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Effect of ring substitution on the metabolic fate and anti-inflammatory activity of some prodolic acid analogs

WT Robinson, RR Martel, E Ferdinandi and M Kraml

Prodolic acid, 1-n-propyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1- acetic acid, exhibits potent anti-inflammatory activity in adjuvant arthritic rats. The potency of prodolic acid is enhanced by indole ring substitution. This increase correlated well with higher and sustained drug concentrations in the serum of normal animals. Pharmacokinetic studies demonstrated that ring substitution prolonged the serum half- life without affecting the absorption or volume of distribution. Because, in the rat, indole ring hydroxylation is a major pathway for the disposition of prodolic acid, we ascribe the increased pharmacological activity of ring substituted derivatives to the interference of substituents with the hydroxylation reaction.

Volume 203, Issue 3, pp. 729-735, 12/01/1977
Copyright © 1977 by American Society for Pharmacology and Experimental Therapeutics






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Copyright © 1977 by the American Society for Pharmacology and Experimental Therapeutics.