Clinical Drug Investigation

, Volume 17, Issue 1, pp 51–58 | Cite as

A Bioequivalence Study of Brand and Generic Clozapine in Patients with Schizophrenia

Pharmacokinetic and Tolerability Findings
  • John J. Sramek
  • Ravi Anand
  • Richard D. Hartman
  • Horst F. Schran
  • Jameel Hourani
  • Sharon Barto
  • Tom S. Wardle
  • Thomas M. Shiovitz
  • Neal R. Cutler
Clinical Pharmacokinetics


Objective: This inpatient, randomised, three-way crossover study evaluated the steady-state pharmacokinetics and tolerability of generic clozapine (Creighton) versus Clozaril® (Novartis brand of clozapine) in patients with schizophrenia.

Setting: Patients were hospitalised throughout the study.

Patients: Thirty patients meeting DSM-III-R criteria for a diagnosis of schizophrenia participated in this study.

Design: Clozaril® was titrated over 5 days from 12.5 to 75mg twice daily, after which patients received all of the following 1-week regimens in random order: Clozaril® — one 100mg tablet twice daily; clozapine — four 25mg tablets twice daily; and clozapine — one 100mg tablet twice daily.

Main Outcome Measures and Results: Both the 25 and 100mg dose forms of clozapine were bioequivalent to Clozaril® 100mg, justifying their interchange-ability; mean area under the concentration-time curve (AUC0–12) values were 2683 ± 1613, 2781 ± 1775, and 2547 ± 1429 μg/L·h, respectively. The most common adverse events were dizziness and asthenia. Tolerability findings between groups were comparable, although a high incidence (20%) of symptomatic orthostatic hypotension during the initial titration of Clozaril® emphasised the need for careful monitoring, even in the target patient population.

Conclusions: The results of this study demonstrated that the 25 and 100mg dose forms of generic clozapine and Clozaril® 100mg are bioequivalent, which should ensure comparable efficacy and tolerability with the clinical use of either product.


Schizophrenia Adis International Limited Clozapine Schizophrenic Patient Bioequivalence Study 
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Copyright information

© Adis International Limited 1999

Authors and Affiliations

  • John J. Sramek
    • 1
  • Ravi Anand
    • 2
  • Richard D. Hartman
    • 2
  • Horst F. Schran
    • 2
  • Jameel Hourani
    • 1
  • Sharon Barto
    • 1
  • Tom S. Wardle
    • 1
  • Thomas M. Shiovitz
    • 1
  • Neal R. Cutler
    • 1
  1. 1.California Clinical TrialsBeverly HillsUSA
  2. 2.Novartis Pharmaceuticals CorporationEast HanoverUSA

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