A discordance of the cytochrome P450 2C19 genotype and phenotype patients with advanced cancer

Marion L. Williams, Pankaj Bhargava, Ilham Cherrouk, John L. Marshall, David A. Flockhart, Irving W. Wainer

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Aims. To examine the relationship between cytochrome P450 2C19 (CYP2C19) genotype and expressed metabolic activity in 16 patients with advanced metastatic cancer. Methods. Individual CYP2C19 genotypes were determined by PCR-based amplification, followed by restriction fragment length analysis, and compared with observed CYP2C19 metabolic activity, as determined using the log hydroxylation index of omeprazole. Results. All 16 patients had an extensive metabolizer genotype. However, based on the antimode in a distribution of log omeprazole hydroxylation indices from healthy volunteers, four of the patients had a poor metabolizer phenotype and there was a general shift of the remaining 12 patients towards a slower metabolic phenotype. This suggests a reduction in metabolic activity for all patients relative to healthy volunteers. A careful analysis of patient medical records failed to reveal any drug interactions or other source for the observed discordance between genotype and phenotype. Conclusions. There are no previous reports of a 'discordance' between genotype and expressed enzyme activity in cancer patients. Such a decrease in enzyme activity could have an impact on the efficacy and toxicity of chemotherapeutic agents and other drugs, used in standard oncology practice.

Original languageEnglish (US)
Pages (from-to)485-488
Number of pages4
JournalBritish Journal of Clinical Pharmacology
Volume49
Issue number5
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Cytochrome P-450 Enzyme System
Genotype
Phenotype
Neoplasms
Omeprazole
Hydroxylation
Healthy Volunteers
Enzymes
Drug Interactions
Medical Records
Polymerase Chain Reaction
Pharmaceutical Preparations

Keywords

  • Advanced cancer patients
  • CYP2C19
  • Genotype
  • Phenotype

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Williams, M. L., Bhargava, P., Cherrouk, I., Marshall, J. L., Flockhart, D. A., & Wainer, I. W. (2000). A discordance of the cytochrome P450 2C19 genotype and phenotype patients with advanced cancer. British Journal of Clinical Pharmacology, 49(5), 485-488. https://doi.org/10.1046/j.1365-2125.2000.00189.x

A discordance of the cytochrome P450 2C19 genotype and phenotype patients with advanced cancer. / Williams, Marion L.; Bhargava, Pankaj; Cherrouk, Ilham; Marshall, John L.; Flockhart, David A.; Wainer, Irving W.

In: British Journal of Clinical Pharmacology, Vol. 49, No. 5, 2000, p. 485-488.

Research output: Contribution to journalArticle

Williams, ML, Bhargava, P, Cherrouk, I, Marshall, JL, Flockhart, DA & Wainer, IW 2000, 'A discordance of the cytochrome P450 2C19 genotype and phenotype patients with advanced cancer', British Journal of Clinical Pharmacology, vol. 49, no. 5, pp. 485-488. https://doi.org/10.1046/j.1365-2125.2000.00189.x
Williams, Marion L. ; Bhargava, Pankaj ; Cherrouk, Ilham ; Marshall, John L. ; Flockhart, David A. ; Wainer, Irving W. / A discordance of the cytochrome P450 2C19 genotype and phenotype patients with advanced cancer. In: British Journal of Clinical Pharmacology. 2000 ; Vol. 49, No. 5. pp. 485-488.
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