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Published on: August 24, 2013
Genotype/phenotype comparisons: a probe for the effect of disease progression on drug metabolism
Marion L Williams1, Irving W Wainer
1University of Leicester, Oncology Department, Hodgkin Building, PO Box 138, Lancaster Road, Leicester, LE1 9HN, UK. mlw15@le.ac.uk
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.
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