Synergistic interaction between an H2-receptor antagonist and enprostil on 24-hour intragastric pH, serum gastrin concentration, and tissue immunoperoxidase staining for gastrin, somatostatin, and serotonin in a patient with metastatic gastrinoma.
A 56-year-old woman newly diagnosed as having Zollinger-Ellison syndrome due to a metastatic gastrinoma underwent 24-hour intragastric pH monitoring, serum gastrin (total, G-17 and G-34) measurements, and immunoperoxidase staining of duodenal, antral, and gastric body biopsies for gastrin, somatostatin, and serotonin. Determinations were made while the patient was given different doses of ranitidine, enprostil (a synthetic orally administered prostaglandin E2), or ranitidine plus enprostil. Following are the findings from this single-patient study: Intragastric pH was persistently low but varied in response to food when the patient was given ranitidine. Immunocytochemical staining of antral biopsies obtained before the patient was treated revealed a reduced number of cells containing G-17 and G-34 but an increase in the antral somatostatin-containing D-cells. Treatment with 35 micrograms of enprostil BID plus 300 mg of ranitidine BID for two and 11 weeks was associated with an increased number of duodenal G-cells, a decrease in antral D-cells, and a decrease in the number of antral serotonin-containing cells. Enprostil in a dosage of 35 or 70 micrograms BID had no effect on intragastric pH, but when enprostil was given in combination with ranitidine, postprandial and nocturnal intragastric alkalinity was accentuated along with a return of duodenal and antral G-cells and a loss of the antral D-cell hyperplasia. Optimal pH control was achieved with 300 mg of ranitidine BID; more frequent dosing with ranitidine did not further increase intragastric pH. Both the total serum gastrin concentration and G-17 levels fluctuated in response to meals. The serum concentrations of total gastrin, G-17, and G-34 were reduced with enprostil and with ranitidine.
D000971:Antineoplastic Combined Chemotherapy Protocols; D004357:Drug Synergism; D016620:Enprostil; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D011459:Prostaglandins E, Synthetic / Q000008:administration & dosage*; D011899:Ranitidine / Q000008:administration & dosage*; D012701:Serotonin / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism; D015043:Zollinger-Ellison Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary
D005755:Gastrins; D011459:Prostaglandins E, Synthetic; D012701:Serotonin; D013004:Somatostatin; D011899:Ranitidine; D016620:Enprostil