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Current Organic Chemistry

Editor-in-Chief

ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

Review Article

Transformations of Statins: Effect of Light and pH

Author(s): Donata Pluskota-Karwatka* and Marcin Hoffmann

Volume 22, Issue 19, 2018

Page: [1926 - 1939] Pages: 14

DOI: 10.2174/1385272822666180913112356

Price: $65

Abstract

Statins are popular drugs widely prescribed in Europe and the USA to control hypercholesterolemia and to prevent cardiovascular diseases. Among these drugs, synthetic statins possess the ability to absorb UV radiations in both UVA and UVB ranges.

Light can induce drugs degradation leading to essential changes in their pharmaceutical properties and even to the loss of therapeutic activity, and/or to the formation of deleterious photoproducts. Drugs which exhibit photochemical reactivity may elicit undesired adverse effects. Knowledge of mechanisms involved in the molecular basis of these effects origin is of great importance for understanding chemical nature of occurring processes and their biological and medicinal implications, as well as for evaluating the photobiological risk associated with therapy in which drugs sensitive to light are involved.

In this work, photophysical properties and photochemical behaviour of synthetic statins were reviewed, and findings regarding photodegradation mechanisms were summarised and critically discussed resulting in the revision of some previously reported facts as well as in proposing new schemes for the transformations of this important group of organic compounds. Moreover, possible biological consequences of statins photoinstability were also discussed.

Besides the effect of light, statins’ sensitivity to pH and resulting implications were discussed. Statins undergo pH-dependent interconversion between their pharmacologically active hydroxy acid and inactive lactone forms and it was shown that for both forms, drugs’ interactions should be considered. Knowledge of the statins interconversion mechanisms is important for understanding how differences in the structures of their molecules can affect the activity of the drug at the molecular level and can have an impact on designing more effective novel and safe drugs.

Keywords: Statins, rosuvastatin, pitavastatin, atorvastatin, fluvastatin, HMG-CoA reductase inhibitors, lactonisation, drugs’ interactions, photosensitizers.

Graphical Abstract

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