Winter Helen R, Earley Willie R, Hamer-Maansson Jennifer E, Davis Patty C, Smith Mark A
Clinical Pharmacokinetics, Clinical Pharmacology, Astra-Zeneca Pharmaceuticals LP, 1800 Concord Pike, Wilmington, DE 19850, USA.
J Child Adolesc Psychopharmacol. 2008 Feb;18(1):81-98. doi: 10.1089/cap.2007.0084.
The aim of this study was to investigate the steady-state pharmacokinetic, safety, and tolerability profiles of immediate-release quetiapine administered by similar dose-escalation regimens in pediatric and adult populations with psychotic or mood disorders.
Pediatric patients aged 10-17 years were titrated to a quetiapine dose of 200 mg twice daily (b.i.d. on days 5-7, 400 mg b.i.d. on days 11-12, with a final 400-mg dose on day 13. In a separate trial, adult patients aged 18-45 years were titrated to a quetiapine dose of 200 mg b.i.d. on days 4-6, 400 mg b.i.d. on days 10-11, with a final 400-mg dose on day 12. Concentrations of quetiapine and three metabolites (quetiapine sulfoxide, 7-hydroxy quetiapine, and norquetiapine) were quantified in plasma and urine. Adverse events, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests were evaluated throughout the studies.
In both pediatric and adult populations, plasma concentrations of quetiapine and norquetiapine increased proportionately as the dose was escalated from 200 mg b.i.d. to 400 mg b.i.d. There were no age-related differences in the dose-normalized quetiapine plasma concentration-time curve (AUC(SS)) and maximum plasma concentration (C(SS,max)). Quetiapine was rapidly absorbed after 200-mg and 400-mg doses in pediatric patients [median t(max) (time to maximum plasma concentration) 1.5 hours, both doses] and adult patients (median t(max) 1.0 hour and 1.2 hours, respectively). The mean quetiapine t(1/2) (terminal elimination half-life) was approximately 6 hours for pediatric and 5 hours for adult patients. Norquetiapine displayed a similar median t(max) and a longer t(1/2) compared with quetiapine. Quetiapine was well tolerated, with no serious adverse events and no unexpected events reported.
Pediatric and adult populations demonstrated similar pharmacokinetic, safety, and tolerability profiles for quetiapine administered by dose escalation. The predictability in quetiapine concentration profiles for children aged 10 years to adults suggests that no dosage adjustment may be required when treating patients of these ages.
本研究旨在调查在患有精神障碍或情绪障碍的儿童和成人中，通过相似的剂量递增方案给予速释喹硫平后的稳态药代动力学、安全性和耐受性情况。
10至17岁的儿科患者滴定至喹硫平剂量为每日两次，每次200毫克（第5至7天每日两次，每次200毫克；第11至12天每日两次，每次400毫克，第13天最终剂量为400毫克）。在另一项试验中，18至45岁的成年患者滴定至喹硫平剂量为第4至6天每日两次，每次200毫克；第10至11天每日两次，每次400毫克，第12天最终剂量为400毫克。对血浆和尿液中的喹硫平及三种代谢物（喹硫平亚砜、7-羟基喹硫平、去甲喹硫平）浓度进行定量分析。在整个研究过程中评估不良事件、生命体征、12导联心电图（ECG）及临床实验室检查。
在儿科和成人中，随着剂量从每日两次，每次200毫克递增至每日两次，每次400毫克，喹硫平和去甲喹硫平的血浆浓度成比例增加。在剂量标准化的喹硫平血浆浓度-时间曲线（AUC(SS)）和最大血浆浓度（C(SS,max)）方面，不存在与年龄相关的差异。在儿科患者（两种剂量下的中位t(max)（达到最大血浆浓度的时间）均为1.5小时）和成年患者（分别为1.0小时和1.2小时）中，200毫克和400毫克剂量的喹硫平吸收迅速。儿科患者的喹硫平平均t(1/2)（终末消除半衰期）约为6小时，成年患者约为5小时。与喹硫平相比，去甲喹硫平的中位t(max)相似，但t(1/2)更长。喹硫平耐受性良好，未报告严重不良事件和意外事件。
儿科和成人在通过剂量递增给予喹硫平时，表现出相似的药代动力学、安全性和耐受性情况。10岁儿童至成人的喹硫平浓度曲线具有可预测性，这表明在治疗这些年龄段的患者时可能无需调整剂量。
