Photopharmacology of the Tranquilizer Chlordiazepoxide in Relation to Its Phototoxicity

This study demonstrates that photobiological effects by exogenous molecules are not per se restricted to the skin. As an example the photopharmacology of chlordiazepoxide (e.g. LibriumR) was studied. Rats being exposed to UV‐A after administration of 14C2 labeled chlordiazepoxide (CDZ) showed a marked change in the pattern of urinary metabolites; the quantity of metabolites without N4‐oxide function increased, whereas that of compounds with N4‐oxide function decreased. Covalent binding to organ tissue of especially liver and skin of the irradiated rats was found. This would mean that in the irradiated rats oxaziridines which may also react with tissue of the inner organs are formed from CDZ and its N4‐oxymetabolites. Further, the combination of light and CDZ leads to a 30% decrease in weight of the liver, indicating liver damage. This is also supported by the percentage of conjugated urinary metabolites being 1.5–2.5 times lower than in the non‐irradiated CDZ‐treated rats, possibly caused by a decrease of enzymatic activity. The administration of CDZ‐oxaziridine to non‐irradiated rats provoked the same effects, such as a decrease of the weight of the liver comparable to that of irradiated CDZ‐treated rats. On the other hand the combination of light and treatment with N4‐desoxy CDZ did not have any effect, as expected.