Effects of tobacco smoke exposure on the kinetics of bupivacaine in mice

The aim of this work was to determine the effects of different time of tobacco smoke exposure on pharmacokinetics of bupivacaine in mice. Mice were exposed to tobacco smoke during 4 days (group T4) or 8 days (group T8) using the Hamburg II smoking machine. Controls were exposed under the same experimental conditions but without tobacco smoke. Serum pharmacokinetic parameters, protein or erythrocyte binding of bupivacaine were measured on the 4th and 8th day of exposure. Furthermore the urines were kept during 24 hours and urine metabolite percentages were determined. After the short exposure (4 days), no differences between treated and control groups were reported in contrary to the longer exposure (8 days), where data showed a significantly increased metabolism and elimination of bupivacaine in the treated group compared to the controls. Our data indicate that tobacco smoke acts at different levels i.e. metabolism, elimination and binding of bupivacaine. Tobacco smoke exposure increases the metabolism of bupivacaine by activating the hydroxylation route and by inducing an important elimination of 3OH-bupivacaine. Besides, it increases the permeability of the cell membranes and facilitates the penetration of bupivacaine and desbutylbupivacaine in erythrocytes.