Plasma and tissue levels of flecainide in rats

The time-courses of flecainide plasma and tissue levels were studied in Wistar male rats after i.v. administration (4 mg/Kg). Drug assay in plasma and tissue was performed with a specific and accurate HPLC technique. The final half lives in plasma and tissues were about 4 hours, except in the brain where the half life value was 9.8 hours. The mean tissue/plasma (T/P) ratios in myocardial, kidney, liver, skeletal and muscle tissues were 9.11, 13.8, 14.37, 6.31 respectively, while in the brain the T/P ratio rose progressively over the sampling time to 10.0. These data suggest that flecainide may accumulate in the central nervous system during prolonged treatment. Flecainide levels in adipose tissue were very low. Finally, there was an early "bulge" in the concentration curve, possibly reflecting enterohepatic circulation or non-linear elimination kinetics.