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Pharmacopsychiatry 2004; 37(2): 63-68
DOI: 10.1055/s-2004-815527
Original Paper
© Georg Thieme Verlag Stuttgart · New York

Olanzapine Plasma Concentration, Average Daily Dose, and Interaction with Co-Medication in Schizophrenic Patients

N. Bergemann1 , A. Frick1 , P. Parzer2 , J. Kopitz3
  • 1Department of Psychiatry, University of Heidelberg
  • 2Department of Child- and Adolescent Psychiatry, University of Heidelberg
  • 3Institute of Pathochemistry and General Neurochemistry, University of Heidelberg
Further Information

Publication History

Received: 12.10.2000 Revised: 21.2.2001

Accepted: 24.1.2003

Publication Date:
29 March 2004 (online)

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Background: Olanzapine, a thienobenzodiazepine, is one of the relatively new atypical antipsychotic drugs. The lowest threshold of effective olanzapine plasma levels in inpatient treatment is assumed to be 9 ng/ml [28]. Very little is known about the plasma concentration in patients at various oral doses of olanzapine or about the clinically relevant interactions with co-medications. Methods: In 71 schizophrenic patients (age 32.6 ± 12.1, range 18-63 years; 31 women, 40 men), plasma olanzapine levels were assessed in 377 tests by high-performance liquid chromatography (HPLC) with electrochemical detection. Fifty-six of these plasma levels were assessed while patients were receiving olanzapine as monotherapy; otherwise, the plasma levels were assessed with the patients receiving various co-medications. Results: The mean daily oral dose of olanzapine was 17.5 mg (SD = 7.0, range 5-40 mg), and the mean olanzapine plasma concentration was 54.2 ng/ml (SD 37.8 ng/ml, range 1.2-208 ng/ml). The plasma concentration of olanzapine increased linearly with the daily oral dose (r = 0.64, p < 0.001). A multiple variance analysis considering age and sex as covariables showed a significant difference in the dose-corrected plasma levels of olanzapine among 40 smokers and 31 non-smokers; age and sex did not affect the dose-corrected plasma levels. However, women received a significantly lower daily dose of olanzapine under routine clinical study conditions. No differences could be detected among the dose-corrected plasma concentration of those patients who were taken off olanzapine because they did not respond (n = 14) or because of side effects (n = 5) and those who were discharged while still on olanzapine. Under the co-medication with fluvoxamine, significantly higher dose-corrected olanzapine plasma concentrations were found than with olanzapine monotherapy, whereas significantly lower dose-corrected olanzapine plasma concentrations were detected under lithium and trimipramine co-medication. Under co-medication with amitriptyline, benperidol, carbamazepine, flupentixol, and lorazepam, the dose-corrected olanzapine plasma concentrations were no different than the plasma levels under olanzapine monotherapy. Conclusions: The relevance of therapeutic drug monitoring is emphasized with respect to the data presented and to the literature. Future studies should examine, in particular, the effects of a wider range of co-medications in a larger patient sample.

References

Dr. med. Dipl.-Psych. Niels Bergemann

Department of Psychiatry, University of Heidelberg

Voss-Str. 4

D-69118 Heidelberg

Germany

Phone: +49(0)6221/56-5411, -4466

Fax: +49(0)6221/56-5477

Email: niels_bergemann@med.uni-heidelberg.de