Chang W H, Lin S K, Lane H Y, Hu W H, Jann M W, Lin H N
Laboratory of Biological Psychiatry, Taipei City Psychiatric Center, Taiwan ROC.
J Formos Med Assoc. 1997 Aug;96(8):599-605.
Steady-state plasma concentrations of clozapine and its metabolites, desmethylclozapine and clozapine-N-oxide, were measured in 162 Taiwanese patients with refractory schizophrenia. The daily doses of clozapine ranged from 100 to 900 mg, with a mean value of 379.5 +/- 142.2 mg. A dosage of 400 mg/day or lower was used for most patients (n = 131, 81%). Plasma concentrations of clozapine and its two major metabolites were measured using high performance liquid chromatography with ultraviolet detection. The mean plasma clozapine concentration was 566.9 +/- 398.8 ng/mL. The plasma concentrations of desmethylclozapine and clozapine-N-oxide were 46% and 16% of the concentration of the parent drug, respectively. We used an approximate rule that each 100 mg/day dose results in about 150 ng/mL plasma clozapine. This value is about 30% to 50% higher than that reported in Caucasians. The suggested therapeutic plasma clozapine concentration range of 300 to 700 ng/mL can be achieved with a dose range of 200 to 500 mg/day in most Taiwanese patients. Dose-dependent plasma clozapine concentrations were found. The interpatient variation was up to 12-fold in patients receiving the same dose, eg, 400 mg/day (n = 62). In four of these patients, the plasma drug concentrations were very high (1,446 +/- 114 ng/mL). The application of therapeutic drug monitoring in clozapine-treated patients with refractory schizophrenia is important, not only in dose adjustment, prediction of severe side effects such as seizures, and exploration of drug interactions, but also in the effective use of this expensive drug.
在162名台湾难治性精神分裂症患者中测量了氯氮平及其代谢产物去甲氯氮平和氯氮平 - N - 氧化物的稳态血浆浓度。氯氮平的日剂量范围为100至900毫克，平均值为379.5±142.2毫克。大多数患者（n = 131，81%）使用的剂量为400毫克/天或更低。采用高效液相色谱 - 紫外检测法测量氯氮平及其两种主要代谢产物的血浆浓度。氯氮平的平均血浆浓度为566.9±398.8纳克/毫升。去甲氯氮平和氯氮平 - N - 氧化物的血浆浓度分别为母体药物浓度的46%和16%。我们采用了一个近似规则，即每100毫克/天的剂量会使血浆氯氮平浓度增加约150纳克/毫升。这个值比白种人中报道的值高约30%至50%。对于大多数台湾患者，日剂量范围为200至500毫克/天可达到建议的氯氮平治疗血浆浓度范围300至700纳克/毫升。发现了剂量依赖性的血浆氯氮平浓度。接受相同剂量（例如400毫克/天，n = 62）的患者之间的个体差异高达12倍。在其中4名患者中，血浆药物浓度非常高（1446±114纳克/毫升）。在氯氮平治疗的难治性精神分裂症患者中应用治疗药物监测很重要，这不仅有助于剂量调整、预测严重副作用（如癫痫发作）和探索药物相互作用，还能有效使用这种昂贵的药物。
