Contribution of lysosomes to concentrative uptake of DX‐9065a into rat liver
Identifieur interne : 001D55 ( Main/Exploration ); précédent : 001D54; suivant : 001D56Contribution of lysosomes to concentrative uptake of DX‐9065a into rat liver
Auteurs : Nobuyuki Murayama [Japon] ; Minoru Nakaoka [Japon] ; Kenichi Sudo [Japon]Source :
- Journal of Pharmaceutical Sciences [ 0022-3549 ] ; 2006-08.
English descriptors
- Teeft :
- American pharmacists association, August, Basic drugs, Cationic, Cationic compound, Cationic drug, Cationic drugs, Cell membrane, Certain tissues, Chemical structure, Chloroquine, Concentration dependency, Concentration dependency range, Concentrative, Concentrative uptake, Cumulative manner, Determinant factor, Direct factor, Dosing, Enzyme activities, Extracellular compartment, Hepatocytes, Incubation periods, Inhibitor, Intravenous administration, Intravenous dosing, Kaleidagraphtm software, Kinetic parameters, Lipid bilayer, Liquid scintillation, Liver homogenate, Lysosomal, Lysosomal fraction, Lysosomal inhibitors, Lysosome, Major role, Major route, Male rats, Marker enzyme, Metabolic inhibitors, Mitochondrial fraction, Murayama, Naga activity, Nonionic form, Nuclear fraction, Organic cations, Passive diffusion, Pharm, Pharmaceutical, Pharmaceutical sciences, Pharmacol, Present report, Present study, Protein concentration, Radioactivity, Radioactivity concentration, Radioactivity concentration gradient, Radioactivity level, Radioactivity uptake, Small portion, Solid line, Statistical analysis, Subcellular, Subcellular distribution, Temperature dependency, Thromb haemost, Time course, Time points, Tissue distribution, Uptake, Urine samples.
Abstract
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 [14C]‐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 Kp 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. © 2006 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1763–1770, 2006
Url:
DOI: 10.1002/jps.20530
Affiliations:
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After a single intravenous dosing of [14C]‐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 Kp 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. © 2006 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1763–1770, 2006</div></front></TEI><affiliations><list><country><li>Japon</li></country><region><li>Région de Kantō</li></region><settlement><li>Tokyo</li></settlement></list><tree><country name="Japon"><region name="Région de Kantō"><name sortKey="Murayama, Nobuyuki" sort="Murayama, Nobuyuki" uniqKey="Murayama N" first="Nobuyuki" last="Murayama">Nobuyuki Murayama</name></region><name sortKey="Murayama, Nobuyuki" sort="Murayama, Nobuyuki" uniqKey="Murayama N" first="Nobuyuki" last="Murayama">Nobuyuki Murayama</name><name sortKey="Nakaoka, Minoru" sort="Nakaoka, Minoru" uniqKey="Nakaoka M" first="Minoru" last="Nakaoka">Minoru Nakaoka</name><name sortKey="Sudo, Kenichi" sort="Sudo, Kenichi" uniqKey="Sudo K" first="Kenichi" last="Sudo">Kenichi Sudo</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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