Olanzapine plasma concentration, average daily dose, and interaction with co-medication in schizophrenic patients

Pharmacopsychiatry. 2004 Mar;37(2):63-8. doi: 10.1055/s-2004-815527.


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. 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.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Antipsychotic Agents / blood*
  • Antipsychotic Agents / therapeutic use
  • Benzodiazepines / blood*
  • Benzodiazepines / therapeutic use
  • Biometry
  • Chi-Square Distribution
  • Chromatography, High Pressure Liquid / methods
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Drug Monitoring / methods*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Olanzapine
  • Schizophrenia / blood*
  • Schizophrenia / drug therapy
  • Sex Factors
  • Smoking / blood
  • Spectrophotometry, Ultraviolet / methods


  • Antipsychotic Agents
  • Benzodiazepines
  • Olanzapine