title: Postmortem drug redistribution--human cases related to results in experimental animals.
abstract: Femoral blood is widely accepted as the most reliable postmortem specimen for drug analysis in forensic toxicology. There is considerable evidence that the drug concentrations in peripheral blood samples are closer to the antemortem level than the concentration in cardiac blood. In the present study drug concentrations measured in postmortem femoral and/or heart blood samples from eight cases were compared with the concentration found in serum samples from the same subject collected antemortem or perimortem. The drugs involved were amitriptyline, nortriptyline, imipramine, verapamil and chloroquine. Two additional cases with very early postmortem blood samples, as well as femoral blood samples from later autopsy, involved amphetamine and tetrahydrocannabinol. The results from the human cases were compared with results from rat experiments on similar drugs. The samples were analyzed by high performance liquid or gas chromatography. The cases with tricyclic antidepressants had a median postmortern femoral blood to antemortem serum drug concentration ratio of 3.3, the 95% reference range being from 1.1 to 6.0 (pooled data). Large variations of the ratios were seen. The extremes noted were 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. The low ratio in the former case could be due to attempted resuscitation, while the high ratio in the latter case is probably due to the extremely high apparent volume of distribution and a high blood to plasma concentration ratio for chloroquine. Accordingly, it is dubious whether the drug concentration found in femoral blood at autopsy can be accepted as being representative for the antemortem level. The results obtained from the human cases in the 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 representative for the findings in humans than experiments with a smaller animal like the rat. The postmortem concentration changes observed for tetrahydrocannabinol in man were found to be unpredictable, while in the accompanying experimental rat study there was a significant postmortem decrease in the tetrahydrocannabinol blood concentration measured in blood from the inferior 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 increase the possibility of reaching a correct conclusion, but reference values on drug concentrations in tissues are often missing.
authors.affiliation: National Institute of Forensic Toxicology, Oslo, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Hilberg
authors.forename: S
authors.initials: S
authors.lastname: Rogde
authors.forename: J
authors.initials: J
authors.lastname: Mørland
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001344:Autopsy; D001800:Blood Specimen Collection / Q000379:methods*; D003326:Coronary Circulation; D062787:Drug Overdose; D005260:Female; D005263:Femoral Artery; D005554:Forensic Medicine / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D011180:Postmortem Changes; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014948:Wounds, Gunshot / Q000097:blood