Woo Young Sup, Wang Hee-Ryung, Yoon Bo-Hyun, Lee Sang-Yeol, Lee Kwang Hun, Seo Jeong Seok, Bahk Won-Myong
Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Psychiatry, Naju National Hospital, Naju, Republic of Korea.
Psychiatry Investig. 2015 Jul;12(3):356-60. doi: 10.4306/pi.2015.12.3.356. Epub 2015 Jul 6.
Clozapine is the treatment of choice for refractory schizophrenia. The aim of this study was to compare the pharmacokinetics of the brand name (Clozaril) formulation and a generic formulation (Clzapine) of clozapine in Korean schizophrenic patients.
A prospective, randomized, crossover study was conducted to evaluate the steady-state pharmacokinetic profiles of Clozaril and Clzapine. Schizophrenic patients were randomized to receive either the brand name or generic formulation (100 mg twice daily) for 10 days, followed by the other formulation for 10 days. Plasma samples were collected on the last day of each treatment period.
Twenty-two of 28 patients (78.6%) completed the study. The mean Cmax,ss values for Clzapine and Clozaril were 524.62 and 551.18 ng/mL, and the mean AUC0-12 values were 4479.90 hr·ng/mL and 4724.56 hr·ng/mL, respectively. The 90% CI values for the natural logarithmically transformed Cmax,ss and AUC0-12 ratios (Clzapine to Clozaril) after a single oral dose (100 mg) were 0.934 (0.849-1.028) and 0.936 (0.869-1.008), respectively. Five patients (20.8%) among 24 patients who took Clzapine reported 11 adverse events and six adverse events were reported by four patients (15.4%) among 26 who took Clozaril; there were no significant differences on physical examination or in vital signs, ECG, and laboratory tests between groups.
Generic clozapine (Clzapine) appears to be bioequivalent to brand name clozapine (Clozaril).
氯氮平是难治性精神分裂症的首选治疗药物。本研究旨在比较氯氮平的品牌制剂（氯氮平片）和通用制剂（氯氮平）在韩国精神分裂症患者中的药代动力学。
进行了一项前瞻性、随机、交叉研究，以评估氯氮平片和氯氮平的稳态药代动力学特征。精神分裂症患者被随机分为接受品牌制剂或通用制剂（每日两次，每次100毫克），持续10天，随后接受另一种制剂10天。在每个治疗期的最后一天采集血浆样本。
28名患者中有22名（78.6%）完成了研究。氯氮平和氯氮平片的平均稳态峰浓度（Cmax,ss）值分别为524.62和551.18纳克/毫升，平均药时曲线下面积（AUC0-12）值分别为4479.90小时·纳克/毫升和4724.56小时·纳克/毫升。单次口服剂量（100毫克）后，氯氮平与氯氮平片的稳态峰浓度和药时曲线下面积比值（自然对数转换后）的90%置信区间值分别为0.934（0.849-1.028）和0.936（0.869-1.008）。服用氯氮平的24名患者中有5名（20.8%）报告了11起不良事件，服用氯氮平片的26名患者中有4名（15.4%）报告了6起不良事件；两组在体格检查、生命体征、心电图和实验室检查方面无显著差异。
通用型氯氮平（氯氮平）似乎与品牌型氯氮平（氯氮平片）具有生物等效性。
