Calarge Chadi Albert, Miller Del D
Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
J Child Adolesc Psychopharmacol. 2011 Apr;21(2):163-9. doi: 10.1089/cap.2010.0038. Epub 2011 Apr 12.
Little is known about risperidone metabolism in a clinical sample, where polypharmacy is common. Such knowledge is important since several of its side effects are dose dependent.
Medically healthy patients aged 7 to 17 years old treated with risperidone for at least 6 months were enrolled. Trough serum risperidone and 9-hydroxyrisperidone concentrations were measured.
One hundred seven participants (92% males) were recruited, representing a heterogenous clinical group with attention-deficit/hyperactivity disorder, disruptive behavior disorders, pervasive developmental disorders, anxiety disorders, mood disorders, tic disorders, or psychotic disorders. Risperidone had been used at a mean dose of 0.03 mg/kg, for a mean 2.5 years, predominantly to treat irritability and aggression. Cytochrome CYP2D6 inhibitors were divided into prominent (fluoxetine, bupropion, and lamotrigine), intermediate (sertraline), and weak inhibition groups (citalopram or escitalopram). The concentrations of risperidone and its metabolite were strongly associated with the dose of risperidone and time since the last dose and, to a lesser extent, with male sex. In addition, risperidone concentration increased with pubertal stage (p < 0.05), while body mass index z-score (p = 0.001) predicted a higher 9-hydroxyrisperidone concentration. The use of CYP2D6 inhibitors was much more strongly associated with risperidone concentration (p < 0.0001) than with its metabolite's (p = 0.06).
In chronically treated youths, the metabolism of risperidone depends on the stage of sexual development, whereas that of 9-hydroxyrisperidone varies with body fat. Moreover, CYP2D6 inhibitors more strongly affect risperidone metabolism than that of its metabolite. The clinical implications of these findings, in relation to efficacy and tolerability, deserve further investigation.
在多种药物联合使用很常见的临床样本中，关于利培酮代谢的了解甚少。由于其几种副作用与剂量相关，所以此类知识很重要。
纳入7至17岁接受利培酮治疗至少6个月的身体健康的患者。测量血清利培酮谷浓度和9-羟基利培酮浓度。
招募了107名参与者（92%为男性），代表了一个患有注意力缺陷/多动障碍、破坏性行为障碍、广泛性发育障碍、焦虑症、情绪障碍、抽动障碍或精神障碍的异质性临床群体。利培酮的平均使用剂量为0.03mg/kg，平均使用时间为2.5年，主要用于治疗易怒和攻击行为。细胞色素CYP2D6抑制剂分为强效（氟西汀、安非他酮和拉莫三嗪）、中效（舍曲林）和弱效抑制组（西酞普兰或艾司西酞普兰）。利培酮及其代谢物的浓度与利培酮剂量和末次给药后的时间密切相关，在较小程度上与男性性别有关。此外，利培酮浓度随青春期阶段升高（p<0.05），而体重指数z评分（p=0.001）预测9-羟基利培酮浓度较高。CYP2D6抑制剂的使用与利培酮浓度的相关性（p<0.0001）远高于与其代谢物浓度的相关性（p=0.06）。
在长期治疗的青少年中，利培酮的代谢取决于性发育阶段，而9-羟基利培酮的代谢则随体脂而变化。此外，CYP2D6抑制剂对利培酮代谢的影响比对其代谢物的影响更大。这些发现与疗效和耐受性相关的临床意义值得进一步研究。
