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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.
K Matsuda, and
K Ohnishi, and
E Misaka, and
M Yamazaki
April 1984,
Clinical science (London, England : 1979),
K Matsuda, and
K Ohnishi, and
E Misaka, and
M Yamazaki
February 1990,
Clinical science (London, England : 1979),
K Matsuda, and
K Ohnishi, and
E Misaka, and
M Yamazaki
March 1979,
Acta physiologica Scandinavica,
K Matsuda, and
K Ohnishi, and
E Misaka, and
M Yamazaki
February 1986,
Clinical nephrology,
K Matsuda, and
K Ohnishi, and
E Misaka, and
M Yamazaki
January 1988,
Nephron,
K Matsuda, and
K Ohnishi, and
E Misaka, and
M Yamazaki
July 1985,
Research communications in chemical pathology and pharmacology,
K Matsuda, and
K Ohnishi, and
E Misaka, and
M Yamazaki
August 1984,
Israel journal of medical sciences,
K Matsuda, and
K Ohnishi, and
E Misaka, and
M Yamazaki
June 1981,
Prostaglandins,
K Matsuda, and
K Ohnishi, and
E Misaka, and
M Yamazaki
October 1987,
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme,
K Matsuda, and
K Ohnishi, and
E Misaka, and
M Yamazaki
January 1982,
Hypertension (Dallas, Tex. : 1979),
