Application to drug-food interactions of living cells as in vitro model expressing cytochrome P450 activity: enzyme inhibition by lemon juice

Classical inhibitors of human cytochrome P450 3A4 activity, such as ketocon azol and quercetin, are tested to prove the efficiency of a new metabolisat ion model using living entire cells. Grapefruit juice is a well-known poten t inhibitor of cytochrome P450 3A4 activity. With regard to the clinical re levance of grapefruit juice-drug interactions, an investigation of other co mmon juices is undertaken with this in vitro model. The CYP3A4 activity is measured by the formation of the 6 beta -hydroxytestosterone, which is quan tified by an isocratic high performance liquid chromatography. It is demons trated for the first time that lemon juice significantly inhibits by 60 +/- 3% the CYP3A4-mediated oxidation. Grapefruit juice inhibits this activity by 82 +/- 4%. The mechanism of lemon juice inhibition is competitive, where as it is mixed for grapefruit juice. These results suggest that our in vitr o model combined with our analytical method is applicable for the investiga tion of the inhibition of CYP3A4 not only by chemical inhibitors but also b y natural food products. (C) 2001 Elsevier Science B.V. All rights reserved .