Okudaira K, Sawada Y, Sugiyama Y, Iga T, Hanano M
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
J Pharmacobiodyn. 1989 Jan;12(1):24-30. doi: 10.1248/bpb1978.12.24.
Effect of quinidine on the hepatic uptake of digoxin was studied using isolated guinea pig hepatocytes and with the multiple indicator dilution method using perfused livers. The initial uptake rate of digoxin by isolated hepatocytes was significantly (p less than 0.05) decreased in the presence of quinidine or ouabain and at low temperature (27 degrees C). The influx rate constant to the liver (K1) of unbound digoxin was also decreased by quinidine or the metabolic inhibitor 2,4 dinitrophenol (DNP) in isolated perfused livers, while K1 of diazepam, which is thought to be taken up by a passive transport system, was not significantly changed in the presence of DNP. These findings suggest that an active transport system for digoxin may exist in the liver and may be inhibited by quinidine. We concluded that the quinidine-induce decreases in the hepatic distribution of digoxin may be attributed both to the decreased tissue binding and to the inhibition of uptake, which might be related to the decreased hepatic clearance.
使用分离的豚鼠肝细胞以及采用灌注肝脏的多指示剂稀释法，研究了奎尼丁对地高辛肝脏摄取的影响。在存在奎尼丁或哇巴因以及低温（27摄氏度）的情况下，分离的肝细胞对地高辛的初始摄取率显著降低（p小于0.05）。在分离的灌注肝脏中，奎尼丁或代谢抑制剂2,4-二硝基苯酚（DNP）也会降低未结合地高辛进入肝脏的流入速率常数（K1），而被认为通过被动转运系统摄取的地西泮的K1在存在DNP的情况下没有显著变化。这些发现表明，肝脏中可能存在地高辛的主动转运系统，并且可能被奎尼丁抑制。我们得出结论，奎尼丁诱导的地高辛肝脏分布减少可能归因于组织结合减少和摄取抑制，这可能与肝脏清除率降低有关。
