Pharmacokinetic and gastric secretory studies of ranitidine in man

Abstract

A sensitive and specific high pressure liquid chromatographic procedure for ranitidine estimation is described and pharmacokinetic studies in six healthy volunteers reported. Each subjects received 20 mg of ranitidine i.v.; 20 mg, 40 mg and 100 mg orally having fasted overnight and 100 mg with a standard meal. Following the i.v. dose, ranitidine plasma concentrations fell biexponentially with a distribution half-life of 6.1 +/- 0.9 min and a terminal elimination half-life of 1.9 +/- 0.1 h. The volume of distribution was 115 +/- 7 1 and the systemic plasma clearance 709 +/- 62 ml/min. After 20 mg oral doses the systemic availability was high (88 +/- 10%). Bioavailability was unaffected by food and AUC increased linearly with dose to 100 mg. Renal excretion of unchanged ranitidine was between 50 and 70% and a further 1-3% was excreted as desmethylranitidine. In separate studies, the inhibitory action of cimetidine and ranitidine on pentagastrin stimulated gastric acid output was compared in seven duodenal ulcer patients. Results so far indicate that ranitidine 150 mg i.v. produces a more pronounced and more prolonged suppression of pentagastrin stimulated gastric acid output than cimetidine 200 mg i.v. (p less than 0.001). Ranitidine produced a sustained near total (greater than 90%) suppression in acid output in the period 60 to 120 min after drug administration, whereas acid output with cimetidine was less and fell from 82 to 54% in the same period.