Atorvastatin's Phototoxicity Probed

Medical researchers announced on Nov. 9 that statins, drugs known for reducing blood levels of cholesterol, could cut the risk of heart attack and stroke in half for people with low cholesterol and high levels of a particular protein (N. Engl. J. Med. 2008, 359, 2195). Although statins appear to have many benefits, some poorly understood and potentially adverse reactions that can take place in vivo. For example, some patients taking atorvastatin have reported skin sensitivity to the sun. Previous work with atorvastatin shows that exposing an aqueous solution of the drug to natural sunlight oxidizes its pyrrole ring, forming a phenanthrene derivative. Now, Miguel A. Miranda at Polytechnic University of Valencia, in Spain, and colleagues have used spectroscopy techniques to better understand this photochemical mechanism (Chem. Res. Toxicol., DOI: 10.1021/tx800294z). After confirming that exciting atorvastatin with light generates a phenanthrene-like photoproduct (shown), the scientists demonstrated that the photoproduct can lead to formation of tissue-damaging singlet oxygen. The researchers suggest that exchanging the substituents of atorvastatin's pyrrole ring would prevent formation of the photoproduct, but they did not test how the changes would affect the drug's therapeutic activity.