Pharmacogenetic Dose Modeling Based on CYP2C19 Allelic Phenotypes.

ABSTRACT: Pharmacogenetic variability in drug metabolism leads to patient vulnerability to side effects and to therapeutic failure. Our purpose was to introduce a systematic statistical methodology to estimate quantitative dose adjustments based on pharmacokinetic differences in pharmacogenetic subgroups, addressing the concerns of sparse data, incomplete information on phenotypic groups, and heterogeneity of study design. Data on psychotropic drugs metabolized by the cytochrome P450 enzyme CYP2C19 were used as a case study. CYP2C19 activity scores were estimated, while statistically assessing the influence of methodological differences between studies, and used to estimate dose adjustments in genotypic groups. Modeling effects of activity scores in each substance as a population led to prudential p

SUBMITTER: Stingl JC 

PROVIDER: S-EPMC9781550 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature