The kinetics of inhibition of hepatic drug metabolism by prostaglandins in rabbits.

The in vitro effects of prostaglandin A1 and prostaglandin E1 on the hepatic microsomal metabolism of type I (aminopyrine) and type II (p-chloro-N-methylaniline and aniline) drug substrates in rabbits were investigated. Both prostaglandins competitively inhibited aminopyrine N-demethylation to the same extent with a 500 microM prostaglandin concentration decreasing metabolism by approximately 50 percent. Prostaglandin A1 and prostaglandin F1 decreased p-chloro-N-methylaniline biotransformation, and prostaglandin E1 depressed aniline metabolims, via mixed-inhibition kinetics. The degree of inhibition was greatest with aniline as substrate. Aniline (0.125 mM) metabolism was inhibitied 49 percent and 71 percent by 100 microM and 500 microM prostaglandin E1, respectively.