Alteration of phenytoin binding by glycosylation of albumin in IDDM.
We measured glycosylated albumin and hemoglobin and serum protein binding of phenytoin in 57 children and adolescents with insulin-dependent diabetes mellitus (IDDM). Serum was incubated with phenytoin to yield concentrations of 15 and 25 mg/L, and a serum ultrafiltrate was prepared from an aliquot of each sample. We observed a linear correlation between glycosylated albumin and the free fraction of phenytoin at serum phenytoin concentrations of 15 mg/L (r = .35, P = .03) and 25 mg/L (r = .40, P = .003). A better correlation existed between the free fraction of phenytoin and total albumin concentrations for both serum concentrations (r = .45, P = .005 for 15 mg/L; r = .56, P = 10-5) for 25 mg/L), whereas the best linear correlation resided between the free fraction of phenytoin and the concentration of nonglycosylated albumin (r = .54, P = .0005 for 15 mg/L; r = .63, P less than 10(-6) for 25 mg/L). There was no correlation between the free fraction of phenytoin and the concentration of glycosylated albumin. Incubation of solutions of glycosylated and nonglycosylated albumin demonstrated significantly lower binding to the glycosylated fraction (P = 8.1 X 10(-6)). These results indicate that glycosylation of albumin diminishes the affinity of the phenytoin binding site on albumin. This alteration may have clinical significance in that it may alter the disposition of phenytoin in patients with IDDM and produce free phenytoin serum concentrations that are not accurately reflected by total serum phenytoin concentrations.
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000378:metabolism*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008297:Male; D010672:Phenytoin / Q000097:blood / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000032:analysis / Q000378:metabolism*
D006442:Glycated Hemoglobin; D010672:Phenytoin; D012709:Serum Albumin