Distribution of Fluoxetine and Norfluoxetine in Postmortem Fluids and Tissues

摘要

During aviation accident investigations, postmortem specimens from the flight crews are submitted to the Federal Aviation Administration's Civil Aerospace Medical Institute for toxicological analysis. Fluoxetine (Prozac) is a selective serotonin reuptake inhibitor that was introduced in 1986. Certain side effects of this medication - drowsiness, dizziness, abnormal vision, diarrhea, and headache - could affect pilot performance and become a factor in an aviation accident. Our laboratory has determined the distribution of fluoxetine and its desmethyl metabolite, norfluoxetine, in various postmortem tissues and fluids from 10 fatal aviation accident cases. When available, 11 specimen types were analyzed for each case, including: blood, urine, vitreous humor, bile, liver, kidney, skeletal muscle, lung, spleen, heart muscle, and brain. Specimens were extracted using solid-phase extraction and analyzed by GC/MS. Deuterated fluoxetine and norfluoxetine were used as internal standards to eliminate any possible matrix effects during extraction. Blood fluoxetine concentrations in these 10 cases ranged from 21 to 1480 ng/mL. Most cases fell within the expected therapeutic range for patients that regularly take this drug. The distribution coefficients for fluoxetine were determined to be: urine 0.9 +/- 0.4, vitreous humor 0.10 +/- 0.03, bile 9 +/- 1, liver 38 +/- 10, lung 60 +/- 17, kidney 9 +/- 3, spleen 20 +/- 5, muscle 2.2 +/- 0.3, brain 15 +/- 3, and heart 10 +/- 2. While the coefficient of variation (CV) for the distribution coefficients range from 11-44%, the distribution into heart, brain, muscle, spleen, and bile is relatively reproducible, each having a CV of less or equal 25%. To our knowledge, this is the first report presenting the distribution of fluoxetine in humans at therapeutic concentrations.