Precision management of atorvastatin: Cross-sectional analysis of genetic polymorphisms

Razan Ibrahim1, Mohanad Odeh2, Eyad Mallah1

  • 1Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, Jordan.

Insights

This study developed a reliable LC-MS/MS method to measure atorvastatin in plasma. Genetic variants like CYP2D6-4 significantly impact atorvastatin levels, supporting personalized hyperlipidemia treatment.

Area of Science:

  • Pharmacology
  • Clinical Chemistry
  • Genetics

Background:

  • Hyperlipidemia is a key risk factor for cardiovascular diseases.
  • Genetic variants (e.g., CYP2D6-4) influence atorvastatin metabolism and effectiveness.
  • Personalized drug monitoring is crucial for managing hyperlipidemia.

Purpose of the Study:

  • Develop and validate an LC-MS/MS method for quantifying atorvastatin in human plasma.
  • Investigate the impact of genetic polymorphisms, specifically CYP2D6-4, on atorvastatin plasma concentrations.
  • Enhance personalized therapeutic drug monitoring and lipid profile management.

Main Methods:

  • Quantification of atorvastatin using Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS).
  • Genotyping using Polymerase Chain Reaction (PCR)-based methods.
  • Statistical analysis to correlate plasma atorvastatin levels with genetic variants.

Main Results:

  • The LC-MS/MS method demonstrated high accuracy, precision, linearity, and stability.
  • Higher atorvastatin plasma concentrations were associated with the CYP2D6-4 genetic variant.
  • The analytical method was validated for reliable clinical sample measurement.

Conclusions:

  • A robust LC-MS/MS method for atorvastatin quantification in plasma was successfully developed and validated.
  • The strong link between CYP2D6-4 and atorvastatin levels underscores the importance of pharmacogenetic dosing.
  • Integrating pharmacogenetics, particularly in the Jordanian population, can improve atorvastatin therapy safety, efficacy, and individualization.
Abstract

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