RT Journal Article
SR Electronic
T1 Dose-dependent tissue uptake of flecainide during chronic administration in rabbits.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 228
OP 231
VO 16
IS 2
A1 R Kannan
A1 A Matin-Asgari
YR 1988
UL http://dmd.aspetjournals.org/content/16/2/228.abstract
AB This study was designed to examine the metabolism of flecainide after repeated administration to rabbits. New Zealand White rabbits were administered either 7.5 mg/kg body weight (dose I) or 20 mg/kg body weight (dose II) flecainide twice daily intraperitoneally for 12-14 days. Serum, heart, liver, lung, kidney, muscle, fat, and brain were collected upon death. Flecainide concentrations in serum and tissues were determined by a liquid chromatographic procedure standardized in our laboratory. Serum and tissue flecainide concentrations showed a significant, dose-dependent increase after chronic administration. Flecainide accumulated in lung, liver, kidney, and heart, its concentration decreasing in that order. Tissue to serum flecainide ratios also followed a similar pattern. Cornea and urine contained flecainide metabolites which were not characterized. Only traces of flecainide were detected in brain and fat tissues. Substantial tissue uptake of flecainide should be considered in long term flecainide therapy.