Koyama H, Sugioka N, Uno A, Mori S, Nakajima K
Department of Hospital Pharmacy, Kyoto Prefectural University of Medicine, Japan.
J Pharm Pharmacol. 1999 Sep;51(9):1009-14. doi: 10.1211/0022357991773474.
To determine whether biological maturation influences the kinetics of carbamazepine-serum protein binding, the carbamazepine free fraction (%) was investigated in the serum of 66 patients, ranging from 4 to 83 years, with epilepsy or trigeminal neuralgia, treated with carbamazepine alone or carbamazepine in combination with phenytoin, phenobarbital, and/or valproic acid, over a relatively long period. Biochemical parameters such as levels of albumin and non-glycated albumin showed a significant relationship with carbamazepine free fraction (r = -0.521, P < 0.001 for albumin; r = -0.700, P < 0.001 for non-glycated albumin). Non-glycated albumin was more strongly correlated with carbamazepine free fraction. The biochemical parameters showed a significant relationship with age (r =-0.243, P < 0.1 for albumin; r =0.666, P < 0.001 for glycated albumin; r = -0.459, P < 0.001 for non-glycated albumin; r = 0.640, P < 0.001 for carbamazepine free fraction). Glycated albumin (%), non-glycated albumin and carbamazepine free fraction (%) were strongly correlated with age, whereas albumin showed only a weak correlation with age. To evaluate the effects of ageing on carbamazepine-serum protein binding, the patients were divided into three groups according to age: children, 4-15 years; adults, 16-64 years; elderly, 65-83 years. Albumin and non-glycated albumin were much lower, and glycated albumin (%) and carbamazepine free fraction (%) much higher in the elderly group than in the other two groups. The results of this study showed that the major ligand of carbamazepine in the serum was non-glycated albumin, which decreased with age. These observations suggested that in elderly patients, the elevation of free carbamazepine concentrations in the serum caused by reduced non-glycated albumin levels, induces increases in the sensitivity of the pharmacological effects of carbamazepine and the risk of drug interactions.
为了确定生物成熟度是否会影响卡马西平与血清蛋白结合的动力学，我们对66例年龄在4岁至83岁之间、患有癫痫或三叉神经痛、单独使用卡马西平或卡马西平与苯妥英钠、苯巴比妥和/或丙戊酸联合治疗的患者血清中的卡马西平游离分数（%）进行了较长时间的研究。白蛋白和非糖化白蛋白水平等生化参数与卡马西平游离分数显示出显著相关性（白蛋白：r = -0.521，P < 0.001；非糖化白蛋白：r = -0.700，P < 0.001）。非糖化白蛋白与卡马西平游离分数的相关性更强。这些生化参数与年龄也显示出显著相关性（白蛋白：r = -0.243，P < 0.1；糖化白蛋白：r = 0.666，P < 0.001；非糖化白蛋白：r = -0.459，P < 0.001；卡马西平游离分数：r = 0.640，P < 0.001）。糖化白蛋白（%）、非糖化白蛋白和卡马西平游离分数（%）与年龄密切相关，而白蛋白与年龄仅呈弱相关。为了评估衰老对卡马西平与血清蛋白结合的影响，根据年龄将患者分为三组：儿童组，4 - 15岁；成人组，16 - 64岁；老年组，65 - 83岁。老年组的白蛋白和非糖化白蛋白水平明显低于其他两组，而糖化白蛋白（%）和卡马西平游离分数（%）则明显高于其他两组。本研究结果表明，血清中卡马西平的主要配体是非糖化白蛋白，其含量随年龄增长而降低。这些观察结果表明，在老年患者中，非糖化白蛋白水平降低导致血清中游离卡马西平浓度升高，从而增加了卡马西平药理作用的敏感性和药物相互作用的风险。
