Hyperlipidaemia alone and in combination with acidosis can increase the incidence and severity of statin-induced myotoxicity
The association of lipophilic statins with plasma lipoproteins in the presence of disturbed acid-base balance can modify the pharmacokinetics and tissue distribution of these drugs, resulting in alteration in their efficacy and toxicity profiles. The purpose of this study is to elucidate the role of...
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Elsevier
2017
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| Online Access: | https://eprints.nottingham.ac.uk/39896/ |
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| author | Taha, Dhiaa A. Zgair, Atheer Lee, Jong Bong de Moor, Cornelia H. Barrett, David A. Bruce, Kimberley D. Sungelo, Mitchell Eckel, Robert H. Gershkovich, Pavel |
| author_facet | Taha, Dhiaa A. Zgair, Atheer Lee, Jong Bong de Moor, Cornelia H. Barrett, David A. Bruce, Kimberley D. Sungelo, Mitchell Eckel, Robert H. Gershkovich, Pavel |
| author_sort | Taha, Dhiaa A. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | The association of lipophilic statins with plasma lipoproteins in the presence of disturbed acid-base balance can modify the pharmacokinetics and tissue distribution of these drugs, resulting in alteration in their efficacy and toxicity profiles. The purpose of this study is to elucidate the role of hyperlipidaemia alone or in combination with acidosis/alkalosis in the development and potentiation of statin-induced myotoxicity. Statins association with plasma lipoproteins was examined under conditions of physiological and altered pH levels. The effect of this association on cellular uptake and myotoxicity of statins was also assessed at different pH levels using C2C12 cells that overexpress lipoprotein lipase. Lipophilic simvastatin displayed considerable association with the non-polar lipoprotein fractions (triglyceride-rich lipoproteins and Low-density lipoprotein). This association contributed to increased cellular uptake of simvastatin by C2C12 cells through lipoprotein lipasemediated process, resulting in enhanced muscle toxicity in hyperlipidaemic conditions. Furthermore, a combination of low pH environment (representing acidosis) and hyperlipidaemia increased the association of simvastatin with plasma lipoproteins causing potentiation of cellular uptake and myotoxicity of this drug. Comorbidities such as hyperlipidaemia, especially when coincident with acidosis, can enhance statin-associated muscle toxicity, and therefore require extra caution by prescribing clinicians. Hydrophilic rather than lipophilic statins could be a preferable choice in this patient population. |
| first_indexed | 2025-11-14T19:40:05Z |
| format | Article |
| id | nottingham-39896 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:40:05Z |
| publishDate | 2017 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-398962020-05-04T18:39:56Z https://eprints.nottingham.ac.uk/39896/ Hyperlipidaemia alone and in combination with acidosis can increase the incidence and severity of statin-induced myotoxicity Taha, Dhiaa A. Zgair, Atheer Lee, Jong Bong de Moor, Cornelia H. Barrett, David A. Bruce, Kimberley D. Sungelo, Mitchell Eckel, Robert H. Gershkovich, Pavel The association of lipophilic statins with plasma lipoproteins in the presence of disturbed acid-base balance can modify the pharmacokinetics and tissue distribution of these drugs, resulting in alteration in their efficacy and toxicity profiles. The purpose of this study is to elucidate the role of hyperlipidaemia alone or in combination with acidosis/alkalosis in the development and potentiation of statin-induced myotoxicity. Statins association with plasma lipoproteins was examined under conditions of physiological and altered pH levels. The effect of this association on cellular uptake and myotoxicity of statins was also assessed at different pH levels using C2C12 cells that overexpress lipoprotein lipase. Lipophilic simvastatin displayed considerable association with the non-polar lipoprotein fractions (triglyceride-rich lipoproteins and Low-density lipoprotein). This association contributed to increased cellular uptake of simvastatin by C2C12 cells through lipoprotein lipasemediated process, resulting in enhanced muscle toxicity in hyperlipidaemic conditions. Furthermore, a combination of low pH environment (representing acidosis) and hyperlipidaemia increased the association of simvastatin with plasma lipoproteins causing potentiation of cellular uptake and myotoxicity of this drug. Comorbidities such as hyperlipidaemia, especially when coincident with acidosis, can enhance statin-associated muscle toxicity, and therefore require extra caution by prescribing clinicians. Hydrophilic rather than lipophilic statins could be a preferable choice in this patient population. Elsevier 2017-03-30 Article PeerReviewed Taha, Dhiaa A., Zgair, Atheer, Lee, Jong Bong, de Moor, Cornelia H., Barrett, David A., Bruce, Kimberley D., Sungelo, Mitchell, Eckel, Robert H. and Gershkovich, Pavel (2017) Hyperlipidaemia alone and in combination with acidosis can increase the incidence and severity of statin-induced myotoxicity. European Journal of Pharmaceutical Sciences, 100 . pp. 163-175. ISSN 1879-0720 Acidosis Chylomicrons Hyperlipidemia Lipoproteins Myotoxicity Statins http://www.sciencedirect.com/science/article/pii/S0928098717300301 doi:10.1016/j.ejps.2017.01.018 doi:10.1016/j.ejps.2017.01.018 |
| spellingShingle | Acidosis Chylomicrons Hyperlipidemia Lipoproteins Myotoxicity Statins Taha, Dhiaa A. Zgair, Atheer Lee, Jong Bong de Moor, Cornelia H. Barrett, David A. Bruce, Kimberley D. Sungelo, Mitchell Eckel, Robert H. Gershkovich, Pavel Hyperlipidaemia alone and in combination with acidosis can increase the incidence and severity of statin-induced myotoxicity |
| title | Hyperlipidaemia alone and in combination with acidosis can increase the incidence and severity of statin-induced myotoxicity |
| title_full | Hyperlipidaemia alone and in combination with acidosis can increase the incidence and severity of statin-induced myotoxicity |
| title_fullStr | Hyperlipidaemia alone and in combination with acidosis can increase the incidence and severity of statin-induced myotoxicity |
| title_full_unstemmed | Hyperlipidaemia alone and in combination with acidosis can increase the incidence and severity of statin-induced myotoxicity |
| title_short | Hyperlipidaemia alone and in combination with acidosis can increase the incidence and severity of statin-induced myotoxicity |
| title_sort | hyperlipidaemia alone and in combination with acidosis can increase the incidence and severity of statin-induced myotoxicity |
| topic | Acidosis Chylomicrons Hyperlipidemia Lipoproteins Myotoxicity Statins |
| url | https://eprints.nottingham.ac.uk/39896/ https://eprints.nottingham.ac.uk/39896/ https://eprints.nottingham.ac.uk/39896/ |