title: Genotype/phenotype comparisons: a probe for the effect of disease progression on drug metabolism.
abstract: The effect of disease state on drug metabolism has been investigated using the relationship between genotype and metabolic phenotype. The two polymorphic probes, N-acetyltransferases-2 (NAT2) and cytochrome P450 2C19 (CYP2C19), were respectively used in HIV+/AIDS patients and patients with advanced cancer. The results of the studies suggest that advanced disease produces discordances between genotype and phenotype, indicating a reduction in the metabolic capabilities of these individuals. Thus, polymorphic enzymes such as CYP2C19 and NAT2 can be used to probe changes in drug-metabolizing enzyme capacities. The development of genotype/phenotype discordances should reflect general changes in metabolic capabilities and, thus, alterations in the activities of other important enzymes such as CYP3A. The data also suggest that the genotype/phenotype probes can be used to optimize the clinical treatment of patients with advanced disease states.
authors.affiliation: University of Leicester, Oncology Department, Hodgkin Building, PO Box 138, Lancaster Road, Leicester, LE1 9HN, UK. mlw15@le.ac.uk
authors.forename: Marion L
authors.initials: ML
authors.lastname: Williams
authors.forename: Irving W
authors.initials: IW
authors.lastname: Wainer
mesh_terms: D000818:Animals; D018450:Disease Progression; D005838:Genotype; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010641:Phenotype
chemical_list: D004364:Pharmaceutical Preparations