3'-tert-Butyl-3'-N-tert-butyloxycarbonyl-4-deacetyl-3'-dephenyl-3'-N-debenzoyl-4-O-methoxy-paclitaxel (BMS-275183) is a taxane analog that has the potential for oral use in the treatment of various types of cancer. In this study, the metabolism and excretion of [(14)C]BMS-275183 were evaluated after a single oral administration of [(14)C]BMS-275183 to rats and dogs (15 and 1 mg/kg, respectively). To aid metabolite identification by mass spectrometry (MS), a stable labeled (phenyl-(13)C(6)) BMS-275183 was included in 1:1 ratio of (13)C(6)/(12)C in the dose administration. Fecal excretion was the major route of elimination for [(14)C]BMS-275183 in both species (85-86 and <9% of the dose in feces and urine, respectively). The highest radioactivity in plasma was observed at 1 h postdose, suggesting rapid absorption of the drug in both species. The total radioactivity in plasma was measurable up to 24 h postdose. Metabolites were identified by liquid chromatography-MS and/or NMR spectroscopy. [(14)C]BMS-275183 was the prominent component in rat and dog plasma and was detected up to 24 h along with various oxidative and hydrolytic metabolites. [(14)C]BMS-275183 was extensively metabolized in both species, forming mainly oxidative metabolites, and unchanged parent drug accounted for <3.5% of the administered dose in urine and feces. The prominent metabolites resulted from oxidation of the tert-butyl groups on the side chain and further oxidation and cyclization of the tert-butylhydroxylated metabolites. A total of 30 oxidative metabolites including M13, a prominent ester cleavage metabolite, were identified in rat and dog samples.