The coadministration of paroxetine and low-dose aspirin synergistically enhances gastric ulcerogenic risk in rats.
Paroxetine is often coadministered with low-dose aspirin to treat cerebral infarction patients with depression. In order to assess the ulcerogenic risk induced by the coadministration of these drugs, we examined their effects on gastric secretion using the pylorus ligation method and determined the prostaglandin E(2) (PGE(2)) content in the gastric mucosa using enzyme immunoassay (EIA). Paroxetine stimulated the gastric fluid secretion and acid output, dose-dependently, however, it had no effect on the PGE(2) content in the gastric mucosa. Furthermore, exogenous serotonin inhibited both the gastric fluid secretion and the acid output. The coadministration of low-dose aspirin and paroxetine significantly enhanced the gastric fluid secretion and acid output, thus resulting in gastric bleeding, but it hardly affected the PGE(2) content in the gastric mucosa. The stimulation of gastric secretion by the coadministration of low-dose aspirin and paroxetine is therefore considered to play an important role in the development of gastric injuries.
Yamaguchi
Takumi
T
Division of Pharmacy, Ehime University Hospital, Toon, Japan.
Hidaka
Noriaki
N
Suemaru
Katsuya
K
Araki
Hiroaki
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D001241:Aspirin / Q000008:administration & dosage / Q000633:toxicity*; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000473:pathology; D008297:Male; D017374:Paroxetine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000633:toxicity*; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin; D015232:Dinoprostone; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors