Grothe D R, Calis K A, Jacobsen L, Kumra S, DeVane C L, Rapoport J L, Bergstrom R F, Kurtz D L
Clinical Center Pharmacy Department, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1196, USA.
J Clin Psychopharmacol. 2000 Apr;20(2):220-5. doi: 10.1097/00004714-200004000-00015.
Well-designed studies investigating how pediatric or adolescent patients with mental disorders respond to and metabolize the newer antipsychotic drugs are practically nonexistent. Without such data, clinicians have difficulty designing appropriate dosage regimens for patients in these age groups. The results from a study of olanzapine pharmacokinetics in children and adolescents are described. Eight inpatients (ages 10-18 years) with treatment-resistant childhood-onset schizophrenia received olanzapine (2.5-20 mg/day) over 8 weeks. Blood samples, collected during dose titration and at a steady state provided pharmacokinetic data. The final evaluation (week 8) included extensive sampling for 36 hours after a 20-mg dose. Olanzapine concentrations in these eight pediatric patients were of the same magnitude as those for nonsmoking adult patients with schizophrenia but may be as much as twice the typical olanzapine concentrations in patients with schizophrenia who smoke. Olanzapine pharmacokinetic evaluation gave an apparent mean oral clearance of 9.6 +/- 2.4 L/hr and a mean elimination half-life of 37.2 +/- 5.1 hours in these young patients. The determination of the initial olanzapine dose for adolescent patients should take into consideration factors such as the patient's size. In general, however, the usual dose recommendation of 5 to 10 mg once daily with a target dose of 10 mg/day is likely a good clinical guideline for most adolescent patients on the basis of our pharmacokinetics results.
实际上，几乎不存在设计良好的研究来调查患有精神障碍的儿科或青少年患者如何对新型抗精神病药物做出反应以及如何代谢这些药物。没有这些数据，临床医生很难为这些年龄组的患者设计合适的给药方案。本文描述了一项关于奥氮平在儿童和青少年中的药代动力学研究结果。八名患有难治性儿童期起病精神分裂症的住院患者（年龄10 - 18岁）在8周内接受了奥氮平治疗（2.5 - 20毫克/天）。在剂量滴定期间和稳态时采集的血样提供了药代动力学数据。最终评估（第8周）包括在服用20毫克剂量后36小时进行广泛采样。这八名儿科患者体内的奥氮平浓度与不吸烟的成年精神分裂症患者的浓度相当，但可能是吸烟的精神分裂症患者中典型奥氮平浓度的两倍之多。在这些年轻患者中，奥氮平药代动力学评估得出的表观平均口服清除率为9.6 +/- 2.4升/小时，平均消除半衰期为37.2 +/- 5.1小时。确定青少年患者的初始奥氮平剂量时应考虑患者体型等因素。然而，总体而言，基于我们的药代动力学结果，对于大多数青少年患者来说，通常推荐的每日一次5至10毫克、目标剂量为10毫克/天的剂量可能是一个不错的临床指导原则。
