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[Hepatoxicity caused by flutamide increased by hypotensive situation?]
N Serrano Hernández1, F García López, J Fedriani Gorria
1Unidad de Medicina Intensiva, Hospital General, Albacete.
Abstract:
We describe a 76-year-old male patient who developed a life-threatening acute hepatotoxicity possibly caused by flutamide, an antiandrogen drug given during the previous 10 months, in the scenario of a brief moderate hypotension secondary to atrial flutter. There was a sudden increase of liver enzyme levels AST = 4.521 IU/L, ALT = 1.716 IU/L (normal values 0-37 and 0-40 respectively), prothrombin activity decreased to 16%, and also felt the platelet count, with significant haemorrhages. We hypothesize this was triggered as a consequence of the transient diminished supply of oxygen to the subclinically flutamide-damaged hepatocytes by the well-known mechanism of the cytochrome P450 (3A and 1A)-mediated formation of electrophilic metabolites, and the inhibitory effect of flutamide on mitochondrial respiration and ATP formation.