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The normal liver sinusoidal endothelium is thin and punctuated with fenestrations 50-200 nm in diameter that filter endobiotics and xenobiotics. Defenestration of the liver sinusoidal endothelium in old age and after pre-treatment with poloxamer-407 (P407) has been shown to prevent the transfer of small chylomicrons across the liver sinusoidal endothelium. The aim of this study was to investigate the impact of liver sinusoidal endothelium fenestrations on the hepatic uptake of the highly protein-bound drug diazepam. We hypothesized that defenestration will reduce the hepatic extraction of drugs which are highly bound to albumin.

The Influence of Old Age and Poloxamer-407 on the Hepatic Disposition of Diazepam in the Isolated Perfused Rat Liver