50 minutes after the start of administration for all regimens. The median effective concentration (EC50) of ranitidine was approximately 45 ng/ml. Continuous infusion regimens, with a dosage adjustment for the time of day, may be the optimal dosage regimen for patients requiring continuous protection from gastric damage by hydrochloric acid. Bolus loading doses are not required to speed the onset of the effect in the clinical setting.