Is Genetic Variability in Carboxylesterase-1 and Carboxylesterase-2 Drug Metabolism an Important Component of Personalized Medicine?

Is Genetic Variability in Carboxylesterase-1 and Carboxylesterase-2 Drug Metabolism an Important Component of Personalized Medicine? Xenobiotica. 2019 Oct 11;:1-21 Authors: Laizure SC, Parker RB Abstract The carboxylesterase drug hydrolysis pathway has been used extensively to improve the oral availability of drugs under the assumption that the high capacity and low substrate specificity of hydrolytic enzymes would ensure rapid, complete, and consistent conversion of prodrugs to their active metabolite. However, a growing body of literature indicates that drug hydrolysis is usually catalyzed by one primary enzyme, either carboxylesterase-1 or carboxlylesterase-2, and that there is wide variability in enzyme activity affecting the metabolism of prodrugs to their active metabolites. This review identifies carboxylesterase substrates and describes our current understanding of the influence of genetic polymorphisms on substrate disposition and clinical effects. Several polymorphisms are described in the literature and included in the personalized medicine database PharmGKB, but there are no carboxylesterase genotypes referenced in Food and Drug Administration approved drug labeling. The limited validation of metabolic pathways for drugs undergoing hydrolysis, and the small number of studies evaluating genotype-drug interactions confirm that this is an emerging field of drug metabolism research. The dependence of prodrugs, many with low t...
Source: Xenobiotica - Category: Research Authors: Tags: Xenobiotica Source Type: research