Metabolism of actisomide in the dog, monkey and man: a novel rearrangement of N-dealkylated metabolites.
The metabolism of actisomide, a novel antiarrhythmic agent, was studied in the dog, monkey and man and was found to be more extensive in the monkey than in the dog or man. The major metabolites identified were a piperidinyl hydroxylated metabolite, the mono-N-dealkylated, cyclized and piperidine hydroxylated metabolite, and the cyclized and mono-N-dealkylated metabolite. Excretion of the parent drug was higher in urine than in feces in the dog, but in the monkey and man, urinary and fecal excretion of actisomide was similar. In all species the metabolites were primarily excreted in feces.
Cook
C S
CS
Department of Drug Metabolism, Searle Research and Development, Skokie, Illinois 60077.
Rozek
L F
LF
Hribar
J
J
Schoenhard
G L
GL
Karim
A
A
D000328:Adult; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003640:Dealkylation; D004285:Dogs; D005243:Feces / Q000737:chemistry; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D011744:Pyrimidinones / Q000378:metabolism*; D013045:Species Specificity
D000889:Anti-Arrhythmia Agents; D002250:Carbon Radioisotopes; D011744:Pyrimidinones; C051827:SC 36602