Enzymes and conjugation

Because of the rare and unpredictable nature of hepatobihary reactions to terbinafine, the mechanism of hepatotoxicity has been hypothesized to be either immunological or metabolically mediated. A potentially toxic reactive metabolite of terbinafine, 7,7-dimethylhept-2-ene-4-jmal (TBF-A), the A-dealkylation product of terbinafine, has been identified in vitro (43). The authors speculated that this allylic aldehyde metabolite, formed by hver enzymes and conjugated with glutathione, would be transported across the canalicular membrane of hepatocytes and concentrated in the bile. The reactive monoglutathione conjugate could bind to hepatobiliary proteins and cause direct toxicity. Alternatively, it could modify canahcular proteins and lead to an immune-mediated reaction, causing cholestatic dysfunction. 

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