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/1, 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-l-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/1. 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 glycémie 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.

Keywords:
Diabetes, Protein binding, Phenytoin, Lidocaine
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1988
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