McConville B J, Arvanitis L A, Thyrum P T, Yeh C, Wilkinson L A, Chaney R O, Foster K D, Sorter M T, Friedman L M, Brown K L, Heubi J E
Univeristy of Cincinnati College of Medicine, Ohio, USA.
J Clin Psychiatry. 2000 Apr;61(4):252-60. doi: 10.4088/jcp.v61n0403.
This is the first investigation of the pharmacokinetics, tolerability, and efficacy of quetiapine fumarate in adolescents with chronic or intermittent psychotic disorders.
Ten patients with DSM-IV chronic or intermittent psychotic disorders (ages 12.3 through 15.9 years) participated in an open-label, rising-dose trial and received oral doses of quetiapine twice daily (b.i.d.), starting at 25 mg b.i.d. and reaching 400 mg b.i.d. by day 20. The trial ended on day 23. Key assessments were pharmacokinetic analysis of plasma quetiapine concentrations and neurologic, safety, and efficacy evaluations.
No statistically significant differences were observed between 100-mg b.i.d. and 400-mg b.i.d. quetiapine regimens for total body clearance, dose-normalized area under the plasma concentration-time curve, or dose-normalized premorning- or postmorning-dose trough plasma values obtained under steady-state conditions after multiple-dose regimens. No unexpected side effects occurred with quetiapine therapy, and no statistically significant changes from baseline were observed for the UKU Side Effect Rating Scale items that were rated. No serious adverse events or clinically important changes in hematology or clinical chemistry variables were reported. The most common adverse events were postural tachycardia and insomnia. Extrapyramidal side effects improved, as evidenced by significant (p < .05) decreases from baseline to endpoint in the mean Simpson-Angus Scale total scores and Barnes Akathisia Scale scores. Quetiapine improved positive and negative symptoms, as shown by significant (p < .05) decreases from baseline to endpoint in the mean Brief Psychiatric Rating Scale total score, the Clinical Global Impressions-Severity of Illness scale, and the Modified Scale for the Assessment of Negative Symptoms summary score.
Quetiapine pharmacokinetics were dose proportional in adolescents and were similar to those previously reported for adults. Quetiapine was well tolerated and effective in the small number of adolescents studied.
这是对富马酸喹硫平在患有慢性或间歇性精神障碍的青少年中的药代动力学、耐受性和疗效的首次研究。
10名患有DSM-IV慢性或间歇性精神障碍的患者（年龄在12.3至15.9岁之间）参与了一项开放标签、剂量递增试验，每天两次口服喹硫平（bid），起始剂量为25mg bid，到第20天达到400mg bid。试验于第23天结束。主要评估包括血浆喹硫平浓度的药代动力学分析以及神经学、安全性和疗效评估。
在多剂量方案达到稳态条件后，对于总体清除率、血浆浓度-时间曲线下剂量标准化面积或剂量标准化早晨给药前或早晨给药后谷值血浆值，100mg bid和400mg bid喹硫平方案之间未观察到统计学上的显著差异。喹硫平治疗未出现意外副作用，对于所评估的UKU副作用评定量表项目，与基线相比未观察到统计学上的显著变化。未报告严重不良事件或血液学及临床化学变量的临床重要变化。最常见的不良事件是体位性心动过速和失眠。锥体外系副作用有所改善，平均辛普森-安格斯量表总分和巴恩斯静坐不能量表评分从基线到终点显著降低（p < 0.05）证明了这一点。喹硫平改善了阳性和阴性症状，平均简明精神病评定量表总分、临床总体印象-疾病严重程度量表以及阴性症状评估修订量表总分从基线到终点显著降低（p < 0.05）表明了这一点。
喹硫平在青少年中的药代动力学与剂量成比例，且与先前报道的成人药代动力学相似。在所研究的少数青少年中，喹硫平耐受性良好且有效。
