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.