The enantioselective binding of mefloquine enantiomers to P-glycoprotein determined using an immobilized P-glycoprotein liquid chromatographic stationary phase.
The enantioselective binding of mefloquine enantiomers to P-glycoprotein determined using an immobilized P-glycoprotein liquid chromatographic stationary phase.
复制标题
使用固定化 P-糖蛋白液相色谱固定相测定甲氟喹对映体与 P-糖蛋白的对映选择性结合。
DOI：
10.1023/a:1013098213770
复制
发表时间：
2001
影响因子：
3.7
通讯作者：
Wainer,IW
中科院分区：
文献类型：
--
作者：
Lu,L;Leonessa,F;Baynham,MT;Clarke,R;Gimenez,F;Pham,YT;Roux,F;Wainer,IW
甲氟喹（MQ），α-2-哌啶基-2，8-双（三氟甲基）-4-喹啉甲醇（图1），是一种广泛用于治疗氯喹耐药性疟疾的抗疟药（1）。该药剂作为赤式异构体（+）-[11 R，2S]-MQ {（+）-MQ}和（-）-[11 S，2 R]-MQ {（-）-MQ}的外消旋混合物给药。在人体中，MQ具有对映体选择性分布，血浆和脑中的（−）-MQ浓度较高（2，3）。MQ还显示出抑制药物外排转运蛋白P-糖蛋白（Pgp）的活性（4-7）。Shao等人证明，MQ增加了P388/ADR白血病细胞系中Pgp底物柔红霉素的细胞内蓄积（4）。此外，当MQ与Pgp-底物长春碱（VBL）同时使用时，这两种药物以非竞争性方式相互协同作用。
Mefloquine (MQ), α-2-piperidinyl-2, 8-bis (trifluoromethyl)-4-quinolinemethanol (Fig. 1), is an antimalarial agent widely used to treat chloroquine-resistant malaria (1). The agent is administered as a racemic mixture of erythroisomers,(+)-[11R, 2S]-MQ {(+)-MQ} and (−)-[11S, 2R]-MQ {(−)-MQ}. In humans, there is an enantioselective distribution of MQ with higher plasma and brain concentrations of (−)-MQ (2, 3).MQ has also been shown to inhibit the activity of the drug efflux transporter P-glycoprotein (Pgp)(4–7). Shao et al. demonstrated that MQ increased the intracellular accumulation of the Pgp substrate daunomycin in the P388/ADR leukemia cell line (4). In addition, when MQ was used concomitantly with the Pgp-substrate vinblastine (VBL), the two agents interacted with each other synergistically in a noncompetitive manner.