DEPRESSION OF DRUG-METABOLISM IN THE MOUSE BY A COMBINATION OF MYCOBACTERIUM-BUTYRICUM AND ANESTHETICS

Subcutaneous injection of Mycobacterium butyricum suspended in mineral oil into the mouse hind paw caused an oedematous local inflammation. Hind paw swelling was maximum 5 days after injection and was still apparent at day 30. Drug metabolism in vivo (as monitored by ketamine‐ or pentobarbitone‐induced sleeping times) was not affected by the inflammatory disease. However, administration of ketamine or pentobarbitone at day 1 led to significantly elevated sleeping times when the mice showing local inflammation were retested at day 5 with the anaesthetics. Indomethacin inhibited hind paw oedema in the mouse but did not affect ketzmine‐Mycobacter‐ium butyricum‐induced depression of drug metabolism. Prolongation of ketamine‐induced anaesthesia by combination with Mycobacterium butyricum at day 5 correlated with the degree of hind paw inflammation at this time. The data suggest that anaesthetics (i.e., ketamine and pentobarbitone) may sensitize hepatic membranes to the effect of Mycobacterium butyricum or some toxic compound elaborated during the active phase of inflammation. 1979 British Pharmacological Society