Cocaine and Cocaethylene Binding to Human Liver

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.