Affiliation:
1. Department of Hospital Pharmacy, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 6020841, Japan
2. Department of Pharmaceutics and Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607, Japan
3. Department of Neurology and Gerontology, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 6020841, Japan
Abstract
Abstract
To determine whether biological maturation influences the kinetics of carbamazepineserum 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.
Publisher
Oxford University Press (OUP)
Subject
Pharmaceutical Science,Pharmacology
Cited by
18 articles.
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