Bachmann Christian J, Haberhausen Michael, Heinzel-Gutenbrunner Monika, Remschmidt Helmut, Theisen Frank M
Department of Child and Adolescent Psychiatry, University Hospital Marburg and Giessen, Campus Marburg, Germany.
Ther Drug Monit. 2008 Feb;30(1):108-12. doi: 10.1097/FTD.0b013e3181633429.
Olanzapine (OLZ) is a widely used antipsychotic substance. Therapeutic drug monitoring (TDM) of OLZ is recommended but is based on known reference ranges derived from intraindividual and interindividual variability measurements. There have been few studies on the interindividual variability of OLZ serum concentrations in adolescents, and no data on intraindividual variability are available. This study explored the intraindividual variability of OLZ serum concentrations in 85 patients attending a child and adolescent psychiatric hospital (age at first assessment: mean +/- SD, 16.7 +/- 2.0; range, 10.3-20.6 years; 54 male, 31 female). A total of 577 steady-state OLZ serum concentrations (2 to 24 measurements per patient; mean, 6.8, and SD, +/-5.4) were measured, using high-performance liquid chromatography (HPLC). Intraindividual variability of dose-corrected OLZ serum concentrations was 1.04- to 10.7-fold. The intraindividual variabilities of the metabolites OLZ N-desmethyl (DMO) and OLZ 2-hydroxymethyl (2OH) were 1.08- to 83.2-fold and 1.0- to 47-fold, respectively. Intraindividual variability of OLZ (DMO; 2OH) serum concentration accounted for 47% (89.8%, 74.9%) of total variance. OLZ daily dose, number of co-medications, body mass index (BMI), age, and post-dose interval had a significant influence on the intraindividual variability of dose-corrected OLZ serum concentrations (all P < 0.001). The serum concentrations of OLZ and OLZ metabolites in adolescents show high intraindividual variability, potentially limiting the value of TDM. It is recommended that repeated serum concentration measurements are made in individuals treated with OLZ, in order to obtain a more precise estimate of the intraindividual variability of serum concentrations.
奥氮平（OLZ）是一种广泛使用的抗精神病药物。推荐对奥氮平进行治疗药物监测（TDM），但该监测基于从个体内和个体间变异性测量得出的已知参考范围。关于青少年奥氮平血清浓度个体间变异性的研究较少，且尚无个体内变异性的数据。本研究探讨了85名在儿童和青少年精神病医院就诊患者（首次评估年龄：均值±标准差，16.7±2.0岁；范围，10.3 - 20.6岁；54名男性，31名女性）奥氮平血清浓度的个体内变异性。使用高效液相色谱法（HPLC）共测量了577个稳态奥氮平血清浓度（每位患者测量2至24次；均值为6.8，标准差为±5.4）。剂量校正后的奥氮平血清浓度个体内变异性为1.04至10.7倍。代谢物奥氮平N - 去甲基（DMO）和奥氮平2 - 羟甲基（2OH）的个体内变异性分别为1.08至83.2倍和1.0至47倍。奥氮平（DMO；2OH）血清浓度的个体内变异性分别占总变异的47%（89.8%，74.9%）。奥氮平每日剂量、合并用药数量、体重指数（BMI）、年龄和给药后间隔时间对剂量校正后的奥氮平血清浓度个体内变异性有显著影响（所有P < 0.001）。青少年奥氮平和奥氮平代谢物的血清浓度显示出较高的个体内变异性，这可能会限制TDM的价值。建议对接受奥氮平治疗的个体进行多次血清浓度测量，以便更精确地估计血清浓度的个体内变异性。
