Vailleau J L, Jeanny B, Chomard P, Vincent R
CHS La Chartreuse, service Pharmacie, Dijon.
Encephale. 1996 Mar-Apr;22(2):103-9.
Measures of plasma clozapine were carried out for 15 subjects, for up to 35 months. A positive quadratic relation (r = 0.528, n = 111, p < 0.01) has been established by using different samples at different times from each patient. From 500 mg/day this relation point to forecast an important growth of clozapine plasma concentrations. The analysis of individual data shows a large variability for the individuals and a relative stability in plasma levels for a subject having one posology. The repetition of the dosages attests the compliance. A case of epilepsy, related to an important clozapine level, is presented. So, in practice, even if neither non linear pharmacokinetics, nor genetic polymorphism have been demonstrated, over a posology of 500 mg/day, it seems interesting to proceed a clozapine dosage before increasing the posology and so reduce the comitial seizure risk.
对15名受试者进行了长达35个月的血浆氯氮平测量。通过在不同时间从每位患者采集不同样本,建立了正二次关系(r = 0.528,n = 111,p < 0.01)。从500毫克/天起,这种关系表明氯氮平血浆浓度会有显著增长。个体数据分析显示个体间存在很大差异,而接受一种给药方案的受试者血浆水平相对稳定。重复给药证明了依从性。文中介绍了一例与氯氮平高血药浓度相关的癫痫病例。所以,在实际应用中,即使尚未证实存在非线性药代动力学或基因多态性,但在给药方案超过500毫克/天的情况下,在增加给药剂量前进行氯氮平剂量测定似乎很有意义,这样可以降低癫痫发作风险。