The effect of indomethacin-induced gastric mucosal injury on 24-h intragastric acidity and plasma gastrin concentration in healthy volunteers.
OBJECTIVE
To determine the influences of prostaglandin inhibition by indomethacin on 24-h intragastric acidity and plasma gastrin concentration, related to gastric mucosal injury.


METHODS
A pre- and post-treatment study design was employed in 10 Helicobacter pylori negative healthy male subjects. All subjects underwent upper gastrointestinal endoscopy at least 3 days before and after 7 days dosing with indomethacin 50 mg t.d.s. Mucosal damage was scored according to the Lanza method, and biopsies were taken for H. pylori status and assay of mucosal concentrations of prostaglandin (PG)E2 and leukotriene (LT)B4. Before and on the last day of dosing, intragastric acidity was measured by continuous 24-h pH monitoring, and plasma gastrin levels determined by radioimmunoassay in blood samples collected over the same period.


RESULTS
All subjects completed the study and no serious adverse events were reported. The mucosal injury score increased significantly from 0 (0-2) to 3.4 (0-8) (mean and range of values, P < 0.05) after dosing with indomethacin. No differences were observed in 24-h mean pH or meal stimulated plasma gastrin concentrations. Mucosal PGE2 and LTB4 were unchanged 8-10 h after the last indomethacin dose.


CONCLUSIONS
Endogenous prostaglandins do not appear to alter intragastric acidity or gastrin secretion, in contrast to the PGE analogues, whose effects must be more pharmacological than physiological.
Rademaker
J W
JW
Division of Gastroenterology, McMaster University Faculty of Health Sciences, Hamilton, Ontario, Canada.
Rainsford
K D
KD
Stetsko
P I
PI
Johnson
D M
DM
Chiba
N
N
McDonald
T M
TM
Hunt
R H
RH
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D015232:Dinoprostone / Q000032:analysis; D004386:Duodenum / Q000187:drug effects; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005755:Gastrins / Q000097:blood*; D005773:Gastroscopy; D006801:Humans; D007213:Indomethacin / Q000009:adverse effects*; D007975:Leukotriene B4 / Q000032:analysis; D008297:Male; D013270:Stomach / Q000187:drug effects* / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005755:Gastrins; D007975:Leukotriene B4; D015232:Dinoprostone; D007213:Indomethacin