The effects of cimetidine and ranitidine on the pharmacokinetics of cifenline.

Twelve healthy subjects completed an open single dose study to evaluate the effect of co-administration of cimetidine and ranitidine on the pharmacokinetics of cifenline. Each subject received a single 160 mg dose of cifenline alone, in combination with cimetidine (300 mg four times daily), and with ranitidine (150 mg twice daily). The H2-receptor antagonists were given with breakfast 1 h prior to cifenline dosing and continuing for 48 h.

Bioavailability and kinetics of cibenzoline in patients with normal and impaired renal function.

To test the hypothesis that renal failure alters the disposition of cibenzoline in humans, an absolute bioavailability and elimination kinetic study was performed. We used the simultaneous administration of a stable isotope variant (SASIV). Eight healthy volunteers and eight matched hemodialysis patients each received simultaneously an 80-mg intravenous infusion of 15N-2-cibenzoline and a single 80-mg cibenzoline capsule.

Cifenline in the short-term treatment of patients with ventricular premature complexes: a double-blind placebo-controlled study.

To study the efficacy and safety of cifenline (cibenzoline), a new antiarrhythmic agent, we enrolled 46 patients with greater than 700 premature ventricular complexes (VPCs)/24 h in an ambulatory electrocardiography study. During an open-label titration phase, 25 patients showed greater than 75% VPC suppression while receiving 130 mg (15 patients) or 160 mg (10 patients) cifenline twice daily. During a double-blind placebo-controlled phase in 23 of these patients, cifenline was more effective than placebo in controlling VPCs (p less than 0.

The natural history of benign and potentially malignant ventricular arrhythmias with special reference to nonsustained ventricular tachycardia.

Ambulatory ECG recordings are routinely used to identify patients at increased risk of sudden cardiac death and to monitor changes in ventricular arrhythmias during antiarrhythmic drug therapy. The arrhythmia frequency established during the initial baseline has previously been reported to change during a second placebo monitoring period in patients with non-life-threatening ventricular arrhythmias, but the extent to which this applies to patients with nonsustained ventricular tachycardia has not been examined. To extend these observations to patients with potentially lethal ventricular arrhythmias, we studied 53 patients enrolled in one of two investigational antiarrhythmic drug trials that introduced a second single-blind placebo period (placebo-pulse) an average of 16 months after successful arrhythmia suppression.

Effect of renal impairment on the pharmacokinetics of cibenzoline.

Sixteen subjects completed an open-label study designed to assess the effect of renal impairment on the disposition of cibenzoline. The study included 10 patients with mild or moderate renal impairment creatinine clearance less than 60 ml/min/70 kg) and six healthy subjects in the same age range, each of whom received a single 130 mg oral dose of cibenzoline. The pharmacokinetic parameters observed in the healthy volunteers were similar to those reported previously.

Evaluation of dosing interval and optimum dose of cibenzoline.

Fifteen patients with ventricular premature complexes (VPCs) were included in this open study designed to assess the relative efficacy of bid (two times daily) and tid (three times daily) dosing regimens for cibenzoline as compared with qid (four times daily) administration. Patients started therapy with qid administration; this was followed in sequence by tid and bid administration at the maximum effective total daily dose determined during the qid administration. Of the nine patients evaluated for efficacy for suppression of VPCs, eight demonstrated a 75% or greater suppression of VPCs with cibenzoline administered qid (total daily dose of 130-325 mg).

Pharmacokinetics of cibenzoline after single and repetitive dosing in healthy volunteers.

Twenty-five healthy, adult male volunteers entered two open-label parallel studies, each designed to define the pharmacokinetics of single and multiple oral doses of cibenzoline. Each volunteer received a single 160-mg oral dose of cibenzoline followed two or three days later by 160 mg of cibenzoline q12h for seven days. Plasma concentration-time profiles and urinary excretion rate data were used to determine pharmacokinetic parameters for unchanged drug.

Pharmacokinetics and pharmacodynamics of intravenous cibenzoline in normal volunteers.

The pharmacokinetics of intravenous (IV) cibenzoline were studied in six healthy male volunteers ranging in age from 51 to 78 years. The subjects received intravenous (IV) cibenzoline 100 mg over 20 minutes, and plasma and urine specimens were collected for 48 hours. Cibenzoline plasma concentrations at the end of the infusion ranged from 730 to 1,420 ng/mL and exhibited triexponential decline thereafter.

Antiarrhythmic effects of cibenzoline.

Thirty-three patients with ventricular tachyarrhythmias were referred for evaluation of their arrhythmias using programmed electrical stimulation to guide antiarrhythmic therapy. Cibenzoline succinate, a new antiarrhythmic agent, was compared to procainamide in patients with ventricular tachycardia. Cibenzoline was given intravenously, initially 1.

Pharmacokinetics of oral cibenzoline in arrhythmia patients.

The pharmacokinetics of oral cibenzoline were studied in 30 arrhythmia patients as part of an ascending multiple-dose efficacy study. The elimination half-life of the drug following repetitive dosing ranged from 7.6 to 22.

The efficacy of cibenzoline in preventing PES induction of ventricular tachycardia in the dog.

The electrophysiologic effects of cibenzoline were studied using programmed electrical stimulation (PES) techniques and were compared to those of quinidine. Cibenzoline, like the conventional class 1 agent quinidine, was effective in preventing arrhythmia induction. Twelve dogs were given 0.

Single-dose pharmacokinetics and dose proportionality of oral cibenzoline.

The pharmacokinetics of cibenzoline were evaluated in four young healthy volunteers who received ascending oral doses of 65, 97.5, 130, 162.5, 195, 227.

Cibenzoline plasma concentration and antiarrhythmic effect.

The relationship between plasma concentrations of cibenzoline and its antiarrhythmic effect was evaluated in patients receiving the drug orally as part of an ascending multiple dose efficacy and tolerance study. Twenty-five patients participated in a 3-day placebo period, 3 days of 32.5 mg cibenzoline every 6 hr, 3 days of 65 mg cibenzoline every 6 hr, 3 days of 81.