In order to investigate whether liver slices are a valuable tool for the assessment of drug metabolism in human liver, we compared the phase I metabolism of lidocaine in human liver slices and hepatocytes prepared from three human livers. Lidocaine is mainly metabolised to monoethylglycinexykdide (MEGX) via a cytochrome P450-mediated N-deethylation. The results indicate that the three livers showed considerable inter-individual differences in the rate of formation of MEGX, and that this difference was equally reflected in slices and isolated cells. The use of liver slices is still under development, and optimal incubation conditions still need to be assessed. However, these results suggest that, in slices of 200–300μm thickness, virtually all hepatocytes are involved in the biotransformation of lidocaine, and that the metabolic activity is preserved equally well as in isolated hepatocytes.
Expression of cytochrome P450 isozyme transcripts and activities in human livers