Metabolism and Excretion of the 5-HT1D antagonist ~(14)CCP-448,187 in Humans: Determination of the Site of Hydroxylation of the Major Fecal Metabolite and Structural Characterization of the Novel Cyclized Indole Major Circulating Metabolite by ~(1)HLC-NMR and Chemical Approaches

摘要

CP-448,187 was extensively metabolized and only a small amount of unchanged drug was found in urine and feces. Total recovery of the administered dose was 78.9 +- 5.6. Approximately 57.9 +- 4.2percent and 21.0 +- 1.9percent (mean +- SD) of the administered radioactive dose was excreted in feces and urine, respectively (average of 6 human subjects). The major component of drug related material in the excreta was in the feces and was unambiguously identified as the 5-OH-CP-448,187 metabolite (M2) and accounted approximately for 34.4percent of the administered dose. Additionally, the major human circulating metabolite was identified unambiguously as the novel cyclized indole metabolite of CP-448,187 (M10A) using 1H-NMR and chemical approaches and accounted for approx65percent of the total radioactivity (average of 6 human subjects).