A discordance between individual genotypes for cytochrome P450 2C19 (CYP2C19) and expressed CYP2C19 phenotypes has been observed in 16 Caucasian patients with advanced cancer. CYP2C19 genotypes were determined by PCR-based amplification followed by restriction fragment length analysis. CYP2C19 phenotypes were determined using log omeprazole hydroxylation index. All 16 patients were found to have an EM genotype, which was expected since only 3% of Caucasians possess a PM geno-type for CYP2C19. However, 4 of the patients (25%) were found to have PM phenotypes. The remaining 12 patients also displayed a statistically significant shift towards the PM phenotype, relative to results from healthy volunteers (P=0.002, Wilcoxon Signed-Rank test). None of the 16 patients were receiving any known CYP2C19 inhibitors at the time of phenotyping and there were no likely drug interactions. The 4 patients whose genotype and phenotype were discordant were all suffering from metastasized adenocarcinomas. No two patients had received the same anticancer therapy and therefore, no one drug could be identified as the source of the observed EM to PM transition. In conclusion, such changes in CYP2C19 activity could have a considerable impact on the clinical efficacy and toxicity of therapeutic agents.
ASJC Scopus subject areas
- Pharmacology (medical)