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Multiple-Dose Pharmacokinetics of Clozapine in Patients

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Abstract

After a 2-day buildup, patients were dosed continuously with clozapine solution at three ascending dose levels (37.5, 75, and 150 mg bid for 7 days at each dose level). Following the morning administration on the twenty-third day of dosing a drug holiday was instituted which lasted for a minimum of 48 hr. Serial plasma samples were obtained during each of the periods and during the drug holiday for the calculation of the steady-state parameters AUCSS, CSS max, and CSS min at each dose level as well as for the assessment of the terminal elimination rate. Mean parameter values for AUGSS, CSS max, and CSS min showed a linearly increasing response with the dose, well described by a straight line passing through the origin. The terminal elimination appeared to follow linear kinetics and had a mean half-life of 15.8 hr (range, 5.8–33 hr).

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Author information

Authors and Affiliations

  1. Sandoz Research Institute, East Hanover, New Jersey, 07936

    Miles G. Choc

  2. Department of Statistics, School of Business Administration, Temple University, Philadelphia, Pennsylvania, 19122

    Frances Hsuan

  3. Veterans Administration Medical Center, Augusta, Georgia, 30910

    Richard Borison

  4. New York University and Nathan S. Kline Institute for Psychiatric Research, Manhattan Psychiatric Center, Ward's Island, New York, New York, 10035

    Jan Volavka

Authors
  1. Miles G. Choc
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  2. Robert G. Lehr
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  3. Frances Hsuan
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  4. Gilbert Honigfeld
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  5. Harold T. Smith
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  6. Richard Borison
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  7. Jan Volavka
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Choc, M.G., Lehr, R.G., Hsuan, F. et al. Multiple-Dose Pharmacokinetics of Clozapine in Patients. Pharm Res 4, 402–405 (1987). https://doi.org/10.1023/A:1016434312388

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  • DOI: https://doi.org/10.1023/A:1016434312388

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