ChloroquineV1, Main, Exploration, bibRecord, 002588

The extent of postmortem drug redistribution in a rat model.

Identifieur interne : 002588 ( Main/Exploration ); précédent : 002587; suivant : 002589

The extent of postmortem drug redistribution in a rat model.

Auteurs : T. Hilberg [Norvège] ; A. Ripel ; L. Sl Rdal ; A. Bj Rneboe ; J. M Rland

Source :

Journal of forensic sciences [ 0022-1198 ] ; 1999.

RBID : pubmed:10486948

Descripteurs français

KwdFr :
- Animaux, Modifications postmortem, Mâle, Médecine légale (), Pharmacocinétique, Préparations pharmaceutiques (métabolisme), Rat Wistar, Rats, Répartition dans les tissus.
MESH :
- métabolisme : Préparations pharmaceutiques.
- Animaux, Modifications postmortem, Mâle, Médecine légale, Pharmacocinétique, Rat Wistar, Rats, Répartition dans les tissus.

English descriptors

KwdEn :
- Animals, Forensic Medicine (methods), Male, Pharmaceutical Preparations (metabolism), Pharmacokinetics, Postmortem Changes, Rats, Rats, Wistar, Tissue Distribution.
MESH :
- chemical , metabolism : Pharmaceutical Preparations.
- methods : Forensic Medicine.
- Animals, Male, Pharmacokinetics, Postmortem Changes, Rats, Rats, Wistar, Tissue Distribution.

Abstract

The aim of this study was to investigate the postmortem redistribution of several drugs in a rat model and to examine if any of the pharmacological properties was related to the extent of this phenomenon. One of the following drugs: phenobarbital (phenobarbitone), acetaminophen (paracetamol), carbamazepine, codeine, verapamil, amphetamine, mianserin, trimeprazine (alimemazine) 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 this is sufficient time for postmortem concentration changes to occur in heart blood. Blood was also sampled from the clamped abdominal inferior vena cava (representing peripheral blood) and tissue samples were taken from lungs, myocardium, liver, kidney, thigh muscle, forebrain, and vitreous humor together 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 ratios were close to 1.0 and tissue concentrations were low. The postmortem to antemortem heart blood drug concentration ratio for chloroquine (6.9 +/- 1.5) was higher than for nortriptyline (3.5 +/- 0.3), and the remaining drugs (codeine, verapamil, amphetamine, mianserin, and trimeprazine) showed ratios of the same magnitude as nortriptyline. The postmortem to antemortem blood drug concentration ratios for both heart blood and blood from the vena cava and also the lung to antemortem blood drug concentration ratio were closely 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 redistribution with significant increments in blood levels. The postmortem drug concentration in blood from vena cava was closely related to the antemortem blood level, confirming that among the postmortem samples, the peripheral blood sample was the most representative for the antemortem blood concentration.

PubMed: 10486948

Affiliations:

Le document en format XML

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<front><div type="abstract" xml:lang="en">The aim of this study was to investigate the postmortem redistribution of several drugs in a rat model and to examine if any of the pharmacological properties was related to the extent of this phenomenon. One of the following drugs: phenobarbital (phenobarbitone), acetaminophen (paracetamol), carbamazepine, codeine, verapamil, amphetamine, mianserin, trimeprazine (alimemazine) 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 this is sufficient time for postmortem concentration changes to occur in heart blood. Blood was also sampled from the clamped abdominal inferior vena cava (representing peripheral blood) and tissue samples were taken from lungs, myocardium, liver, kidney, thigh muscle, forebrain, and vitreous humor together 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 ratios were close to 1.0 and tissue concentrations were low. The postmortem to antemortem heart blood drug concentration ratio for chloroquine (6.9 +/- 1.5) was higher than for nortriptyline (3.5 +/- 0.3), and the remaining drugs (codeine, verapamil, amphetamine, mianserin, and trimeprazine) showed ratios of the same magnitude as nortriptyline. The postmortem to antemortem blood drug concentration ratios for both heart blood and blood from the vena cava and also the lung to antemortem blood drug concentration ratio were closely 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 redistribution with significant increments in blood levels. The postmortem drug concentration in blood from vena cava was closely related to the antemortem blood level, confirming that among the postmortem samples, the peripheral blood sample was the most representative for the antemortem blood concentration.</div>
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The extent of postmortem drug redistribution in a rat model.

The extent of postmortem drug redistribution in a rat model.

Source :

Descripteurs français

English descriptors

Abstract

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