Decrease of urinary prostaglandin E2 and prostaglandin F2 alpha excretion by nonsteroidal anti-inflammatory drugs in rats. Relationship to anti-inflammatory activity.
An analytical method for measuring in vivo inhibition of prostaglandin (PG) synthesis by nonsteroidal anti-inflammatory drugs was developed for estimation of urinary prostaglandin levels in rats. Drugs were administered orally to rats (Wistar, male, 200-250 g), and water (2.5 ml/100 g body weight) was given 1 hr after drug administration to yield a constant volume of urine. Urine was collected for 4 hr after drug administration, and urinary PGE2 and PGF2 alpha were determined by radioimmunoassay. The urine volume in the 4-hr period was 5.0 +/- 0.30 ml per rat, and prostaglandin contents in the 4-hr urine were 4.56 +/- 0.56 ng PGE2 and 1.31 +/- 0.24 ng PGF2 alpha per rat in the no-drug control group. Administration of nonsteroidal anti-inflammatory drugs decreased the urinary PGE2 and PGF2 alpha dose dependently. The activities of ten typical nonsteroidal anti-inflammatory drugs in reducing urinary PGE2 excretion were compared with their anti-inflammatory activities in rats. A close correlation (r = 0.98, P less than 0.001) between the dose required for 50% reduction of urinary PGE2 excretion and the dose required for 50% inhibition of carrageenin edema was found for each drug. These drugs were also tested for their inhibitory effects on PGE2 biosynthesis in a cultured system of mouse 3T6 fibroblast cells and on prostaglandin synthesizing system in bovine seminal vesicle microsomes. No close correlation was observed between anti-inflammatory activities and inhibition of prostaglandin biosynthesis in vitro.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002417:Cattle; D015237:Dinoprost; D015232:Dinoprostone; D004487:Edema / Q000188:drug therapy; D005347:Fibroblasts / Q000378:metabolism; D008297:Male; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D011458:Prostaglandins E / Q000652:urine*; D011460:Prostaglandins F / Q000652:urine*; D051381:Rats; D011919:Rats, Inbred Strains; D012669:Seminal Vesicles / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D011458:Prostaglandins E; D011460:Prostaglandins F; D015237:Dinoprost; D015232:Dinoprostone