Abstract
Effect of repeated oral administration of alminoprofen, a new analgesic anti-inflammatory drug, on drug-metabolizing enzyme activity and fine-structure in rat liver were investigated compared with ibuprofen, flurbiprofen and ketoprofen. The drug-metabolizing enzyme activity was not affected by alminoprofen at doses of 20, 35 and 50mg/kg daily for 3days. Aminopyrine N-demethylase and aniline hydroxylase activities were inhibited by the administration of alminoprofen for 7days or 14days. Furthermore, when administered for 14days at dose of 50mg/kg, alminoprofen caused the decrease of cytochrome P-450 contents, too. After washing out for lOdays, these changes returned to the control level. On repeated oral administration of alminoprofen (35 and 50mg/kg) for 3 days or 7 days to rats, the morphological changes of fine-structure showed the decrease and enlargement of rough endoplasmic reticulum (rER), the detachment of ribosome from rER and the increase in smooth endoplasmic reticulum (sER) . On the other hand, trimethadione metabolic rate was not reduced by the repeated oral administration of alminoprofen for 14 days. From these results, the repeated oral administration of alminoprofen showed the reversible inhibition of drug-metabolizing enzyme activity and a transitory response with the morphological changes for ER in rat liver. These morphological changes for ER did not correlated with the drug-metabolizing enzyme activity. It was suggested that the changes caused by almino profen were physiological adaptive response, and alminoprofen did not induced a hindrance to hepatic functions.
