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Post-mortem redistribution of three beta-blockers in the rabbit

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Abstract

To consider the role of the physico-chemical properties of drugs in their post-mortem redistribution, we designed the present study to investigate the influence of lipophilicity using an experimental rabbit model. Three beta-blockers (BB), atenolol, metoprolol and propranolol, with a similar dissociation constant (pK a) and increasing partition coefficient (K p) were administered intravenously to 18 rabbits. One hour after the last administration, the animals were killed by thiopental injection and placed in a supine position at room temperature. Autopsies were performed at 0, 2, 6, 12, 24 and 48 h post-mortem. Concentrations of the three BB were determined in fluids (right and left cardiac blood, peripheral blood, urine, bile, stomach content, vitreous humour) and tissues (cardiac muscle, lungs, liver, brain, diaphragm, iliopsoas muscle) using a previously published, validated liquid chromatography–electrospray–mass spectrometry method. Our results show that lipophilicity influences post-mortem redistribution of the molecules in a certain number of anatomical sites such as the stomach, lungs, cardiac muscle, cardiac blood or liver, but does not appear to intervene in other sites such as the brain or the vitreous humour.

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Authors and Affiliations

  1. Service de Médecine Légale, Faculté de Médecine, 27, boulevard Jean Moulin, 13385, Marseille, Cedex 5, France

    Anne-Laure Pélissier-Alicot & Georges Léonetti

  2. Laboratoire de Pharmacologie et Toxicologie, CHU Dupuytren, 2, avenue Martin Luther King, 87042, Limoges, Cedex, France

    Jean-Michel Gaulier, Carine Dupuis, Gérard Lachâtre & Pierre Marquet

  3. Centre de Formation et de Recherches Experimentales Médico-chirurgicales, Faculté de Médecine, 27, boulevard Jean Moulin, 13385, Marseille, Cedex 5, France

    Marc Feuerstein

  4. Laboratoire de Toxicologie, Faculté de Pharmacie, 2 rue du Docteur Marcland, 87025, Limoges, Cedex, France

    Gérard Lachâtre

Authors
  1. Anne-Laure Pélissier-Alicot
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  2. Jean-Michel Gaulier
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  3. Carine Dupuis
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  4. Marc Feuerstein
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  5. Georges Léonetti
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  6. Gérard Lachâtre
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  7. Pierre Marquet
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Correspondence to Anne-Laure Pélissier-Alicot.

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Pélissier-Alicot, AL., Gaulier, JM., Dupuis, C. et al. Post-mortem redistribution of three beta-blockers in the rabbit. Int J Legal Med 120, 226–232 (2006). https://doi.org/10.1007/s00414-005-0022-5

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  • DOI: https://doi.org/10.1007/s00414-005-0022-5

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