|SOFT - TIAFT 1998||Poster Session 3||Thursday October 8, 1998|
OLANZAPINE CONCENTRATIONS IN CLINICAL SERUM AND FORENSIC BLOOD SPECIMENS - WHEN DOES THERAPEUTIC BECOME TOXIC?|
Michael D. Robertson
National Medical Services Inc., 3701 Welsh Road Willow Grove, PA 19090, U.S.A.
|Olanzapine (Zyprexa®) is a new drug for the treatment of schizophrenia that has been reported to provide favorable anti-psychotic efficacy with minimal adverse side effects. Very little has been reported in the literature with respect to plasma concentrations following clinical dosing. A therapeutic range of 9 to 23 ng/mL has been proposed. Similarly very little has been reported about olanzapine concentrations contributing to, or causing death. In one reported case of suicide involving olanzapine, the olanzapine concentration in whole blood was 4100 ng/mL. The objective of this paper is to present the concentrations of olanzapine in 1655 clinical samples together with concentrations of olanzapine detected in post-mortem whole blood specimens received by NMS.
The analysis of olanzapine was performed by the solid phase extraction of 1.0 ml of buffered serum or blood, followed by GC separation with nitrogen-phosphorus detection.
The analysis of 1655 patient samples showed that 70 % of positive serum values were below 40 ng/mL, with a mean and median of 36 and 26 ng/mL, respectively, and only 10% were above 70 ng/mL. The mean olanzapine concentration in 22 forensic whole blood specimens was 318 ng/mL with a range of 6 ng/mL to 1600 ng/mL. Case studies in which olanzapine toxicity is believed to have contributed to death will also be presented.
From these results it appears that the therapeutic range may be higher than those previously reported. The results also suggest that due to the absence of any extensive literature relating olanzapine concentrations and toxicity, potential toxicity at concentrations above 80 ng/mL should be considered.