[Sensitivity of gastric parietal cells to histamine after administration of enprostil and ranitidine during 4 weeks in healthy subjects].
Parietal cell sensitivity is increased in patients with active duodenal ulcer. It has been shown to increase in healthy volunteers after a 4-week treatment with H2-receptor blockers. Metaanalyses of therapeutic trials have indicated that time to first relapse was longer after ulcer healing with prostaglandins (PG) than after healing with H2-receptor blockers, which might be due to a different effect of the two treatments on parietal cell sensitivity. OBJECTIVES--To study, in healthy volunteers, basal gastric acid secretion, acid secretory responses and parietal cell sensitivity to histamine before and after a 4-week treatment with enprostil (E) and ranitidine (R). METHODS--This was a randomized double-blind double-dummy crossover study. Twelve male healthy volunteers (22-44 years) were randomly assigned to receive a 4-week treatment with either E (35 micrograms bid) or R (150 mg bid). After a 2-month washout period, they were crossed to the alternate treatment. Basal acid output (BAO), acid secretory responses to low-dose histamine infusion (histamine dihydrochloride 2.5 micrograms/kg/h) (LDAO), to a high-dose histamine infusion (25 micrograms/kg/h) (HDAO) and parietal cell sensitivity (PCS = LDAO/HDAO x 100) were measured 24 hours before the first administration and 72 hours after the last administration of each medication. RESULTS--All secretory parameters were similar before treatment with E and R. As compared to pretreatment values: a) HDAO tended to increase after both treatments (NS); b) LDAO (m +/- sem) slightly increased after R (18.4 +/- 2.6 vs 13.9 +/- 3.3 mEq) (NS) but not after E (12.5 +/- 1.8 vs 13.2 +/- 1.9 mEq); c) PCS (m +/- sem) was unchanged after R (36 +/- 4 vs 33 +/- 6) but decreased after R (30 +/- 6 vs 36 +/- 0.5; P < 0.02). When secretory parameters after treatment with R and treatment with E were compared, the difference was significant for LDAO (P < 0.02) and PCS (P < 0.05). CONCLUSIONS--If also found in patients with duodenal ulcer disease, these results might, at least partly, explain the lesser propensity of the ulcers to relapse early after healing with PG than after healing with H2-receptor blockers. However enprostil has been with-drawn from the market and it is now well established that one factor influencing the relapse rate is the efficiency of the treatment given to achieve ulcer healing in eradicating Helicobacter pylori. Consequently, the interest of our results is presently mostly physiological.
Soulé
J C
JC
Service d'Hépato-Gastroentérologie, Hôpital Louis-Mourier, Colombes.
Larvol
L
L
Dutreuil
C
C
Ory-Lavollée
L
L
D000328:Adult; D004311:Double-Blind Method; D016620:Enprostil / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000378:metabolism*; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010295:Parietal Cells, Gastric / Q000187:drug effects*; D010919:Placebos; D011899:Ranitidine / Q000494:pharmacology*; D012016:Reference Values
D010919:Placebos; D006632:Histamine; D011899:Ranitidine; D016620:Enprostil
Sensibilité des cellules pariétales gastriques à l'histamine après administration pendant 4 semaines d'enprostil et de ranitidine chez le sujet sain.