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In‐vitro biotransformation of antipyrine, lignocaine and propranolol in the liver of rats with turpentine‐induced inflammation

In rats with inflammation induced by turpentine injection, changes in drug disposition occur in‐vivo and in the perfused isolated liver. Therefore the biotransformation of a low extraction drug, antipyrine, and of two high extraction drugs, lignocaine and propranolol, has been evaluated in the 9000g supernatant fraction of the liver of turpentine‐treated rats. Aminopyrine N‐demethylase activity and cytochrome P450 content were also measured. Turpentine treatment significantly reduced the in‐vitro breakdown of the three drugs; aminopyrine N‐demethylase activity and cytochrome P450 content were also decreased. Similar results were found in the proadifen‐treated rats, except that in those, the cytochrome P450 content was slightly increased. The changes in drug disposition seen after turpentine‐induced inflammation, could therefore be due in part to a change in hepatic enzymatic activity.