IRREVERSIBLE BINDING OF CHLORDIAZEPOXIDE TO HUMAN PLASMA PROTEIN INDUCED BY UV‐A RADIATION

Abstract

Abstract— In view of the phototoxicity of chlordiazepoxide (Librium ® ) the kinetics of the reaction in the presence of plasma proteins was studied for chlordiazepoxide upon UV‐A irradiation and for its oxaziridine in the dark. Two different methods were used to determine the extent of irreversible binding to protein (up to ∼ 50% was found for both situations). Kinetic data support the conclusion that the formation of oxaziridine from photoexcited chlordiazepoxide is the basic event making chlordiazepoxide phototoxic. The half life of oxaziridine is about 30 min even in the presence of a high concentration of plasma proteins, is in agreement with previous in vivo results, showing covalent binding not only to biomolecules of the UV‐A irradiated skin but also to those of inner organs, e.g. liver and kidneys.