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Abstract
1. The metabolic disposition of the anti-ulcer agent geranylgeranylacetone (GGA) was examined in rats.
2. Urinary metabolites were isolated and identified by mass spectrometry and 1H n.m.r. studies. Three metabolites were dicarboxylic acids with chain lengths of C7, C9 and C11 and accounted for 31.6%, 14.8% and 5.3%, respectively, of the radioactivity excreted in the urine 24 h after oral administration of 14C-GGA.
3. The metabolites produced by the incubation of GGA with liver microsomes in the presence of an NADPH-generating system were identified as an ω-hydroxylated derivative of GGA and its ketone-reduced form.
4. The characterization of GGA metabolites indicates that the metabolic pathway of GGA in rats involves ω-oxidation (possibly via the corresponding carboxylic acid) and successive β-oxidation processes.