Palego Lionella, Biondi Luciano, Giannaccini Gino, Sarno Nannina, Elmi Simona, Ciapparelli Antonio, Cassano Giovanni Battista, Lucacchini Antonio, Martini Claudia, Dell'Osso Liliana
Department of Psychiatry, University of Pisa, Italy.
Prog Neuropsychopharmacol Biol Psychiatry. 2002 Apr;26(3):473-80. doi: 10.1016/s0278-5846(01)00291-3.
Steady-state plasma concentrations of clozapine and norclozapine, its major metabolite, as well as their sum and ratio (norclozapine/clozapine), were evaluated in 50 in- and outpatients taking clozapine and naturalistically recruited. Drug plasma concentrations were measured by means of a reversed-phase high-performance liquid chromatography (RPLC) method with an ultraviolet detection. Daily doses (milligrams per kilogram of body weight) of clozapine correlated positively with clozapine plasma parameters, except with the norclozapine/clozapine ratio, in all patients. When the patients were divided in subgroups with respect to gender, the corresponding plasma concentrations were no longer dose-related in men. A lack of significant correlation was observed also in patients (n=23) co-treated with typical neuroleptics. Conversely, dose-concentration correlations were significant in either smoker or nonsmoker patients. No significant relationship between body weight and clozapine plasma parameters was reported. Further, we observed (1) a trend towards higher medians of clozapine or total analytes in women than those reported in men (P=.09 and .07); (2) no significant difference in plasma levels obtained in subjects younger than 34 years and subjects 34 years old or older; (3) a trend towards higher norclozapine and clozapine plus norclozapine levels (P=.05 and .08) in nonsmoker than smoker patients; (4) no significant difference between clozapine plasma parameters measured in patients co-medicated with typical neuroleptics and in patients receiving clozapine alone.
在50名服用氯氮平且为自然招募的门诊和住院患者中，评估了氯氮平及其主要代谢产物去甲氯氮平的稳态血浆浓度，以及它们的总和与比率（去甲氯氮平/氯氮平）。采用反相高效液相色谱（RPLC）法并结合紫外检测来测定药物血浆浓度。在所有患者中，氯氮平的每日剂量（毫克/千克体重）与氯氮平血浆参数呈正相关，但与去甲氯氮平/氯氮平比率无关。当根据性别将患者分为亚组时，男性患者相应的血浆浓度不再与剂量相关。在同时接受典型抗精神病药物治疗的患者（n = 23）中也观察到缺乏显著相关性。相反，在吸烟或不吸烟的患者中，剂量 - 浓度相关性均显著。未报告体重与氯氮平血浆参数之间存在显著关系。此外，我们观察到：（1）女性氯氮平或总分析物的中位数有高于男性的趋势（P = 0.09和0.07）；（2）年龄小于34岁的受试者与34岁及以上受试者的血浆水平无显著差异；（3）不吸烟患者的去甲氯氮平以及氯氮平加去甲氯氮平水平有高于吸烟患者的趋势（P = 0.05和0.08）；（4）同时服用典型抗精神病药物的患者与单独接受氯氮平治疗的患者所测得的氯氮平血浆参数无显著差异。
