Evaluation of ketoprofen (R, S and R/S) phototoxicity by a battery of in vitro assays

The various enantiomers of ketoprofen (S and R) and its racemic form (R/S) exhibited comparable phototoxicities when examined by the following in vitro test systems: (a) effects of pre-irradiated drugs on cultured hepatocytes; (b) co-irradiation of the drugs with hepatocytes or fibroblasts; (c) photohaemolysis sensitized by the various ketoprofen stereoisomers; (d) drug-photosensitized formation of linoleic acid hydroperoxides. Inhibition of photohaemolysis and photodynamic lipid peroxidation by butylated hydroxyanisole and reduced glutathione suggests that the phototoxicity of ketoprofen is associated with a radical chain (type I) peroxidation of membrane lipids, leading to cell lysis. In view of the above results it could be advantageous to use the pharmacologically active S(+) enantiomer instead of the R/S form, since the lower doses required would result in a diminished phototoxic potential.