Factors Influencing the Serum Concentration of Antiepileptic Drugs-Relationship between the Serum Valproic Acid Concentration and Daily Dose in Epileptic Patients.:Relationship between the Serum Valproic Acid Concentration and Daily Dose in Epileptic Patients

The relation between the serum valproic acid (VPA) concentration and the daily dose was studied using the therapeutic drug monitoring data obtained from epileptic patients who were treated with the oral administration of the sustained-release preparations of VPA. The 233 data at steady-state after repetitive dosing were used.A multiple regression analysis revealed the serum VPA concentration to be dependent on only one variable regarding the daily dose per ideal body weight.An 1-compartment model including two assumptions that VPA binds to plasma protein and the distribution volume of VPA is proportional to the ideal body weight, was postulated for this analysis. The plasma protein binding ratios were calculated based on the values estimated by the nonlinear least squares method and they were found to be 96.0, 94.7, 92.6 (%) when the serum VPA concentrations were 40, 70, 100 (μg/mL), respectively. These values showed a good correlation with those reported by previous investigators and this model also seemed to demonstrate good confidence level.