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.Electronic supplementary material Supplementary material is available in the online version of this article at and accessible for authorised users.This work was presented in part at the 40th International Meeting of The International Association of Forensic Toxicologists, 26–30 August 2002, Paris, France, and at the 11th Annual Meeting of the Société Française de Toxicologie Analytique, 11–13 June 2003, Dinard, France.