Psychiatry Investig.  2015 Jul;12(3):356-360. 10.4306/pi.2015.12.3.356.

Bioequivalence of Generic and Brand Name Clozapine in Korean Schizophrenic Patients: A Randomized, Two-Period, Crossover Study

• Woo YS
• Wang HR
• Yoon BH
• Lee SY
• Lee KH
• Seo JS
• Bahk WM

• KMID: 2316496
• DOI: http://doi.org/10.4306/pi.2015.12.3.356

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 C(max,ss) values for Clzapine and Clozaril were 524.62 and 551.18 ng/mL, and the mean AUC(0-12) values were 4479.90 hr.ng/mL and 4724.56 hr.ng/mL, respectively. The 90% CI values for the natural logarithmically transformed C(max,ss) and AUC(0-12) 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.
CONCLUSION
Generic clozapine (Clzapine) appears to be bioequivalent to brand name clozapine (Clozaril).

Keyword

Clozapine; Schizophrenia; Bioequivalence; Generic

MeSH Terms

Clozapine*
Cross-Over Studies*
Electrocardiography
Humans
Pharmacokinetics
Physical Examination
Plasma
Prospective Studies
Schizophrenia
Therapeutic Equivalency*
Vital Signs
Clozapine