The extent of postmortem drug redistribution in a rat model

The aim of this study was to investigate the postmortem redistribution of s everal drugs in a rat model and to examine if any of the pharmacological pr operties was related to the extent of this phenomenon. One of the following drugs: phenobarbital (phenobarbitone), acetaminophen (paracetamol), carbam azepine, codeine, verapamil, amphetamine, mianserin, trimeprazine (alimemaz ine) or chloroquine was administered together with nortriptyline orally to rats 90 min prior to sacrifice. Heart blood was sampled immediately before sacrifice and after 2 h postmortem, as it has previously been shown that th is is sufficient time for postmortem concentration changes to occur in hear t blood. Blood was also sampled from the clamped abdominal inferior vena ca va (representing peripheral blood) and tissue samples were taken from lungs , myocardium, liver, kidney, thigh muscle, forebrain, and vitreous humor to gether with a specimen from the minced carcass. Drugs were analyzed by high performance Liquid or gas chromatography. For phenobarbital, acetaminophen and carbamazepine the postmortem to antemortem blood drug concentration ra tios were close to 1.0 and tissue concentrations were low. The postmortem t o antemortem heart blood drug concentration ratio for chloroquine (6.9 +/- 1.5) was higher than for nortriptyline (3.5 +/- 0.3), and the remaining dru gs (codeine, verapamil, amphetamine, mianserin, and trimeprazine) showed ra tios of the same magnitude as nortriptyline. The postmortem to antemortem b lood drug concentration ratios for both heart blood and blood from the vena cava and also the lung to antemortem blood drug concentration ratio were c losely related to the apparent volume of distribution for the drugs studied (p < 0.001). Accordingly, an apparent volume of distribution of more than 3-4 L/kg is a good predictor that a drug is liable to undergo postmortem re distribution with significant increments in blood levels. The postmortem dr ug concentration in blood from vena cava was closely related to the antemor tem blood level, confirming that among the postmortem samples, the peripher al blood sample was the most representative for the antemortem blood concen tration.