The disposition and metabolic fate of 14C-cibenzoline in man.
The disposition and metabolic fate of cibenzoline (CBZ) following single oral 153-mg doses of 14C-CBZ succinate were studied in five healthy adult males. The mean maximum plasma radioactivity of 386 ng eq/ml occurred at 2.4 hr after administration. The mean half-life, determined from the 14C plasma concentration and urinary excretion rate data, was 13.1 and 14.8 hr, respectively. The mean maximum CBZ concentration was 196 ng/ml at 1.2 hr post-dose. The mean half-life, determined from the plasma concentration and urinary excretion rate data, was 7.2 and 7.3 hr, respectively. The mean total clearance of radioactivity and CBZ was 300 ml/min and 1224 ml/min, respectively, due to elimination via both renal and nonrenal pathways. The only unconjugated metabolite in the plasma was 4,5-dehydrocibenzoline which, together with other unidentified metabolites, is presumed responsible for the longer observed half-life for total radioactivity. Approximately 75% of the dose was recovered in the urine in the first 24 hr after dosing, 80% of which was present at CBZ and known metabolites. After 6 days, a mean of 85.7% of the dose was excreted in urine and 13.2% in feces. The predominant excreted compound was CBZ (55.7% of the dose) in the 0-72 hr urine. Although several metabolites were identified in urine samples, none were found in substantial amounts relative to the parent drug. Two of these substances showed slight antiarrhythmic activity, whereas the 4,5-dehydro metabolite, representing approximately 4% of radioactivity in urine, was inactive.
Massarella
J W
JW
Loh
A C
AC
Williams
T H
TH
Szuna
A J
AJ
Sandor
D
D
Bressler
R
R
Leinweber
F J
FJ
D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000378:metabolism*; D001711:Biotransformation; D002250:Carbon Radioisotopes; D006207:Half-Life; D006801:Humans; D007093:Imidazoles / Q000378:metabolism*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008657:Metabolic Clearance Rate
D000889:Anti-Arrhythmia Agents; D002250:Carbon Radioisotopes; D007093:Imidazoles; C032151:cifenline