Effects of chronic NSAIDs on gastric mucosal injury related to mucosal prostanoids, and plasma drug concentrations in human volunteers.
The relationship between endoscopically observed gastric mucosal damage, elicited following repeated oral intake for 7 d of four NSAIDs, to their effects on antral and fundic production of PGE2, 6-keto-PGF1 alpha and TxB2 (assayed by GC-MS), mucosal histology and plasma concentration profiles was studied in 40 normal males. Subjects received azapropazone (APZ) 600 mg b.i.d., indomethacin (IND) 50 mg t.i.d., naproxen (NAP) 500 mg b.i.d., piroxicam (PIR) 20 mg qq.d., or one placebo capsule t.i.d. (N = 8/group). Plasma NSAIDs (HPLC) levelled at 7 d. Mucosal damage occurred in the antrum region with IND and NAP. APZ and PIR exhibited no differences compared to placebo. NAP and IND reduced all three prostanoids in the antrum while APZ and PIR were ineffective. Fundic PGE2 was reduced by IND, NAP and PIR; APZ had no effects. Thus, mucosal damage relates to effects on prostanoid production in the antrum but not in the fundus.
Rainsford
K D
KD
Department of Biomedical Sciences, McMaster University Faculty of Health Sciences, Hamilton, Ontario, Canada.
James
C
C
Johnson
D M
DM
Stetsko
P I
PI
Hill
R E
RE
Salena
B J
BJ
Hunt
R H
RH
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism*; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology; D001032:Apazone / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D005748:Gastric Fundus / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D008297:Male; D009288:Naproxen / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D010894:Piroxicam / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D011706:Pyloric Antrum / Q000187:drug effects / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010894:Piroxicam; D013929:Thromboxane B2; D009288:Naproxen; D015121:6-Ketoprostaglandin F1 alpha; D001032:Apazone; D015232:Dinoprostone; D007213:Indomethacin