Metabolism of a novel antiarrhythmic agent, bidisomide, in man: use of high resolution mass spectrometry to distinguish desisopropyl bidisomide from desacetyl bidisomide.
1. Metabolism of bidisomide, a novel antiarrhythmic agent, was studied in man, and was not extensive as evidenced by the fact that approximately 60 and 70% of the radioactive doses were recovered as the parent drug after i.v. and oral administration respectively. 2. The mass spectra of bidisomide metabolites indicate that the two major metabolic pathways of bidisomide were hydroxylation of the piperidine ring and N-dealkylation. The latter occurred on the side chain containing the piperidine ring or the isopropyl group. The N-dealkylated metabolite on the side chain containing the piperidine ring was cyclized to result in a pyrrolidone metabolite. 3. The N-dealkylated metabolite, desisopropyl bidisomide, was identified by comparing its high resolution mass spectrum to that of authentic desacetyl bidisomide. 4. In the hydroxylation pathway, both mono- and dihydroxylated metabolites of the piperidine ring were observed. The exact location of the hydroxyl groups on the piperidine ring was not determined.
Cook
C S
CS
G.D. Searle & Co., Skokie, IL 60077, USA.
Ames
G B
GB
Hribar
J D
JD
Liu
N W
NW
Sweeney
D L
DL
Schoenhard
G L
GL
Karim
A
A
D000284:Administration, Oral; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D007275:Injections, Intravenous; D013058:Mass Spectrometry; D010880:Piperidines / Q000008:administration & dosage / Q000378:metabolism*
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; C061991:bidisomide