title: Bioequivalence of Generic and Brand Name Clozapine in Korean Schizophrenic Patients: A Randomized, Two-Period, Crossover Study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Generic clozapine (Clzapine) appears to be bioequivalent to brand name clozapine (Clozaril).
authors.affiliation: Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Young Sup
authors.initials: YS
authors.lastname: Woo
authors.affiliation: Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Hee-Ryung
authors.initials: HR
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Naju National Hospital, Naju, Republic of Korea.
authors.forename: Bo-Hyun
authors.initials: BH
authors.lastname: Yoon
authors.affiliation: Department of Psychiatry, School of Medicine, Wonkwang University, Iksan, Republic of Korea.
authors.forename: Sang-Yeol
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, College of Medicine, Dongguk University, Gyeongju, Republic of Korea.
authors.forename: Kwang Hun
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, School of Medicine, Konkuk University, Chungju, Republic of Korea.
authors.forename: Jeong Seok
authors.initials: JS
authors.lastname: Seo
authors.affiliation: Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Won-Myong
authors.initials: WM
authors.lastname: Bahk
keywords: Bioequivalence; Clozapine; Generic; Schizophrenia