Mechanisms of skin rashes from fenbufen

Fenbufen-induced skin rash was investigated by determining the metabolism of the drug to reactive products. At least five lipophilic products (unidentified), the active metabolite of this drug, biphenyl acetic acid (BPAA), and a gamma-hydroxylated derivative (gamma-hydroxy[1,1'-biphenyl]-4-butanoic acid) were identified in keratinocytes in vitro and in skin of rats and guinea pigs in vivo. The gamma-OH derivatives of BPAA and fenbufen were recovered from papain digests of the prior ether-extracted keratinocyte proteins. Fenbufen and its gamma-OH metabolite stimulated the production of interleukin-1 from keratinocytes exposed to UV radiation but BPAA did not. Inflammatory reactions from fenbufen may therefore, arise from production of its metabolites which yield IL-1 upon exposure to UV radiation.