Atorvastatin population pharmacokinetics in a real‐life setting: Influence of genetic polymorphisms and association with clinical response
(2021) Clinical and Translational Science (Print) — (2021)
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- Abstract
- The purpose of this study was to investigate the potential clinical relevance of estimating the apparent clearance (CL/F) of atorvastatin through population pharmacokinetics (popPK) modeling with samples collected in a real-life setting in a cohort of ambulatory patients at risk of cardiovascular disease by using an opportunistic sampling strategy easily accessible in clinical routine. A total of 132 PK samples at a maximum of 3 visits were collected in the 70 included patients. The effects of demographic, genetic and clinical covariates were also considered. With the collected data, we developed a two-compartments PopPK model that allowed estimating atorvastatin CL/F relatively precisely and considering the genotype of the patient for SLCO1B1 c.521T>C SNP. Our results indicate that the estimation of the apparent clearance of atorvastatin through our PopPK model might help in identifying patients at risk of myalgia. Indeed, we showed that a patient presenting a CL/F lower than 414.67 L.h-1 is at risk of suffering from muscle discomfort. We also observed that the CL/F was correlated with the efficacy outcomes, suggesting that a higher CL/F is associated with a better drug efficacy (i.e. a greater decrease in total and LDL-cholesterol levels). In conclusion, our study demonstrates that PopPK modeling can be useful in daily clinics to estimate a patient' atorvastatin clearance. Notifying the clinician with this information can help in identifying patients at risk of myalgia and gives indication about the potential responsiveness to atorvastatin therapy.
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Stillemans, G., Paquot, A., Muccioli, G., Hoste, E., Panin, N., Åsberg, A., Balligand, J.-L., Haufroid, V., & Elens, L. (2021). Atorvastatin population pharmacokinetics in a real‐life setting: Influence of genetic polymorphisms and association with clinical response. Clinical and Translational Science (Print). Published. https://doi.org/10.1111/cts.13185 (Original work published 2021)