Pharmacokinetics of valproic acid in young and elderly subjects

The disposition of valproic acid was studied following single dose intravenous administration in seven young male volunteers aged 20-35 years and six elderly male in-patients aged 75-87 years. Following administration of 400 mg sodium valproate, blood samples were collected for 48 h and valproic acid concentrations analysed by enzymatic immunoassay. The median elimination half-life was 7.2 h in the young subjects but 14.9 h in the elderly patients (P less than 0.01). However, clearance did not differ significantly between groups, the values for young and old being 0.69 and 0.58 1/h respectively. The prolonged half-life resulted from a greater volume of distribution in the elderly. The median values (1/kg) for young and old were 0.13 and 0.19 respectively (P less than 0.01). These pharmacokinetic changes are unlikely to be of clinical importance.