Protein binding of phenytoin and lidocaine in pediatric patients with type I diabetes mellitus.
We evaluated serum protein binding of phenytoin and lidocaine, the extent of albumin and hemoglobin glycation, and alpha-1-acid glycoprotein concentrations in 47 children and adolescents (9-17 years) with type I diabetes mellitus (DM). Serum was incubated with phenytoin (n = 47) and lidocaine (n = 32) to yield total concentrations of 19.4 +/- 1.34 and 4.6 +/- 0.5 mg/l, respectively. A serum ultrafiltrate was prepared from an aliquot of each sample by membrane centrifugation. Total and free concentrations of phenytoin (free fraction 8.3 +/- 1.0%) and lidocaine (free fraction 25.8 +/- 11.6%) were determined using a fluorescence polarization immunoassay technique. A linear relationship (r = 0.63, p = 0.0001, y = 40.1 + [-0.2x]) was also found between the alpha-1-acid glycoprotein concentration (68.5 +/- 20.9 mg%, range 47.2-134.7 mg%) and lidocaine-free fraction (n = 32). No relationship existed between the extent of glycated albumin and the lidocaine-free fraction, in contrast to the linear correlation (r = 0.49, p = 0.0005, y = 3.7 + 0.4x) found between the extent of glycated albumin and the free fraction of phenytoin in serum (n = 47). A similar correlation (r = 0.49, p = 0.014, y = 3.7 + 0.3x) was found between glycated albumin (%) and the phenytoin-free fraction (3.9 +/- 0.9%) when examined in a separate (n = 17) set of patient samples spiked to contain a total serum phenytoin concentration of 32.6 +/- 1.4 (range 29.4-35.7) mg/l. Our data demonstrate a predictable increase in the free fraction of phenytoin as the extent of albumin glycation increases in pediatric patients with type I DM who are in poor glycemic control. This relationship was not found for lidocaine, a representative basic compound. These findings suggest that glycation of albumin alters the binding of phenytoin in children and adolescents with type I DM.
Kearns
G L
GL
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock.
Kemp
S F
SF
Turley
C P
CP
Nelson
D L
DL
D000293:Adolescent; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005260:Female; D006001:Glycoconjugates / Q000032:analysis; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D008012:Lidocaine / Q000378:metabolism*; D008297:Male; D009961:Orosomucoid / Q000032:analysis; D010672:Phenytoin / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000032:analysis
D006001:Glycoconjugates; D006454:Hemoglobins; D009961:Orosomucoid; D012709:Serum Albumin; D010672:Phenytoin; D008012:Lidocaine