Kannan R, Matin-Asgari A
Department of Medicine, UCLA School of Medicine.
Drug Metab Dispos. 1988 Mar-Apr;16(2):228-31.
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.
本研究旨在检测反复给家兔用药后氟卡尼的代谢情况。将新西兰白兔按7.5毫克/千克体重（剂量I）或20毫克/千克体重（剂量II）给予氟卡尼，每日两次腹腔注射，持续12 - 14天。处死动物后收集血清、心脏、肝脏、肺、肾脏、肌肉、脂肪和脑。血清和组织中的氟卡尼浓度通过我们实验室标准化的液相色谱法测定。长期给药后，血清和组织中的氟卡尼浓度呈显著的剂量依赖性增加。氟卡尼在肺、肝脏、肾脏和心脏中蓄积，其浓度按此顺序降低。组织与血清氟卡尼浓度比也呈现类似模式。角膜和尿液中含有未鉴定的氟卡尼代谢物。在脑和脂肪组织中仅检测到痕量的氟卡尼。长期氟卡尼治疗时应考虑氟卡尼在组织中的大量摄取。
