Bailey D N
Department of Pathology, University of California, San Diego, USA.
Am J Clin Pathol. 1998 Oct;110(4):491-4. doi: 10.1093/ajcp/110.4.491.
The binding of cocaine and its ethyl analog, cocaethylene, to human milk was studied using equilibrium dialysis at 4 degrees C. For cocaine, a low-affinity, high-capacity binder was noted (equilibrium constant of association, Ka, 3.12 x 10(3) L/mol; concentration of binding sites, B0, 3.85 x 10(-4) mol/L), as well as a very low affinity, high-capacity binder (Ka, 7.54 x 10(2) L/mol; B0, 1.42 x 10(-3) mol/L). For cocaethylene, 2 low-affinity, high-capacity binders were suggested: a stronger (Ka, 3.79 x 10(3) L/mol; B0, 3.27 x 10(-4) mol/L) and a weaker (Ka, 1.84 x 10(3) L/mol; B0, 8.91 x 10(-4) mol/L) binder The low-affinity, high-capacity binder for cocaine and cocaethylene seems to be albumin, while the weaker nonspecific binding may be due to lipids. Up to 55% of cocaine and up to 61% of cocaethylene were bound to milk; such binding, coupled with the lower pH of milk (6.9) relative to that of serum (7.4), may enhance the mammary secretion of these 2 basic drugs, having important consequences for the nursing infant.
采用4℃平衡透析法研究了可卡因及其乙基类似物——可卡乙碱与人乳的结合情况。对于可卡因，发现了一种低亲和力、高容量结合物（缔合平衡常数Ka为3.12×10³L/mol；结合位点浓度B₀为3.85×10⁻⁴mol/L），以及一种极低亲和力、高容量结合物（Ka为7.54×10²L/mol；B₀为1.42×10⁻³mol/L）。对于可卡乙碱，提示有2种低亲和力、高容量结合物：一种较强的（Ka为3.79×10³L/mol；B₀为3.27×10⁻⁴mol/L）和一种较弱的（Ka为1.84×10³L/mol；B₀为8.91×10⁻⁴mol/L）结合物。可卡因和可卡乙碱的低亲和力、高容量结合物似乎是白蛋白，而较弱的非特异性结合可能归因于脂质。高达55%的可卡因和高达61%的可卡乙碱与乳汁结合；这种结合，再加上乳汁的pH值（6.9）相对于血清（7.4）较低，可能会增加这2种碱性药物的乳腺分泌，对哺乳期婴儿产生重要影响。
