Till J A, Shinebourne E A, Rowland E, Ward D E, Bhamra R, Haga P, Johnston A, Holt D W
Department of Paediatric Cardiology, Brompton Hospital, London.
Br Heart J. 1989 Aug;62(2):133-9. doi: 10.1136/hrt.62.2.133.
Twenty three children with recurrent supraventricular tachycardia were treated with flecainide. Twenty one of these received intravenous treatment during an attack (2 mg/kg over 10 minutes). The tachycardia was terminated in 17. After an intravenous bolus of flecainide, blood samples were drawn at regular intervals for analysis of flecainide concentration over 48 hours. Pharmacokinetic variables were calculated--median terminal half life 7.5 hours, median volume of distribution 6.2 l/kg, and median plasma clearance 7.2 ml/min/kg. There was a significant correlation between half life and age. Twenty of the children received long term treatment with an oral preparation of flecainide to prevent further attacks. Twelve had no further attacks and 16 were considered to have good control. Two children suffered potentially serious arrhythmogenic effects soon after the start of oral treatment and flecainide had to be stopped. During oral treatment regular blood samples were drawn and plasma concentrations were analysed to assess the therapeutic range. This did not differ substantially from that proposed in adults (400-800 micrograms/l). Eight children were electively withdrawn from oral flecainide to see whether they really needed it. Blood samples for measurement of flecainide concentration were drawn after their last oral dose. Pharmacokinetic variables were calculated: time to maximum concentration 2 hours, median terminal half life 7.9 hours. For the combined data from patients receiving intravenous and oral treatment there was a significant correlation between elimination half life and age. An intravenous dose of 2 mg/kg over at least 10 minutes and an initial oral dose of 6 mg/kg/day in three divided doses is recommended. Treatment should be started in hospital so that children in whom the drug may be arrhythmogenic can be identified and plasma concentrations measured to identify patients in whom lack of efficacy is caused by underdosage.
23名患有复发性室上性心动过速的儿童接受了氟卡尼治疗。其中21名在发作期间接受了静脉治疗(10分钟内给予2mg/kg)。17名儿童的心动过速得以终止。静脉推注氟卡尼后,定期采集血样以分析48小时内的氟卡尼浓度。计算了药代动力学变量——中位终末半衰期7.5小时,中位分布容积6.2l/kg,中位血浆清除率7.2ml/min/kg。半衰期与年龄之间存在显著相关性。20名儿童接受了氟卡尼口服制剂的长期治疗以预防进一步发作。12名儿童未再发作,16名被认为控制良好。2名儿童在开始口服治疗后不久出现了潜在的严重致心律失常作用,不得不停用氟卡尼。在口服治疗期间,定期采集血样并分析血浆浓度以评估治疗范围。这与成人建议的范围(400 - 800微克/升)没有实质性差异。8名儿童被选择性地停用口服氟卡尼以观察他们是否真的需要它。在他们最后一次口服剂量后采集血样以测量氟卡尼浓度。计算了药代动力学变量:达峰时间2小时,中位终末半衰期7.9小时。对于接受静脉和口服治疗患者的综合数据,消除半衰期与年龄之间存在显著相关性。建议至少10分钟内静脉给予2mg/kg剂量,初始口服剂量为6mg/kg/天,分三次服用。治疗应在医院开始,以便识别可能对药物产生心律失常作用的儿童,并测量血浆浓度以识别因剂量不足导致疗效不佳的患者。