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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Contribution of lysosomes to concentrative uptake of DX-9065a into rat liver.

This study evaluates the distribution profile in tissues and concentrative uptake mechanism for a cationic compound of DX-9065a in rats. After a single intravenous dosing of [(14)C]-DX-9065a to male rats, higher levels of radioactivity were observed in kidney and liver. Moreover, the radioactivity in the liver continuously increased up to 6 h after intravenous dosing and a concentrative uptake of the drug against the radioactivity gradient between plasma and liver, showing K(p) value of 90. 7. In contrast, carrier-mediated systems did not play a significant role in the uptake of DX-9065a by hepatocytes. A subcellular distribution study was conducted by means of Percoll density gradient centrifugation and revealed a high affinity of the compound with the lysosomes. It was concluded that DX-9065a permeated into hepatocyte across the membrane primarily by passive diffusion, and the consequent process of lysosomal trapping played a major role in the concentrative uptake of the drug into the liver.[1]


  1. Contribution of lysosomes to concentrative uptake of DX-9065a into rat liver. Murayama, N., Nakaoka, M., Sudo, K. Journal of pharmaceutical sciences. (2006) [Pubmed]
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