Prediction of atorvastatin plasmatic concentrations in healthy volunteers using integrated pharmacogenetics sequencing

Pharmacogenomics. 2017 Jan;18(2):121-131. doi: 10.2217/pgs-2016-0072. Epub 2016 Dec 15.

Abstract

Aim: To use variants found by next-generation sequencing to predict atorvastatin plasmatic concentration profiles (AUC) in healthy volunteers.

Subjects & methods: A total of 60 healthy Mexican volunteers were enrolled in this study. We used variants with a predicted functional effect across 20 genes involved in atorvastatin metabolism to construct a regression model using a support vector approach with a radial basis function kernel to predict AUC refining it afterwards in order to explain a greater extent of the variance.

Results: The final support vector regression model using 60 variants (including six novel variants) explained 94.52% of the variance in atorvastatin AUC.

Conclusion: An integrated analysis of several genes known to intervene in the different steps of metabolism is required to predict atorvastatin's AUC.

Keywords: Next-Gen sequencing; atorvastatin; pharmacokinetics.

MeSH terms

  • Adolescent
  • Adult
  • Atorvastatin / blood*
  • Atorvastatin / pharmacokinetics
  • Forecasting
  • Healthy Volunteers
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / blood*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics
  • Male
  • Mexico / epidemiology
  • Middle Aged
  • Pharmacogenetics / methods*
  • Pharmacogenomic Variants / genetics*
  • Young Adult

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Atorvastatin