A graphical nomogram method for predicting toxic concentrations of unbound phenytoin
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1Department of Clinical Pharmacology, Charles University of Prague, Czech Republic.
Abstract:
The graphical nomogram method to estimate the phenytoin free concentration at any selected total serum phenytoin and/or albumin concentrations was applied using Scatchard binding equation. The binding parameters were calculated by the non-linear least-squares regression analysis of the binding data collected from 96 outpatients on common anticonvulsant therapy. Free phenytoin concentration was measured by the Amicon multi-micro ultrafiltration system. The mean values of N and Kapp were found to be: N = 1.03, and Kapp = 18,500 (M-1). Correlation coefficient for relationship between measured and predicted free phenytoin concentrations was very good (r = 0.94), but the results of prediction-error analysis (MPE = 0.153, and RMSE = 0.296) show that the nomogram method overpredicts the measured free phenytoin (PHT) concentration approximately about 10% higher (15-30 mg/l) than serum phenytoin levels.