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The disposition of the new antiarrhythmic agent cibenzoline (CBZ) (racemic 4,5-dihydro-2-(2,2-diphenylcyclopropyl)-1H-imidazole) in three male dogs was investigated after oral administration of 13.8 mg/kg of 14C-CBZ base. Within 6 days, 60.5 +/- 6.0% of the dose was excreted in urine and 19.2 +/- 4.6% in feces. In 0-24-hr urine, unchanged drug was excreted (41.6% of the dose) as well as the unconjugated 4,5-dehydro metabolite (DHCBZ, 3.7%), conjugated p-hydroxybenzophenone (0.8%, only in one dog), and a phenolic metabolite, p-hydroxycibenzoline (HCBZ) in a rearranged form (RHCBZ) at 5.2% of the dose (free plus conjugated). Studies with synthetic HCBZ indicated that unrearranged HCBZ was excreted and that rearrangement occurred during purification. CBZ from dog urine displayed slight optical activity, based on ORD/CD data, corresponding to an optical purity of 15% of the S-(-)-CBZ, indicating a limited extent of stereoselective metabolism of CBZ in dogs. After an oral 50-mg/kg dose of 14C-CBZ succinate, male rats excreted in 3 days 27.0 +/- 2.8% in urine and 41.5 +/- 2.6% of the dose in feces, and in a repeated experiment 32.1 +/- 1.9% in urine and 54.5 +/- 0.7% in feces. CBZ (7.6%) and DHCBZ (0.2%) were determined in 0-24-hr urine, and CBZ (4.2%) and RHCBZ (4.2% of the dose) were determined in 0-24-hr feces. RHCBZ (3.1%), m-methoxy p-hydroxycibenzoline (8.3%), and p-hydroxybenzophenone (5.3% of the dose) were identified as glucuronide/sulfate conjugates in bile from rats. Evidence that p-hydroxybenzophenone arose from an unstable unidentified metabolite is discussed.
A C Loh, and
T H Williams, and
J W Tilley, and
G J Sasso, and
A J Szuna, and
J J Carbone, and
V Toome, and
F J Leinweber
June 1966,
The Journal of biological chemistry,
A C Loh, and
T H Williams, and
J W Tilley, and
G J Sasso, and
A J Szuna, and
J J Carbone, and
V Toome, and
F J Leinweber
March 2017,
Regulatory toxicology and pharmacology : RTP,
A C Loh, and
T H Williams, and
J W Tilley, and
G J Sasso, and
A J Szuna, and
J J Carbone, and
V Toome, and
F J Leinweber
January 2018,
Journal of toxicology and environmental health. Part A,
A C Loh, and
T H Williams, and
J W Tilley, and
G J Sasso, and
A J Szuna, and
J J Carbone, and
V Toome, and
F J Leinweber
June 2006,
Drug metabolism and disposition: the biological fate of chemicals,
A C Loh, and
T H Williams, and
J W Tilley, and
G J Sasso, and
A J Szuna, and
J J Carbone, and
V Toome, and
F J Leinweber
August 2009,
Drug metabolism and disposition: the biological fate of chemicals,
A C Loh, and
T H Williams, and
J W Tilley, and
G J Sasso, and
A J Szuna, and
J J Carbone, and
V Toome, and
F J Leinweber
May 1986,
Antimicrobial agents and chemotherapy,
A C Loh, and
T H Williams, and
J W Tilley, and
G J Sasso, and
A J Szuna, and
J J Carbone, and
V Toome, and
F J Leinweber
January 1986,
Xenobiotica; the fate of foreign compounds in biological systems,
A C Loh, and
T H Williams, and
J W Tilley, and
G J Sasso, and
A J Szuna, and
J J Carbone, and
V Toome, and
F J Leinweber
May 2023,
Xenobiotica; the fate of foreign compounds in biological systems,
A C Loh, and
T H Williams, and
J W Tilley, and
G J Sasso, and
A J Szuna, and
J J Carbone, and
V Toome, and
F J Leinweber
January 1988,
Pharmacology,
A C Loh, and
T H Williams, and
J W Tilley, and
G J Sasso, and
A J Szuna, and
J J Carbone, and
V Toome, and
F J Leinweber
May 1987,
Xenobiotica; the fate of foreign compounds in biological systems,
