@article{oai:dwcla.repo.nii.ac.jp:00000759,
 author = {伊賀, 勝美 and IGA, Katsumi},
 journal = {総合文化研究所紀要, Bulletin of Institute for Interdisciplinary Studies of Culture Doshisha Women’s College of Liberal Arts},
 month = {Jul},
 note = {AN10052143-20130708-77, Hallifax and Houston have reported that cationic amphiphilic drugs such as quinine, propranolol, imipramine, fluvoxamine, and fluoxetin were taken up by rat hepatic cells both in saturable and non-saturable manners in in-vitro cellular uptake experiments. In this study, the reported profiles of the cellular uptake rate versus applied drug concerntration were simulated using a compartmental model, assuming eight compartments representing intra-cellular organelle and active transport systems on cellular membranes.
When it was assumed that an ionized molecule can be distributed into the lipid membranes (partition coefficient, P(i)) and that this ionized molecule can be transported into the cytosolic and lysosomal spaces by transporters expressed on the cellurar membrane and lysosomal membrane, respectively, the actual cellular uptake rate profiles were simulated successfully.
It was also found that the non-saturable distributions that had been reported to differ greatly among ths CADs were determined almost entirely by P(i) and that there was a strong correlation between P(i) nad pKa.
The ratios of the maximal cytosolic drug concentration to the incubation medium (f2/1, max) estimated for the CADs after the sumulations, to which attention should be paid in relation to the drug-drug interaction potential of metabolic inhibitors, accounted for a significantly high value ranging from 4 to 7. The value estimated for fluvoxamine (approximately 7) seemed to help explain the unusually large magnitudes of drug-drug interactions found in the concomitant administrations with fluvoxamine., 論文 (Article)},
 pages = {77--92},
 title = {カチオン性・両親媒性薬物 (CAD) の肝細胞への取り込み機構 : 能動輸送システムを仮定したコンパートメントモデルによるシミュレイション},
 volume = {30},
 year = {2013},
 yomi = {イガ, カツミ}
}