可卡因和可口卡因与人类肝脏的结合

Cocaine and cocaethylene binding to human liver.

作者信息

Bailey D N

机构信息

Department of Pathology, University of California Medical Center, San Diego 92103-8320, USA.

出版信息

J Anal Toxicol. 1998 Sep;22(5):355-8. doi: 10.1093/jat/22.5.355.

DOI:10.1093/jat/22.5.355

PMID:9737328

Abstract

The binding of cocaine (COC) and cocaethylene (CE) to whole human liver homogenates in vitro was studied by equilibrium dialysis. Drugs were measured by high-pressure liquid chromatography. Up to 32% of COC and up to 43% of CE were bound. Scatchard analysis suggested a high-affinity, low-capacity binder for both COC (Ka, 4.69 x 10(4) L/mol; Bo, 1.08 x 10(-5) mol/L) and CE (Ka, 4.38 x 10(4) L/mol; Bo, 1.54 x 10(-5) mol/L). In addition, low-affinity, high-capacity binders for COC (Ka, 2.93 x 10(3) L/mol; Bo, 1.32 x 10(-4) mol/L) and CE (Ka, 6.50 x 10(3) L/mol; Bo, 1.11 x 10(-4) mol/L) were noted. Finally, for both compounds, very low-affinity, high-capacity binding, which was likely nonspecific in nature, was defined as follows: COC, Ka, 8.00 x 10(2) L/mol; Bo, 5.45 x 10(-4) mol/L and CE, Ka, 2.10 x 10(3) L/mol; Bo, 3.71 x 10(-4) mol/L. The binding profiles of COC and CE in liver were compared with those in human serum and placenta studied previously by this laboratory.

摘要

采用平衡透析法研究了可卡因（COC）和可口卡因（CE）在体外与全人类肝脏匀浆的结合情况。通过高压液相色谱法测定药物含量。结果显示，高达32%的COC和高达43%的CE会发生结合。Scatchard分析表明，COC（Ka，4.69×10⁴L/mol；Bo，1.08×10⁻⁵mol/L）和CE（Ka，4.38×10⁴L/mol；Bo，1.54×10⁻⁵mol/L）均有高亲和力、低容量的结合物。此外，还发现了COC（Ka，2.93×10³L/mol；Bo，1.32×10⁻⁴mol/L）和CE（Ka，6.50×10³L/mol；Bo，1.11×10⁻⁴mol/L）的低亲和力、高容量结合物。最后，对于这两种化合物，定义了亲和力极低、容量高的结合情况，其可能本质上是非特异性的：COC，Ka，8.00×10²L/mol；Bo，5.45×10⁻⁴mol/L；CE，Ka，2.10×10³L/mol；Bo，3.71×10⁻⁴mol/L。本实验室将肝脏中COC和CE的结合情况与之前研究的人血清和胎盘中的结合情况进行了比较。