Flynn Joseph T, Nahata Milap C, Mahan John D, Portman Ronald J
Division of Pediatric Nephrology, Children's Hospital at Montefiore/Albert Einstein College of Medicine, Bronx, New York, USA.
J Clin Pharmacol. 2006 Aug;46(8):905-16. doi: 10.1177/0091270006289844.
A population pharmacokinetic study was conducted in 74 hypertensive children (mean age 10.4 +/- 4.4 years [mean +/- SD]) receiving amlodipine (mean dose 0.17 +/- 0.13 mg/kg/d) chronically. Multiple blood samples were obtained from each subject to characterize amlodipine pharmacokinetics. Plasma amlodipine concentrations were determined by liquid chromatography/mass spectrophotometry with multiple-reaction monitoring detection. Population pharmacokinetic analysis was performed using NONMEM. Amlodipine concentrations were similar in subjects dosed either once or twice daily. Amlodipine pharmacokinetics were well described by a 1-compartment model with first-order absorption and elimination. For a subject at the population median weight (45 kg), predicted apparent clearances (CL/F) were 23.7 L/h for males and 17.6 L/h for females, and the apparent volume of distribution (V/F) was 25.1 L/kg. Dosing frequency did not appear to affect amlodipine concentrations in children. Weight-adjusted CL/F and V/F of amlodipine in younger children were significantly greater than in older children, suggesting a need for higher doses when treating young children with amlodipine.
对74名长期接受氨氯地平治疗（平均剂量0.17±0.13mg/kg/d）的高血压儿童（平均年龄10.4±4.4岁[平均值±标准差]）进行了群体药代动力学研究。从每个受试者采集多个血样以表征氨氯地平的药代动力学。采用液相色谱/质谱联用多反应监测检测法测定血浆氨氯地平浓度。使用NONMEM进行群体药代动力学分析。每日给药一次或两次的受试者中氨氯地平浓度相似。氨氯地平的药代动力学可用具有一级吸收和消除的单室模型很好地描述。对于群体中位体重（45kg）的受试者，预测的男性表观清除率（CL/F）为23.7L/h，女性为17.6L/h，表观分布容积（V/F）为25.1L/kg。给药频率似乎不影响儿童体内的氨氯地平浓度。年幼儿童中氨氯地平的体重校正CL/F和V/F显著高于年长儿童，提示用氨氯地平治疗年幼儿童时需要更高剂量。
