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

✍ Scribed by Nobuyuki Murayama; Minoru Nakaoka; Kenichi Sudo

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 179 KB
• Volume: 95
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.20530

✦ Synopsis

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.