1991 Volume 22 Issue 4 Pages 767-772
In this study, flecainide acetate (FLC) was orally administered by single dosage to twenty-five patients ventricular premature contractions and the FLC doses were 100 (n=5), 200 (n=13) and 300mg (n=7), respectively. The pharmacokinetics of FLC was analyzed by one compartment open model with lag time. The area under the plasma concentration-time curve (AUC) and the systemic clearance (Clsys) were calculated by means of the trapezoidal method. Good linear relationships between the maximum plasma concentration (Cmax; mg/l) and dose (mg/kg), and between the AUC (mg·hr/l) and dose (mg) were seen (P<0.01). Moreover, the change in dose had no influence on the elimination half-life (t1/2), the apparent volume of distribution, the Clsys, the lag time and the time of the Cmax (12.8hr, 382l, 21.5l/hr, 0.69hr and 3.29hr, respectively). However, the t1/2 values of three patients were longer than 25hr and the serum creatinine values in the patients were higher than 1.4mg/dl (normal range 0.7-1.4mg/dl). The kinetics of renal excretion of FLC was studied in the patients whose urine is able to be collected (n=8). The percentage of FLC excreted during 0-24hr or 0-48hr showed no significant difference between 200 and 300mg doses and the mean values were 19.8% for 0-24hr and 28.4% for 0-48hr. The renal and non-renal clearances were 6.28 and 13.93l/hr, respectively. However, the biggest renal clearance value was approximately 5.5 times bigger than the smallest ones. The FLC plasma concentrations at steady state after multiple dosing (200mg/12hr) were simulated using pharmacokinetic parameters obtained from the patients with the biggest, the mean and the smallest t1/2 (1.729, 0.649 and 0.406mg/l, respectively). These results suggest that therapeutic drug monitoring of FLC is necessary since the average plasma concentration at steady state may be exceed toxic level in patients with hepatic or renal dysfunction.
