Drug interactions and the cytochrome P450 system. The role of cytochrome P450 2C19

Abstract

On the basis of the data currently available, the wild type cytochrome P450 2C19 (CYP2C19) gene appears to be absent in 2 to 6% of Caucasian populations and up to 20% of Asian populations. A poor metaboliser phenotype therefore results. The CYP2C19 phenotype can be determined clinically by use of either mephenytoin or omeprazole as the probe. Since both drugs are metabolised primarily by CYP2C19 in human liver microsomes, they are both useful, competitive inhibitors of CYP2C19 activity available to researchers working in vitro. The 2 known mutant alleles of CYP2C19 do not result in the expression of active enzyme and can be tested by using small samples of whole blood. No rapid mutants have been identified. A number of drugs have been shown to inhibit CYP2C19 in vivo, including fluvoxamine and fluoxetine. Important drug interactions may result from inhibition of hepatic CYP2C19 activity in extensive metabolisers or from the interaction of CYP2C19 substrates with other pathways in poor metabolisers.