Significance of lipoproteins in serum binding variations of amitriptyline, nortriptyline, and quinidine
Significance of lipoproteins in serum binding variations of amitriptyline, nortriptyline, and quinidine
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脂蛋白在阿米替林、去甲替林和奎尼丁血清结合变异中的意义
DOI：
10.1038/clpt.1982.209
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发表时间：
1982
影响因子：
6.7
通讯作者：
P. K. Lunde
中科院分区：
文献类型：
--
作者：
E. Pike;B. Skuterud;P. Kierulf;P. K. Lunde
应用同位素技术，通过平衡透析法测定了阿米替林（AT）、去甲替林（NT）和奎尼丁（Q）与不同脂蛋白含量血清的结合率。从10名空腹受试者中获得血清，这些受试者的胆固醇、甘油三酯或两者水平正常至显著升高。当通过标准超离心技术从8份血清中去除脂蛋白时，结合/未结合（B/F）AT的比率平均降低47%（范围30%至68%），NT平均降低54%（范围39%至67%），Q平均降低6%（范围0至16%）。B/F比值的降低与AT（r = 0.88）和NT（r = 0.82）的胆固醇和甘油三酯血清浓度之和呈线性相关，但与Q（r = 0.15）无关。在用8种不同浓度（范围为原始含量的0 - 100%）的脂蛋白重悬的3份去脂蛋白血清中，AT和NT与脂蛋白的比值B/F之间存在线性相关性，如胆固醇或甘油三酯浓度所证明（r = 0.97 - 0.99），但与Q无关（r =-0.17至0.36）。最后，在最初的10份血清样本中，AT（r = 0.89）和NT（r = 0.68）的比值B/F与血清脂蛋白（胆固醇和甘油三酯的总和）之间存在线性相关性，而Q（r =-0.15）则没有这种关系。这些数据表明，基础药物的结合特性不同（可能取决于亲脂性）。
Using isotope technique, the serum binding of amitriptyline (AT), nortriptyline (NT), and quinidine (Q) was measured by equilibrium dialysis in sera containing varying amounts of lipoproteins. Sera were obtained from 10 fasting subjects with normal to grossly elevated levels of cholesterol, triglycerides, or both. When the lipoproteins were removed from eight of the sera by a standard ultracentrifugation technique, the ratio bound/unbound (B/F) AT decreased an average of 47% (range 30% to 68%), NT an average of 54% (range 39% to 67%), and Q an average of 6% (range 0 to 16%). This decrease in the ratio B/F correlated linearly with the sum of serum concentrations of cholesterol and triglycerides for AT (r = 0.88) and NT (r = 0.82), but not for Q (r = 0.15). In three lipoprotein‐depleted sera resuspended with lipoproteins at eight different concentrations ranging from 0 to 100% of the original content, there was a linear correlation between the ratio B/F for AT and NT and the lipoproteins, as evidenced by cholesterol or triglycerides concentrations (r = 0.97 to 0.99), but not for Q (r = ‐0.17 to 0.36). Finally, in the original 10 serum samples, there was a linear correlation between the ratio B/F and the serum lipoproteins (sum of cholesterol and triglycerides) for AT (r = 0.89) and NT (r = 0.68), whereas there was no such relationship for Q (r = ‐0.15). These data indicate that basic drugs differ in binding characteristics (probably depending on lipophility).