Post-mortem redistribution of three beta-blockers in the rabbit.
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.
Pélissier-Alicot
Anne-Laure
AL
Service de Médecine Légale, Faculté de Médecine, 27 boulevard Jean Moulin, 13385 Marseille Cedex 5, France. apelissier@ap-hm.fr
Gaulier
Jean-Michel
JM
Dupuis
Carine
C
Feuerstein
Marc
M
Léonetti
Georges
G
Lachâtre
Gérard
G
Marquet
Pierre
P
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D000818:Animals; D001262:Atenolol / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D053593:Forensic Toxicology; D008401:Gas Chromatography-Mass Spectrometry; D007262:Infusions, Intravenous; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D023421:Models, Animal; D011180:Postmortem Changes; D011433:Propranolol / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D011817:Rabbits; D014018:Tissue Distribution
D000319:Adrenergic beta-Antagonists; D001262:Atenolol; D011433:Propranolol; D008790:Metoprolol