Prolonged inhibition of meal-stimulated acid secretion and gastrin release following single subcutaneous administration of octreotide (SMS 201–995) in man

Single subcutaneous doses of the somatostatin analogue, SMS 201-995, were evaluated for the degree and duration of effects on acid secretion, serum gastrin levels, and gastric emptying in eight human male subjects (mean age 44 years) over an 8-h period. All the subjects received subcutaneous 50-micrograms and 100-micrograms doses of SMS 201-995 and placebo on three separate days in a double-blind random order. Drug or placebo was administered at time 0 followed by peptone meals at time 0, 2, 4, and 6-h. Peptone meals were evacuated at time 1, 3, 5 and 7-h to create 'basal' conditions between alternate hours. Gastric acid secretion was determined hourly beginning at time--1. Both the 50-micrograms and 100-micrograms doses of SMS 201-995 significantly inhibited 'basal' and peptone meal-stimulated gastric acid secretion throughout the 8-h measurement period. The minimum effective plasma concentration of SMS 201-995 for inhibition of peptone meal-stimulated gastric acid secretion was approximately 1000 pg/ml. Peptone meal-stimulated plasma gastrin concentrations were inhibited for 5 and 7 h after 50-micrograms and 100-micrograms doses of SMS 201-995, respectively, whereas 'basal' plasma gastrins were inhibited for 4 and 6 h, respectively. Gastric emptying determined by marker dilution was not significantly enhanced compared to placebo. These results indicate prolonged and potent effects of single subcutaneous doses of SMS 201-995 on peptone-meal stimulated acid secretion and gastrin release.