Disposition and metabolic fate of 14C-cibenzoline in man

Journal Article · Wed Jan 01 04:00:00 EST 1986 · Drug Metab. Dispos.; (United States)

OSTI ID:5681202

Massarella, J W; Loh, A C; Williams, T H; Szuna, A J; Sandor, D; Bressler, R; Leinweber, F J

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.

• Research Organization: Hoffmann-La Roche Inc., Nutley, NJ
• OSTI ID: 5681202
• Journal Information: Drug Metab. Dispos.; (United States), Journal Name: Drug Metab. Dispos.; (United States) Vol. 1; ISSN DMDSA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
AZOLES
BIOCHEMICAL REACTION KINETICS
CARBON 14 COMPOUNDS
CLEARANCE
DISTRIBUTION
DRUGS
EXCRETION
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAGNETIC RESONANCE
MALES
MAMMALS
MAN
MEN
METABOLISM
METABOLITES
NUCLEAR MAGNETIC RESONANCE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PRIMATES
REACTION KINETICS
RESONANCE
RETENTION
TISSUE DISTRIBUTION
TRACER TECHNIQUES
VERTEBRATES