Metabolism of the aldose reductase inhibitor ALO1567 in man.

Abstract

1. The metabolism of the aldose reductase inhibitor, ALO1567, was studied in man. The major biotransformation pathway was aromatic hydroxylation followed by glucuronide conjugation. 2. Hydroxylation occurred at several positions on the fluorene ring. The major metabolite was identified as the 7‐hydroxy analogue of ALO1567 and three minor metabolites were characterized as positional isomers of the 7‐hydroxy metabolite. 3. Oxidative defluorination and metabolism on the hydantoin ring were also indicated as minor pathways. 4. The capacity of normal subjects to oxidize ALO1567 was indicated by the urinary ratio of the parent drug to the 7‐hydroxy metabolite after daily oral administration of 100 mg and 200 mg of ALO1567. Most subjects having higher ALO1567 plasma concentrations showed higher ratios.