Serum Protein Binding of Phenytoin and Valproic Acid in Insulin-Dependent Diabetes Mellitus

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The serum protein binding of valproic acid (VPA) and phenytoin (PHT) was determined in spiked serum samples collected from 17 patients with insulin-dependent diabetes mellitus and 16 healthy control subjects. The free fraction of VPA was significantly greater in patients than in controls (7.6 ± 1.6% vs. 6.2 ± 1.2%, p < 0.01); for PHT, free fraction values were similar in the two groups (8.2 ± 1.1% vs. 8.4 ± 1.2%). The free fraction of VPA in diabetic patients was positively correlated with free fatty acid (FFA) concentration (r = 0.79, p < 0.01). No significant relationships could be found between free drug fraction and either serum albumin or glycosylated protein concentration.

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