%0 Journal Article %A S. Cyrus Khojasteh-Bakht %A John P. O'Donnell %A Hassan G. Fouda %A Michael J. Potchoiba %T METABOLISM, PHARMACOKINETICS, TISSUE DISTRIBUTION, AND EXCRETION OF [14C]CP-424391 IN RATS %D 2005 %R 10.1124/dmd.104.001065 %J Drug Metabolism and Disposition %P 190-199 %V 33 %N 1 %X CP-424391, 2-amino-N-[3aR-benzyl-2-methyl-3-oxo-2,3,3a,4,6,7-hexahydro-pyrazolo[4,3-c]pyridin-5-yl)-1R-benzyloxymethyl-2-oxoethyl]-isobutyramide, is an orally active growth hormone secretagogue currently being developed. In this study, we investigated the metabolic fate and disposition of radiolabeled CP-424391 in rats. Following 15 mg/kg single oral administration to Sprague-Dawley rats, 91% of the radiolabeled dose was recovered. Feces was the major route of excretion: 77% of the dose recovered in feces of the female rat and 84% in the male. Excretion in the urine was 15% in the female rat compared with 7% in the male. Both fecal and urinary metabolic profiles were consistent in both genders. The metabolic pathways of CP-424391 were oxidation at the benzyl group of the O-benzylserine moiety, N-demethylation of pyrazolidine, and/or O-debenzylation. In circulation, CP-424391 was absorbed within the first hour to an average apparent Cmax of 1.44 μg/ml. CP-424391 accounts for about 40% of radioactivity area under the plasma concentration-time curve and Cmax in circulation. The plasma terminal elimination half-life of CP-424391 was 2.4 h and for total radioactivity was 2.8 h. The radioactivity was widely distributed in all tissues except for the central nervous system. [14C]CP-424391 radioactivity was eliminated from most tissues by 9 h with the exception of liver, skin, and uvea. By 168 h, [14C]CP-424391 radioactivity remained localized only in the uvea. The American Society for Pharmacology and Experimental Therapeutics %U https://dmd.aspetjournals.org/content/dmd/33/1/190.full.pdf