Extraction and metabolism of lidocaine in rat liver

The use of lidocaine as an oral antiarrhythmic drug is limited by its rapid disposition in the liver. In accordance with this we found that the drug was completely extracted during one passage through the perfused rat liver. The drug binds to rat liver microsomes with a type I spectral change of unusually high affinity. It is rapidly de-ethylated by the microsomes with an apparent Vmax of about 15 nmol per mg protein x min. The apparent Km for this reaction is about 250 muM. The reaction occures at about the same rate in isolated rat liver cells. We believe that the high affinity of lidocaine for the cytochrome P-450 system, as indicated by its type I spectral change, as well as the rapid oxidation of the drug are the two main determinants for the marked liver extraction and first pass effect of the drug.