Abstract
The excretion and metabolism of a 2-ethynylbenzenealkanamine analog, antihypertensive RWJ-26240 (McN-5691), in beagle dogs was investigated. Recoveries of total radioactivity in urine and feces in the 7 days after oral administration of14C-RWJ-26240 (6 mg/kg dose) were 2.8% and 96.8% of the radioactive dose, respectively. Representative plasma, urine, and fecal samples were pooled and purified for metabolite profiling, isolation, and identification. Unchanged RWJ-26240 (<19% of the dose) plus 12 metabolites were isolated and identified from these samples using chromatography (TLC, HPLC), spectroscopy (NMR, MS), and derivatization techniques. Unchanged RWJ-26240 plus identified metabolites accounted for >75% of the sample radioactivity in plasma and feces. The formation of RWJ-26240 metabolites can be depicted by the following proposed pathways: 1) N-demethylation, 2)O-demethylation, 3) phenyl hydroxylation, and 4)N-dealkylation. The first three pathways appeared to be quantitatively important steps which led to the production of four major metabolites (each >5% of the sample radioactivity). RWJ-26240 was extensively metabolized in the dog, and fecal excretion was the major route of elimination of RWJ-26240 and its metabolites.
Footnotes
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Send reprint requests to: Dr. W. N. Wu, Department of Drug Metabolism, The R.W. Johnson Pharmaceutical Research Institute, McKean and Welsh Roads, Spring House, PA 19477.
- Received April 11, 1997.
- Accepted October 22, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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