AGE-DEPENDENCE OF FLECAINIDE PHARMACOKINETICS

Aim: The aim of the study was to evaluate the relationship between age and the pharmacokinetics of flecainide. Methods: Fifteen patients with frequent premature ventricular contractions and with normal renal function were selected and divided into two groups: elderly (greater than or equal to 60 years) and younger patients (< 60 years). Flecainide pharmacokinetics were studied either after acute oral administration (200 mg) of the drug or at the end of a 21-day course (150 mg twice daily). Results: In elderly patients, the plasma half-life of flecainide after chronic treatment was significantly longer than that after acute oral administration (22.1 +/- 4.3 compared with 12.1 +/- 2.3 h, P< 0.001; mean half-life 84% longer after chronic administration). In the younger patients, the half-lives of flecainide after acute and chronic treatment were not significantly different (11.2 +/- 2.9 compared with 13.9 +/- 3.2h). In both groups, the area under the concentration-time curve (AUC) after drug administration increased during chronic treatment (P<0.001 in both cases), although the change was proportionally greater in the elderly group (an increase of 139% compared with 76% in the other group). After both acute and chronic treatment with flecainide, the AUC was higher in the elderly than in the younger patients (P< 0.05 for acute and P< 0.005 for chronic treatment, respectively). The half-life of flecainide during chronic treatment and the observed percentage increases in AUC during chronic treatment were significantly related to the age of the patient (r = 0.73, P< 0.005 and r= 0.66, P<0.01, respectively). Conclusion: Flecainide kinetics are strictly dependent on the age of the patient; in elderly people, even in those with normal renal function, the drug exhibits non-linear kinetics. In clinical practice, when treating patients over the age of 60 years with flecainide, the initial dosage should be reduced and monitoring of the plasma concentration of the drug should be considered.