Mechanism of tetracycline phototoxicity.

Studies were made to determine factors important in the phototoxicity mechanism of 7 clinically used tetracyclines (TC). The clinical phototoxicity, the rates of photochemical degradation, and the in vitro phototoxicity of the TCs were qualitatively but not quantitatively correlated. Phototoxicity in vitro was partially oxygen-dependent and possibly singlet oxygen is involved. The contribution of photoproducts to the phototoxic process may be the basis for the reported differences between the in vivo action spectrum and the absorption spectrum of demethylchlorotetracycline. A mechanistic model for in vivo phototoxicity is proposed where the absorption of UVA radiation by TC leads to at least two main processes: (i) photosensitization by the drug of biologic molecules to cause phototoxicity; (ii) production of one or more photoproducts which photosensitize by absorption of visible radiation.