Effect on gastric and duodenal mucosal prostaglandins of repeated intake of therapeutic doses of naproxen and etodolac in rheumatoid arthritis.
The synthesis of gastric and duodenal mucosal prostaglandin E2, prostaglandin I2, and thromboxane B2 during a 60 minute incubation of biopsy specimens, the degree of endoscopic and histological damage, and the anti-inflammatory response were all studied after a four week, double blind study of therapeutic doses of two non-steroidal anti-inflammatory drugs, naproxen and etodolac, received by 27 patients with active rheumatoid arthritis (13 receiving naproxen, 14 etodolac). Prostaglandin values after treatment did not differ from the baseline levels when all the patients were analysed as one group. Subgroup analysis showed that naproxen suppressed gastric prostaglandin E2 from a median of 29 to 9 ng/mg protein, duodenal prostaglandin E2 from 34 to 11 ng/mg, and duodenal prostaglandin I2 from 62 to 15 ng/mg protein. No overall suppression occurred with etodolac. Also, on the second assessment patients receiving naproxen had lower gastric and duodenal prostaglandin E2 and prostaglandin I2, but higher values of duodenal thromboxane B2, than patients receiving etodolac. Both drugs had comparable anti-arthritic activity and caused microscopic gastritis in similar proportions of patients. No correlation was detected between prostaglandin values and the mucosal damage which developed in seven patients receiving naproxen (54%) and three receiving etodolac (21%). These findings indicate that, unlike naproxen, etodolac does not seem to affect gastric or duodenal prostaglandin synthesis; other mechanisms of injury need to be considered.
Taha
A S
AS
Gastroenterology Unit, Glasgow Royal Infirmary, Scotland.
McLaughlin
S
S
Holland
P J
PJ
Kelly
R W
RW
Sturrock
R D
RD
Russell
R I
RI
D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D015232:Dinoprostone / Q000096:biosynthesis; D004311:Double-Blind Method; D004386:Duodenum / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis; D017308:Etodolac; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007210:Indoleacetic Acids / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000627:therapeutic use*; D011446:Prospective Studies; D011453:Prostaglandins / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007210:Indoleacetic Acids; D011453:Prostaglandins; D017308:Etodolac; D013929:Thromboxane B2; D009288:Naproxen; D011464:Epoprostenol; D015232:Dinoprostone