Olanzapine concentrations in clinical serum and postmortem blood specimens- When does therapeutic become toxic?

The concentration of olanzapine (Zyprexa(R)) was determined in 1653 clinica l serum specimens during routine drug monitoring, and in 58 postmortem whol e blood specimens as part of routine toxicological analysis. The analysis o f olanzapine was performed by the solid-phase extraction of 1.0 mt of buffe red serum or blood, followed by gas chromatography separation with nitrogen -phosphorus detection. The analysis of the clinical serum samples showed th at 86% of positive serum values were within the range of 5 to 75 ng/mL, wit h a mean and median of 36 and 26 ng/mL, respectively. These data suggest th at the concentrations of olanzapine expected during therapy may be higher t han those previously reported. In 58 postmortem whole blood specimens the m ean olanzapine concentration was 358 ng/mL with a range of 10 to 5200 ng/mL . Further, investigation of deaths involving olanzapine suggest that potent ial toxicity should be considered at concentrations above 100 ng/mL. Althou gh the majority of the olanzapine-related deaths were associated with many other drugs, death primarily duc to olanzapine toxicity was determined at c oncentrations in postmortem blood as low as 160 ng/mL.