CYP2D6 MESSENGER-RNA EXPRESSION IN CIRCULATING PERIPHERAL-BLOOD MONONUCLEAR-CELLS CORRELATES WITH IN-VIVO DEBRISOQUINE HYDROXYLASE-ACTIVITYIN EXTENSIVE METABOLIZERS

Extensive metabolizers of drugs which are oxidized by cytochrome P450s show wide interindividual variability in drug metabolism. Elucidation of the relationship between specific P450 isozyme mRNA expression and variability in metabolism of specific drugs could improve understandi ng of the molecular mechanism involved. In this study, a novel non-rad iometric reverse transcription polymerase chain reaction based assay w as used to quantify CYP2D6 mRNA levels in peripheral blood mononuclear cells in twelve human volunteers who were phenotyped as extensive met abolizers of debrisoquine. We report a significant correlation (r=.724 , p=.008) between CYP2D6 mRNA levels in circulating peripheral blood m ononuclear cells and the in vivo debrisoquine recovery ratio. This sug gests that interindividual variability in extensive metabolizers could be related, in part, to differences in gene expression. Circulating p eripheral blood mononuclear cells can provide an accessible ex vivo me asure of this phenomenon.