Virtanen R, Iisalo E, Irjala K
Acta Pharmacol Toxicol (Copenh). 1982 Aug;51(2):159-64. doi: 10.1111/j.1600-0773.1982.tb01008.x.
The protein binding of doxepin (DOX) and desmethyldoxepin (DDOX) were studied in serum and plasma samples from healthy volunteers and psychiatric patients. Binding was measured by equilibrium dialysis (16 hrs at 37 degrees) and drug concentrations by radioimmunoassay. In addition, albumin and alpha 1-acid glycoprotein concentrations of the samples were measured by radial immunodiffusion. The mean +/- SEM percentages of unbound DOX were: 20.4 +/- 1.2 and 15.9 +/- 1.2 in healthy subjects (n = 16) and patients (n = 15) respectively, and those of DDOX: 21.4 +/- 0.9 and 19.0 +/- 1.4 for healthy subjects and patients, respectively. There was a significant negative correlation between serum alpha 1-acid glycoprotein concentration and free fraction of DOX in both groups. In healthy subjects a significant negative correlation was also found between albumin concentrations and free fraction of both DOX and DDOX. Binding experiments with isolated protein fractions revealed that all of the total binding in plasma could be explained by binding to albumin and alpha 1-acid glycoprotein. The observed 2--4-fold interindividual variability in the free fractions of these drugs is probably less important than the much larger variability in the total serum concentrations.
在健康志愿者和精神科患者的血清和血浆样本中研究了多塞平（DOX）和去甲多塞平（DDOX）的蛋白结合情况。通过平衡透析法（37℃下16小时）测定结合情况，通过放射免疫分析法测定药物浓度。此外，通过放射免疫扩散法测定样本中白蛋白和α1-酸性糖蛋白的浓度。未结合DOX的平均±标准误百分比分别为：健康受试者（n = 16）中为20.4±1.2，患者（n = 15）中为15.9±1.2；DDOX的分别为：健康受试者和患者中分别为21.4±0.9和19.0±1.4。两组中血清α1-酸性糖蛋白浓度与DOX的游离分数之间均存在显著负相关。在健康受试者中，白蛋白浓度与DOX和DDOX的游离分数之间也发现显著负相关。对分离的蛋白组分进行的结合实验表明，血浆中的所有总结合都可以通过与白蛋白和α1-酸性糖蛋白的结合来解释。这些药物游离分数中观察到的个体间2至4倍的变异性可能不如总血清浓度中更大的变异性重要。
