Age-related alteration of carbamazepine-serum protein binding in man.
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.
Koyama
H
H
Department of Hospital Pharmacy, Kyoto Prefectural University of Medicine, Japan.
Sugioka
N
N
Uno
A
A
Mori
S
S
Nakajima
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000927:Anticonvulsants / Q000378:metabolism / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004049:Diethylcarbamazine / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D016014:Linear Models; D016859:Lipoxygenase Inhibitors / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008875:Middle Aged; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism*; D009961:Orosomucoid / Q000378:metabolism; D010634:Phenobarbital / Q000378:metabolism / Q000627:therapeutic use; D010672:Phenytoin / Q000378:metabolism / Q000627:therapeutic use; D012709:Serum Albumin / Q000378:metabolism*
D000927:Anticonvulsants; D016859:Lipoxygenase Inhibitors; D009961:Orosomucoid; D012709:Serum Albumin; D010672:Phenytoin; D004049:Diethylcarbamazine; D010634:Phenobarbital