Decrease of urinary prostaglandin E 2 and prostaglandin F 2α excretion by nonsteroidal anti-inflammatory drugs in rats : Relationship to anti-inflammatory activity

Abstract

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 PGE 2 and PGF 2awere 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 PGE 2 and 1.31 ± 0.24 ng PGF 2α per rat in the no-drug control group. Administration of nonsteroidal anti-inflammatory drugs decreased the urinary PGE 2 and PGF 2a dose dependently. The activities of ten typical nonsteroidal anti-inflammatory drugs in reducing urinary PGE 2 excretion were compared with their anti-inflammatory activities in rats. A close correlation ( r = 0.98, P < 0.001) between the dose required for 50% reduction of urinary PGE 2 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 PGE 2 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. addressed.