Olanzapine Concentrations in Clinical Serum and Postmortem Blood Specimens-When Does Therapeutic Become Toxic?

The concentration of olanzapine (Zyprexa®) was determined in 1653 clinical serum specimens during routine drug monitoring, and in 58 postmortem whole blood specimens as part of routine toxicological analysis. The analysis of olanzapine was performed by the solid-phase extraction of 1.0 mL of buffere...

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Bibliographic Details
Published in:Journal of forensic sciences 2000-03, Vol.45 (2), p.418-421
Main Authors: Robertson, MD, McMullin, MM
Format: Article
Language:English
Subjects:
Antipsychotic Agents - blood
Antipsychotic Agents - pharmacology
Antipsychotic Agents - poisoning
Autopsy
Benzodiazepines
Blood Chemical Analysis
Dose-Response Relationship, Drug
Drugs
Forensic Medicine
Forensic sciences
Humans
Pirenzepine - analogs & derivatives
Pirenzepine - blood
Pirenzepine - pharmacology
Pirenzepine - poisoning
Toxicology
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Summary:The concentration of olanzapine (Zyprexa®) was determined in 1653 clinical serum specimens during routine drug monitoring, and in 58 postmortem whole blood specimens as part of routine toxicological analysis. The analysis of olanzapine was performed by the solid-phase extraction of 1.0 mL of buffered serum or blood, followed by gas chromatography separation with nitrogen-phosphorus detection. The analysis of the clinical serum samples showed that 86% of positive serum values were within the range of 5 to 75 ng/mL, with a mean and median of 36 and 26 ng/mL, respectively. These data suggest that the concentrations of olanzapine expected during therapy may be higher than those previously reported. In 58 postmortem whole blood specimens the mean olanzapine concentration was 358 ng/mL with a range of 10 to 5200 ng/mL. Further, investigation of deaths involving olanzapine suggest that potential toxicity should be considered at concentrations above 100 ng/mL. Although the majority of the olanzapine-related deaths were associated with many other drugs, death primarily due to olanzapine toxicity was determined at concentrations in postmortem blood as low as 160 ng/mL.
ISSN:0022-1198
1556-4029
DOI:10.1520/JFS14697J