High-Performance Liquid Chromatographic Assay of the Aldose Reductase Inhibitor Spiro-(2-fluoro-9h-fluorene-9,4′-imidazolidine)-2′,5′-dione (AL01567) in Plasma and Urine and Its Pharmacokinetics in Humans

Park, Young Han; McCue, Bette A.; Dobbs, R. E.; York, Billie M.; Brazzell, Romulus K.

doi:10.1002/jps.2600770709

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1991

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“…In vivo studies have also demonstrated that AL01567 can retard the development of cataracts and neuropathy in streptozotocin-induced diabetic rats and in galactosaemic rats, presumably by preventing sorbitol and galactitol (dulcitol) accumulation in tissue (Chandler et al, 1982;Griffin et al, 1984Griffin et al, , 1987. The pharmacokinetics of AL01567 have been studied in various species including man (Brazzell et al, 1990;Park et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

Metabolism of the aldose reductase inhibitor ALO1567 in man.

Hudson

Barker

et al. 1991

Brit J Clinical Pharma

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1 The metabolism of the aldose reductase inhibitor, AL01567, 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 AL01567 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 AL01567 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 AL01567. Most subjects having higher AL01567 plasma concentrations showed higher ratios.

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Section: Introductionmentioning

confidence: 99%