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Effect of congestive heart failure on the pharmacokinetics of cibenzoline
J W Massarella1, T Silvestri, F DeGrazia
1Department of Drug Metabolism, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
Insights
Chronic congestive heart failure (CHF) does not alter the pharmacokinetics or bioavailability of cibenzoline. This study found no significant differences in drug processing between CHF patients and healthy individuals.
Area of Science:
- Pharmacology
- Clinical Pharmacology
- Cardiology
Background:
- Chronic congestive heart failure (CHF) can alter drug pharmacokinetics.
- Cibenzoline is an antiarrhythmic drug.
- Understanding cibenzoline's behavior in CHF is crucial for patient management.
Purpose of the Study:
- To investigate the pharmacokinetic profile and absolute bioavailability of cibenzoline in patients with chronic CHF.
- To compare cibenzoline pharmacokinetics between CHF patients and healthy subjects.
Main Methods:
- A comparative pharmacokinetic study involving six CHF patients (NYHA class II-III) and five healthy subjects.
- Administration of intravenous and oral doses of 15N2-cibenzoline.
- Analysis of plasma concentration-time profiles and urinary excretion data.
Main Results:
- No statistically significant differences in pharmacokinetic parameters were observed between CHF patients and healthy subjects.
- Absolute bioavailability of cibenzoline in CHF patients ranged from 74% to 97%.
- Key pharmacokinetic parameters (volume of distribution, clearance, half-life) were consistent across both groups.
Conclusions:
- Chronic congestive heart failure does not significantly alter the pharmacokinetics or absolute bioavailability of cibenzoline.
- Cibenzoline can be safely administered to CHF patients without dose adjustment based on altered pharmacokinetics.
Abstract:
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.