Statin induced myotoxicity: The lactone forms are more potent than the acid forms in human skeletal muscle cells in vitro
Autor: | I B Skottheim, Ane Gedde-Dahl, Kjersti Hoel, Anders Åsberg, Solmaz Hejazifar |
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Rok vydání: | 2008 |
Předmět: |
Simvastatin
Indoles Statin Satellite Cells Skeletal Muscle Cell Survival medicine.drug_class Atorvastatin Muscle Fibers Skeletal Pharmaceutical Science In Vitro Techniques Biology Pharmacology Fatty Acids Monounsaturated Lactones Structure-Activity Relationship Drug Stability medicine Humans Pyrroles cardiovascular diseases Fluvastatin Muscle Skeletal Cells Cultured Pravastatin chemistry.chemical_classification Dose-Response Relationship Drug Molecular Structure nutritional and metabolic diseases Skeletal muscle medicine.anatomical_structure Microscopy Fluorescence chemistry Heptanoic Acids HMG-CoA reductase biology.protein lipids (amino acids peptides and proteins) Hydroxymethylglutaryl-CoA Reductase Inhibitors Acids Lactone medicine.drug |
Zdroj: | European Journal of Pharmaceutical Sciences. 33:317-325 |
ISSN: | 0928-0987 |
Popis: | Statins exist in both acid and lactone forms in vivo. High plasma levels of the lactone forms have been observed in patients with statin induced myopathy. In the present study, the hypothesis that lactone forms have a higher potency of inducing myotoxicity as compared to acid forms was investigated. Primary human skeletal muscle cells were incubated with increasing concentrations of lactone and acid forms of atorvastatin, fluvastatin, pravastatin and simvastatin. Following incubation, living myotubes were quantified by fluorescence staining. Atorvastatin lactone showed a 14-fold, fluvastatin lactone a 26-fold, pravastatin lactone a 23-fold, and simvastatin lactone a 37-fold higher potency to induce myotoxicity compared to their corresponding acid forms. Thus, for the four different statins the present study shows a significantly higher potency of the lactone forms, than the respective acid forms, to induce myotoxicity in human skeletal muscle cells in vitro. These results clearly indicate the need to differentiate between acid and lactone forms in future investigation of statin myotoxicity. |
Databáze: | OpenAIRE |
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