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IRREVERSIBLE BINDING OF CHLORDIAZEPOXIDE TO HUMAN PLASMA PROTEIN INDUCED BY UV‐A RADIATION
Author(s) -
Bakri A.,
Henegouwen G. M. J. Beijersbergen,
Sedee A. G. J.
Publication year - 1986
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1986.tb03583.x
Subject(s) - chlordiazepoxide , oxaziridine , chemistry , phototoxicity , irradiation , kinetics , covalent bond , biophysics , stereochemistry , biochemistry , pharmacology , organic chemistry , in vitro , physics , quantum mechanics , diazepam , nuclear physics , biology , medicine
— 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.