Effect of congestive heart failure on the pharmacokinetics of cibenzoline.
Six patients with chronic congestive heart failure (CHF) (New York Heart Association functional class II or III) and five healthy subjects completed this study designed to determine if CHF alters the pharmacokinetics and absolute bioavailability of cibenzoline when compared with healthy subjects. Each subject or patient was administered a one-hour intravenous infusion of 80 mg of 15N2-cibenzoline and simultaneously received an 80-mg oral dose of cibenzoline that allowed for analytic separation of each route of administration. Resulting plasma concentration-time profiles and urinary excretion rate data were used to determine pharmacokinetic parameters for cibenzoline. There were no statistically significant differences in any pharmacokinetic parameter between patients with CHF and healthy subjects. The absolute bioavailability ranged from 74% to 97% in those with CHF. The volume of distribution following the intravenous dose ranged from 3.4 to 6.1 L/kg, and plasma clearance ranged from 245 to 642 mL/min, with an apparent elimination half-life of approximately ten hours. Approximately 60% of the dose was recovered in the urine. Overall, the pharmacokinetics of cibenzoline in patients with chronic CHF do not differ from those observed in healthy subjects.
Massarella
J W
JW
Department of Drug Metabolism, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
Silvestri
T
T
DeGrazia
F
F
Miwa
B
B
Keefe
D
D
D000368:Aged; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged
D007093:Imidazoles; C032151:cifenline