Perry P J, Bever K A, Arndt S, Combs M D
Department of Psychiatry, College of Medicine, University of Iowa, Iowa City 52242, USA.
Biol Psychiatry. 1998 Oct 15;44(8):733-8. doi: 10.1016/s0006-3223(97)00531-3.
Previous work has suggested factors such as gender, smoking behavior, dose, and age affect the amount of drug a patient requires to achieve a desired plasma concentration of clozapine. Plasma clozapine concentrations ranging from 350 to 504 ng/mL in treatment-refractory schizophrenics and schizoaffective patients produce response rates ranging approximately 55-80%. Without the aid of clozapine plasma concentration monitoring, 3-6 months are recommended for a therapeutic clozapine trial. Data suggest that the lag time to response can be reduced by administering a dose that produces a therapeutic clozapine concentration.
To generate a clozapine dosing nomogram to predict clozapine steady-state plasma concentrations, a cohort of 71 patients was collected via retrospective chart review and/or patient interview. Clozapine steady-state plasma concentrations and demographic variables were obtained. Multiple-linear regression was utilized to examine the relationship between the plasma clozapine concentration and the independent variables.
The dosing model that optimally predicted steady-state clozapine plasma concentrations included the variables dose (mg/day), smoking (yes = 0 and no = 1), gender, and a dose-gender interaction variable. The model explained 47% of the variance in the clozapine concentrations (F = 14.42, p < .001, r2 = .47). Two equations, one for male subjects, i.e., clozapine (ng/mL) = 111 (smoke) + 0.464 (dose) + 145, and one for female subjects, i.e., clozapine (ng/mL) = 111 (smoke) + 1.590 (dose)-149, were derived to predict clozapine steady-state plasma concentrations to serve as a clozapine dosing guide for clinicians.
A clozapine dosing nomogram was constructed as a clinical aid to facilitate clozapine dosing.
先前的研究表明，性别、吸烟行为、剂量和年龄等因素会影响患者达到氯氮平所需血浆浓度所需的药物量。难治性精神分裂症患者和分裂情感性障碍患者的血浆氯氮平浓度在350至504 ng/mL之间时，有效率约为55%-80%。在没有氯氮平血浆浓度监测的情况下，建议进行3-6个月的氯氮平治疗试验。数据表明，通过给予能产生治疗性氯氮平浓度的剂量，可以缩短起效延迟时间。
为了生成预测氯氮平稳态血浆浓度的剂量列线图，通过回顾性病历审查和/或患者访谈收集了71例患者。获取了氯氮平稳态血浆浓度和人口统计学变量。采用多元线性回归分析血浆氯氮平浓度与自变量之间的关系。
最佳预测氯氮平稳态血浆浓度的给药模型包括剂量（mg/天）、吸烟（是=0，否=1）、性别以及剂量-性别交互变量。该模型解释了氯氮平浓度47%的方差（F = 14.42，p <.001，r2 =.47）。得出了两个方程，一个用于男性受试者，即氯氮平（ng/mL）= 111（吸烟）+ 0.464（剂量）+ 145，另一个用于女性受试者，即氯氮平（ng/mL）= 111（吸烟）+ 1.590（剂量）-149，以预测氯氮平稳态血浆浓度，为临床医生提供氯氮平给药指导。
构建了氯氮平给药列线图作为临床辅助工具，以促进氯氮平给药。
