IRREVERSIBLE BINDING OF NITROFURANTOIN TO SKIN AND TO PLASMA PROTEINS OF UV-A EXPOSED RATS

Abstract— Allergic reactions to the widely applied urinary tract disinfectant nitrofurantoin (NFT) often concern the skin. They are probably mediated by a NFT-protein adduct. which has been suggested to result from incomplete nitro-reduction during metabolism. In this study it was investigated whether photoactivation of NFT in rats, upon exposure to UV-A, leads to formation of adducts between the drug and biomacromolecules. Rats were given p.o. doses of [¹⁴C]-NFT, and some were exposed to UV-A. More irreversible binding was found in skin of the back (both in dermis and in epidermis). tail, ears, eyes, plasma proteins, and spleen of light-exposed rats compared to those kept in the dark. This photobinding increased (up to ∼0.6 nmol/mg protein =∼25 nmol/g tissue) with dose and light-intensity. When rats were kept at 32°C, instead of 22°C during NFT/UV-A treatment, even more irreversible binding was observed; this is probably caused by an increased dermal blood flow. Under these conditions, irreversibly bound radioactivity was even found in kidney, lung and liver. Irreversible binding in these inner organs is explained by systemic distribution of radioactivity, photobound to plasma proteins. Photodecomposition of NFT in the skin, followed by reaction of photoproducts with (cellular) biomacromolecules may explain some of the skin rashes and other (allergic) reactions reported for this drug.