Valko Klara L, Zhang Tong
Bio-Mimetic Chromatography Ltd, Business & Technology Centre, Bessemer Drive, Stevenage, Herts SG1 2DX UK.
Chiral Technologies Europe, Parc d'Innovation 160, Bd Gonthier d'Andernach CS 80140 67404 ILLKIRCH CEDEX France.
ADMET DMPK. 2020 Jan 25;9(2):151-165. doi: 10.5599/admet.929. eCollection 2021.
Chloroquine and hydroxy-chloroquine already established as anti-malarial and lupus drugs have recently gained renewed attention in the fight against the Covid-19 pandemic. Bio-mimetic HPLC methods have been used to measure the protein and phospholipid binding of the racemic mixtures of the drugs. The tissue binding and volume of distribution of the enantiomers have been estimated. The enantiomers can be separated using Chiralpak AGP HPLC columns. From the α-1-acid-glycoprotein (AGP) binding, the lung tissue binding can be estimated for the enantiomers. The drugs have a large volume of distribution, showed strong and stereoselective glycoprotein binding, medium-strong phospholipid-binding indicating only moderate phospholipidotic potential, hERG inhibition and promiscuous binding. The drug efficiency of the compounds was estimated to be greater than 2 % which indicates a high level of free biophase concentration relative to dose. The biomimetic properties of the compounds support the well-known tolerability of the drugs.
氯喹和羟氯喹作为抗疟疾和狼疮药物早已为人所知，最近在抗击新冠疫情中重新受到关注。仿生高效液相色谱法已被用于测定这些药物外消旋混合物的蛋白质和磷脂结合情况。对映体的组织结合和分布容积已得到估算。使用Chiralpak AGP高效液相色谱柱可分离对映体。根据α-1-酸性糖蛋白（AGP）结合情况，可估算对映体在肺组织中的结合。这些药物分布容积大，显示出强烈且立体选择性的糖蛋白结合、中等强度的磷脂结合，表明只有中等程度的磷脂沉积潜力、人醚-去极化钾通道（hERG）抑制作用和杂乱结合。这些化合物的药物效率估计大于2%，这表明相对于剂量而言，游离生物相浓度较高。这些化合物的仿生特性支持了这些药物众所周知的耐受性。
