Torres I, Suárez E, Rodríguez-Sasiain J M, Aguirre C, Calvo R
Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Leioa, Vizcaya, Spain.
Eur J Drug Metab Pharmacokinet. 1995 Apr-Jun;20(2):107-11. doi: 10.1007/BF03226363.
Protein binding of mianserin and imipramine in vitro was determined in sera from 10 patients with cancer and from 28 drug-free normal subjects. alpha 1-acid glycoprotein (AAG) concentrations ranged from 0.91 +/- 0.04 g/l in control subjects to 2.17 +/- 0.18 g/l in cancer patients. Albumin concentrations ranged from 55.80 +/- 1.68 g/l in control subjects to 39.71 +/- 4.40 g/l, respectively. Serum samples containing concentrations of 100 ng/ml for mianserin and 500 ng/ml for imipramine were ultrafiltered and the free concentration were measured with scintillation spectrophotometer. The mean free percentage of mianserin was significantly less in patients with cancer (8.70 +/- 0.29% in patients vs 14.30 +/- 0.50% in control subjects P < 0.001). A multiple regression analysis revealed a significant contribution of plasma AAG (r2 = 0.56, P < 0.01), but not of albumin to the overall variability in mianserin binding. No correlation was observed between protein binding of imipramine and AAG concentrations in serum of cancer patients. No significant changes were observed for protein binding of imipramine in cancer patients as compared with control subjects. Our results suggest that for antidepressant (AD) drugs, of which the binding depends on AAG, variability in protein binding could be expected in cancer patients. Thus, in cancer therapy, changes in analgesic doses could be necessary with this kind of antidepressant drug.
在来自10名癌症患者和28名未服用药物的正常受试者的血清中，对米安色林和丙咪嗪的体外蛋白结合情况进行了测定。α1-酸性糖蛋白（AAG）浓度在对照组受试者中为0.91±0.04 g/l，在癌症患者中为2.17±0.18 g/l。白蛋白浓度在对照组受试者中分别为55.80±1.68 g/l和39.71±4.40 g/l。对含有100 ng/ml米安色林和500 ng/ml丙咪嗪的血清样本进行超滤，并使用闪烁分光光度计测量游离浓度。米安色林的平均游离百分比在癌症患者中显著更低（患者为8.70±0.29%，对照组受试者为14.30±0.50%，P<0.001）。多元回归分析显示血浆AAG对米安色林结合的总体变异性有显著贡献（r2 = 0.56，P<0.01），但白蛋白没有。在癌症患者血清中，未观察到丙咪嗪的蛋白结合与AAG浓度之间存在相关性。与对照组受试者相比，癌症患者中丙咪嗪的蛋白结合未观察到显著变化。我们的结果表明，对于结合取决于AAG的抗抑郁药，癌症患者中蛋白结合可能存在变异性。因此，在癌症治疗中，使用这类抗抑郁药可能需要调整镇痛剂量。
