Depression of drug metabolism in the mouse by a combination of Mycobacterium butyricum and anaesthetics.

1 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. 2 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. 3 Indomethacin inhibited hind paw oedema in the mouse but did not affect ketamine-Mycobacterium butyricum-induced depression of drug metabolism. 4 Prolongation of ketamine-induced anaesthesia by combination with Mycobacterium butyricum at day 5 correlated with the degree of hind paw inflammation at this time. 5 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.