Postmortem changes in blood tranylcypromine concentration: competing redistribution and degradation effects.
Site and temporal changes in tranylcypromine (TCP) and lithium concentrations in blood were studied in a human poisoning case. Blood samples from peripheral vessels and six central vessels were obtained at 0, 6, 24, 48 and 72 h after starting the autopsy. Nine tissue samples were obtained on completion. TCP showed preferential concentration in liver (2.21 micrograms/g) and brainstem (2.46 micrograms/g). There was a moderate post mortem redistribution phenomenon with TCP concentrations lowest in peripheral blood (0.17 micrograms/ml) at 0 h and highest in central vessels at 24 h (0.52 micrograms/ml). At 72 h blood TCP concentrations fell below those at 0 time but the samples showed marked putrefactive changes. Control blood samples spiked with TCP and incubated for 48 h at 37 degrees C showed a 58% fall in drug concentration. By contrast with TCP, lithium, which has a small Vd (0.8 l/kg) and is chemically stable, did not show this pattern of change in blood concentration. The site and temporal differences in TCP concentration in blood can be explained by the competing effects of post mortem redistribution and drug degradation. Redistribution is an early post mortem phenomenon characterised by diffusion, along a concentration gradient, from drug reservoirs in solid organs into adjacent blood vessels. Drug degradation is a later phenomenon associated with putrefactive change.
Yonemitsu
K
K
Department of Forensic Medicine, Kumamoto University, Japan.
Pounder
D J
DJ
D062787:Drug Overdose / Q000097:blood / Q000378:metabolism / Q000473:pathology; D005554:Forensic Medicine; D006801:Humans; D008094:Lithium / Q000032:analysis / Q000097:blood* / Q000493:pharmacokinetics / Q000506:poisoning*; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D011180:Postmortem Changes; D013997:Time Factors; D014018:Tissue Distribution; D014191:Tranylcypromine / Q000032:analysis / Q000097:blood* / Q000493:pharmacokinetics / Q000506:poisoning*
D014191:Tranylcypromine; D008094:Lithium