The effects on gastroduodenal mucosa of a new nonsteroidal anti-inflammatory drug, amtolmetin-guacyl, versus piroxicam in healthy volunteers: a short-term, double-blind, endoscopically controlled study.
OBJECTIVE
Amtolmetin-guacyl (AMG) (2-[2[1-methyl-5-(4-methylbenzoyl) pyrrol-2-yl] acetamido] acetic acid 2-methoxyphenyl ester) is a recent drug that, in preliminary studies, has shown effective anti-inflammatory properties with improved gastrointestinal safety. Our study was designed to investigate the effects of AMG and piroxicam on gastroduodenal mucosa in healthy volunteers.


METHODS
Forty-two healthy volunteers aged 18--45 years were randomized in a double-blind manner to AMG 1200 mg for 2 days and 600 mg for 12 days, or piroxicam 40 mg for 2 days and 20 mg for 12 days. Endoscopic evaluation and laboratory tests were performed at baseline and at the end of the treatment. The mucosa was evaluated by endoscopy using a predefined scale: the score could range from 0 to 4. Only volunteers with endoscopy grade 0-1 entered the trial.


RESULTS
The median post-treatment endoscopy gastric injury scores were 1 (range 0--4) in the AMG-treated volunteers and 3 (range 0--4) in the piroxicam-treated volunteers (P = 0.04). There were two cases with an endoscopic gastric score of 4 in the AMG group, and seven in the piroxicam group (P = 0.1). The corresponding values in the duodenum were 1/21 volunteers in the AMG group and 1/21 in the piroxicam group. Eight out of 11 subjects with an endoscopic score of 4 were Helicobacter pylori negative, and 3/11 were infected by the micro-organism. Different adverse reactions were reported by 15/21 volunteers (71%) in the AMG group and by 12/21 (57%) in the piroxicam group. None of these events resulted in interruption of the study.


CONCLUSIONS
AMG is a new anti-inflammatory drug with limited gastric toxicity. If these findings are confirmed on a wider scale in long-term trials, then the drug might become a valid alternative to current treatments, especially for patients such as those with rheumatoid arthritis who need steroids and second-line drugs simultaneously.
Lazzaroni
M
M
L Sacco University Hospital, Milan, Italy.
Anderloni
A
A
Bianchi Porro
G
G
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology*; D004311:Double-Blind Method; D004386:Duodenum / Q000187:drug effects* / Q000473:pathology; D004724:Endoscopy; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D005998:Glycine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D010894:Piroxicam / Q000009:adverse effects / Q000494:pharmacology*; D011758:Pyrroles / Q000009:adverse effects / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects* / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011758:Pyrroles; C065762:ST 679; D010894:Piroxicam; D005998:Glycine