Tsuboi T, Bies R R, Suzuki T, Takeuchi H, Nakajima S, Graff-Guerrero A, Mamo D C, Caravaggio F, Plitman E, Mimura M, Pollock B G, Uchida H
Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan.
Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA.
Pharmacopsychiatry. 2015 Nov;48(7):286-91. doi: 10.1055/s-0035-1565070. Epub 2015 Oct 27.
Due to high inter-individual variability in peripheral pharmacokinetic parameters, dosing of antipsychotics currently relies on clinical trial-and-error, and predicting antipsychotic plasma concentrations before changing a dose has been a challenge.
Patients with schizophrenia receiving a stable dose of olanzapine were included. 2 plasma samples were collected at 2 given time points for the measurement of plasma olanzapine concentrations. At least 7 days after a dosage change of olanzapine, a third sample was collected. The plasma concentration of the third sample was predicted in a blinded fashion using a mixed-effects model with NONMEM(®), using the following information: the 2 baseline plasma concentrations, the interval between the last dose and blood draw, and clinical and demographic information.
31 subjects (mean±SD age=56.0±11.6; 19 men) were enrolled. The mean prediction (95% confidence interval) errors were 1.6 (-2.8 to 6.0) ng/mL. A highly significant correlation was observed between the observed and predicted concentrations of the third sample (r=0.91, p<0.001).
Plasma olanzapine concentrations following an actual dosage change can be predicted in advance with a high degree of certainty.
由于外周药代动力学参数存在高度个体间变异性，目前抗精神病药物的给药依赖于临床试验和试错法，并且在改变剂量之前预测抗精神病药物的血浆浓度一直是一项挑战。
纳入接受稳定剂量奥氮平治疗的精神分裂症患者。在两个给定时间点采集两份血浆样本以测量血浆奥氮平浓度。在奥氮平剂量改变至少7天后，采集第三份样本。使用NONMEM®的混合效应模型，以盲法预测第三份样本的血浆浓度，使用以下信息：两份基线血浆浓度、最后一剂与采血之间的时间间隔以及临床和人口统计学信息。
共纳入31名受试者（平均±标准差年龄=56.0±11.6；19名男性）。平均预测（95%置信区间）误差为1.6（-2.8至6.0）ng/mL。观察到第三份样本的观察浓度与预测浓度之间存在高度显著相关性（r=0.91，p<0.001）。
实际剂量改变后的血浆奥氮平浓度可以高度确定地提前预测。
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