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 followi ng in vitro test systems: (a) effects of pre-irradiated drugs on cultu red hepatocytes; (b) co-irradiation of the drugs with hepatocytes or f ibroblasts; (c) photohaemolysis sensitized by the various ketoprofen s tereoisomers; (d) drug-photosensitized formation of linoleic acid hydr operoxides. Inhibition of photohaemolysis and photodynamic lipid perox idation by butylated hydroxyanisole and reduced glutathione suggests t hat the phototoxicity of ketoprofen is associated with a radical chain (type I) peroxidation of membrane lipids, leading to cell lysis. In v iew of the above results it could be advantageous to use the pharmacol ogically active S(+) enantiomer instead of the R/S form, since the low er doses required would result in a diminished phototoxic potential.