Martin B R, Reynolds M L, Harris L S, Toro-Goyco E
Biochem Pharmacol. 1984 Feb 1;33(3):429-34. doi: 10.1016/0006-2952(84)90236-3.
The binding of [3H]phencyclidine (PCP) to rat serum and human plasma was studied using equilibrium dialysis. [3H]PCP bound with a relatively low affinity to both rat serum (KD = 1.5 X 10(-5) M) and human plasma (KD = 6.2 X 10(-6) M). However, the binding capacity was quite large for rat serum (5.7 nmoles/ml) and human plasma (5.6 nmoles/ml). Binding was readily reversible as shown by the efflux of [3H]PCP from a dialysis bag containing the rat serum-drug complex. In addition, the [3H]PCP-human serum complex appeared to dissociate completely when analyzed by Sephadex gel filtration chromatography. The low affinity of PCP for serum appeared to account in large part for the high tissue-to-plasma ratios that are observed in animals and humans injected with this drug. In vitro equilibration of [3H]PCP between rat serum and tissue homogenates resulted in at least a 10-fold accumulation of [3H]PCP in the homogenates. [3H]PCP was found to bind weakly to the major protein components of human serum (macroglobulins, immunoglobulins and albumins). The weak nature of the binding to serum proteins coupled with the relatively high capacity of binding probably account for the failure of other drugs to compete for PCP binding.
采用平衡透析法研究了[3H]苯环己哌啶（PCP）与大鼠血清及人血浆的结合情况。[3H]PCP与大鼠血清（KD = 1.5×10^(-5) M）和人血浆（KD = 6.2×10^(-6) M）的结合亲和力相对较低。然而，大鼠血清（5.7纳摩尔/毫升）和人血浆（5.6纳摩尔/毫升）的结合容量相当大。如[3H]PCP从含有大鼠血清 - 药物复合物的透析袋中流出所示，结合很容易逆转。此外，通过Sephadex凝胶过滤色谱分析时，[3H]PCP - 人血清复合物似乎完全解离。PCP对血清的低亲和力似乎在很大程度上解释了在注射该药物的动物和人类中观察到的高组织与血浆比率。[3H]PCP在大鼠血清和组织匀浆之间的体外平衡导致匀浆中[3H]PCP至少积累10倍。发现[3H]PCP与人血清的主要蛋白质成分（巨球蛋白、免疫球蛋白和白蛋白）结合较弱。与血清蛋白结合的弱性以及相对较高的结合容量可能解释了其他药物无法竞争PCP结合的原因。
