1986 Volume 46 Issue 3 Pages 315-321
Effects of alminoprofen, (±) -2- [p- [ (2-methylallyl) amino] phenyl] propionic acid, a new analgesic anti-inflammatory drug, on drug-metabolizing enzymes and fine-structure in rat liver were investigated compared with ibuprofen, ketoprofen and flurbiprofen. Aminopyrine N-demethylase and aniline hydroxylase activities and cytochrome P-450 contens were decreased from 6hr to 48hr after a single administration of alminoprofen (35mg/kg and 50mg/kg p. o.) . In fine-structure of liver, alminoprofen caused the morphological changes such as disarrangement and enlargement of rough endoplasmic reticulum (rER), detachment of ribosome from the rER and increase in smooth endoplasmic reticulum (sER) . Nevertheless, the decreases in drug-metabolizing enzyme activities and morphological changes induced by alminoprofen were reversible. The drug-metabolizing enzyme activities were increased transiently by administration of ibuprofen, ketoprofen and flurbiprofen. Morphological changes for endoplasmic reticulum (ER) prolonged until 96hr after administration of ibuprofen (50mg/kg p.o.) . From these results, the inhibition of hepatic drug-metabolizing enzyme activity by alminoprofen was thought a reversible response with the morphological changes in the liver. It is suggested that these changes on drug-metabolizing enzyme activity and fine-structure of liver was an adaptive reaction of liver induced by after a single administration of alminoprofen.
