(1S,5R)-4-((E)-3,4-dihydroxy-5-methoxystryryl)-6,6-dimethylbicylco[3.1.1]hept-3-en-2-one\n(SP-8356) is a novel (1S)-(-)-verbenone derivative that is currently in preclinical development for\nthe treatment of ischemic stroke and atherosclerosis. This report aimed at characterization of the\nmetabolism and pharmacokinetic properties of SP-8356. Following intravenous dose in rats and dogs,\nplasma concentrations of SP-8356 declined rapidly with high clearance (CL) and short half-life; after\noral administration in both species, its plasma levels were below the quantitation limit. Fourteen\ncirculating metabolites, formed by mono-oxygenation, demethylation, glucuronidation, catechol\nO-methylation, sulfation and oxidation (bioactivation) followed by glutathione (GSH) conjugation,\nwere tentatively identified in both species. Urinary excretion of SP-8356 appeared to be minimal in\nrats, compared to its metabolites..............
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