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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Disposition kinetics and dynamics of nicainoprol, a new antiarrhythmic agent, in humans.

Kinetics and resting and exercise-induced hemodynamic and ECG effects of nicainoprol, a new antiarrhythmic structurally resembling propafenone or propranolol, were investigated in eight healthy male subjects receiving a 1-hour infusion (100 mg) and oral dose (200 mg) in a randomized-crossover fashion. Nicainoprol in plasma and urine was determined by a specific HPLC assay. Plasma concentration-time data were fitted to a triexponential equation. Mean postinfusion kinetic data were: alpha-phase half-life = 3.1 minutes, beta-phase half-life = 106.6 minutes, and gamma-phase half-life = 12.4 hours; volume of central compartment = 0.114 L/kg; steady-state volume of distribution = 0.67 L/kg; total clearance = 3.6 ml/min/kg; and renal clearance = 0.56 ml/min/kg. Absolute bioavailability was approximately 70% and peak plasma drug concentration occurred 2.3 hours after oral administration. Interindividual variability in AUC was 1.6- and 2.4-fold after intravenous and oral administration, respectively. Cumulative fraction excreted unchanged in urine was approximately 15% and 9% of the dose after intravenous and oral administration, respectively. Resting heart rates were increased, whereas exercise-induced heart rates were unchanged after both doses. QRS durations were widened after both doses. PR and QTc intervals were prolonged during intravenous study. The results suggest that nicainoprol is an enzyme-limited or poorly extracted drug suitable for both intravenous and oral administration and devoid of beta-blocking action in humans, at least with doses tested in this study. Its ECG properties appear to be similar to those of class I antiarrhythmics.[1]

References

  1. Disposition kinetics and dynamics of nicainoprol, a new antiarrhythmic agent, in humans. Ishizaki, T., Horai, Y., Kubota, K., Minegishi, A., Echizen, H., Chiba, K. Clin. Pharmacol. Ther. (1987) [Pubmed]
 
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