Effects of dosage, excess weight and gender on pharmacokinetics of sodium valproate sustained release dosage form in patients with neuro-psychiatric disorders

Abstract

To determine the effects of dosage, excess weight and gender on pharmacokinetics of sodium valproate in patients with neuro-psychiatric disorders age ranged from 18 to 60 years old. The study design was open label, multiple dose, paralleled prospective study. The study could be divided into three parts as follow: First, the impact of different dosages (500 mg/day versus 1000 mg/day) of sustained release formulation on valproate clearance and plasma concentration were studied in psychiatric patients; analysis based on routine therapeutic drug monitoring data. The results have shown both consistent and contrast to previous studies reported. Mean of total concentration increased disproportionately with the increase in dosage, while free concentration increased proportionately. Moreover, higher clearance of total VPA while no difference in clearance of free VPA were found in patients receiving VPA 1000 mg/day as compared to patients receiving 500 mg/day of VPA. Free VPA concentration was proposed to be a more suitable parameter for future therapeutic level monitoring and the targeted level was proposed to be 4-12 mg/l. Second, the effects of gender and excess weight on VPA pharmacokinetics were demonstrated. Female with excess weight showed significantly lower in both clearances of total and free VPA, the effect of excess weight on VPA pharmacokinetics was less obvious in male. Third, predictive equations for total and free VPA concentrations and clearances from general demographic characteristics of patients, such as, dosage, gender, age, body weight, etc. have been generated. These predictive factors account for approximately 60% of the variances.