Study of atorvastatin cellular transport: from fundamental to translational approaches
(2024)
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- Abstract
- This thesis investigates the intramuscle atorvastatin (ATV) pharmacokinetics contributing to statin-related myotoxicities and non-adherence to cardiovascular disease treatment. The research explores two axes: a fundamental axis examining the impact of overexpressing transporters (ABCC1 and SLCO2B1) and single nucleotide polymorphisms (SNPs) on ATV transport in HEK293 models, and a translational axis evaluating transporters’ implication in primary skeletal myotubes. Results show that ATV is a substrate for both transporters, with both SNPs decreasing ATV intracellular accumulation. Experiments in primary myotubes reveal a high inter-individual variability. Repression of ABCC1/ABCG2 expression increases ATV accumulation whereas reducing SLCO1B1/SLCO2B1 expression has a moderate effect on ATV accumulation. These findings highlight potential insights into differential responses and drug interactions in ATV treatment.
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Citations
Hoste, E. (2024). Study of atorvastatin cellular transport: from fundamental to translational approaches. https://hdl.handle.net/2078.5/233822