Postmortem drug redistribution - Human cases related to results in experimental animals

Femoral blood is widely accepted as the most reliable postmortem specimen f or drug analysis in forensic toxicology. There is considerable evidence tha t the drug concentrations in peripheral blood samples are closer to the ant emortem level than the concentration in cardiac blood. In the present study drug concentrations measured in postmortem femoral and/or heart blood samp les from eight cases were compared with the concentration found in serum sa mples from the same subject collected antemortem or perimortem. The drugs i nvolved were amitriptyline, nortriptyline, imipramine. verapamil and chloro quine. Two additional cases with very early postmortem blood samples, as we ll as femoral blood samples from later autopsy, involved amphetamine and te trahydrocannabinol. The results from the human cases were compared with res ults from rat experiments on similar drugs. The samples were analyzed by hi gh performance liquid or gas chromatography. The cases with tricyclic antid epressants had a median postmortem femoral blood to antemortem serum drug c oncentration ratio of 3.3. the 95% reference range being from 1.1 to 6.0 (p ooled data). Large variations of the ratios were seen. The extremes noted w ere a postmortem femoral blood to antemortem serum drug concentration ratio of 0.9 in a case with nortriptyline and 49 in the case with chloroquine. T he low ratio in the former case could be due to attempted resuscitation, wh ile the high ratio in the: latter case is probably due to the extremely hig h apparent volume of distribution and a high blood to plasma concentration ratio for chloroquine. Accordingly, it is dubious whether the drug concentr ation found in femoral blood at autopsy can be accepted as bring representa tive for the antemortem level. The results obtained from the human cases in thc:present study were generally in reasonable agreement with previous rat experiments. confirming that the animal studies when interpreted carefully , are indicative of the changes observed in man as well as a previous study in pigs. Studies on drug concentrations in pigs are not necessarily more r epresentative for the findings in humans than experiments with a smaller an imal like the rat. The postmortem concentration changes observed for tetrah ydrocannabinol in man were found to be unpredictable, while in the accompan ying experimental rat study there was a significant postmortem decrease in the tetrahydrocannabinol blood concentration measured in blood from the inf erior vena cava. In special cases where the diagnosis of overdose is to be used as judicial evidence, a single sample of blood may prove insufficient. In such cases, analyses of several samples of blood and tissue will increa se the possibility of reaching a correct conclusion, but reference values o n drug concentrations in tissues are often missing.