Single-dose model for predicting steady-state valproic acid serum concentrations in seizure patients

Valproic acid serum concentrations predicted by a single-dose prediction model were compared with steady-state serum concentrations measured after the start of therapy in seizure patients. Ten patients receiving valproic acid for the first time or who had not been taking the drug for two or more weeks were entered into the study. The patients' therapies were initiated with the prescribed doses of valproic acid and then maintained on fixed doses and dosing intervals until steady-state trough serum samples were obtained. Initial 5-ml blood samples were collected six to 14 hours after the ingestion of the first dose; a 5-ml steady-state trough sample was drawn in the same manner three to seven days later. Both free and total drug concentrations were determined within 48 hours of sample collection using gas-liquid chromatography. The elimination rate constant was estimated from age-specific population half-life values found in the literature. Six patients (five children, aged four to 16 years) and one adult (aged 87 years) completed the study. There was a statistically significant correlation between predicted and measured steady-state valproic acid serum concentrations for both free and total concentrations. The single-dose prediction model accurately predicted steady-state valproic acid serum concentrations in these seizure patients.