Pharmacokinetics of valproic acid in young and elderly subjects.

Abstract

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.

Pharmacokinetics of valproic acid in the elderly.

“…The discrepancies between our findings and those reported in the previous study cannot be explained by differences in route of administration: in fact, VPA is known to be completely absorbed from the gastro-intestinal tract in young subjects (Perucca et al, 1978a, b) and a possible reduction of bioavailability in the elderly would have resulted in overestimation rather than underestimation of its volume of distribution. On inspection of the data presented by Bryson et al (1983) it is also unlikely that differences in type of kinetic analysis (calculation of Vd s, or volume of distribution at steady-state, rather than Vd) could account for the observed discrepancies. It can be concluded that the latter were probably related to the characteristics of the populations investigated: it is unclear, for example, whether the elderly patients included in the earlier study were ambulant or bedridden and whether they were receiving associated drug therapy (although it was stated that none was taking drugs 'likely to interact' with VPA).…”

“…Differences between the control groups (e.g. in alcohol intake) should be considered, especially in view of the fact that the young volunteers included in the Bryson et al (1983) study showed unusually short VPA halflives.…”

“…Valproic acid (VPA) is a broad spectrum antiepileptic drug which is widely used in all age groups and for which significant pharmacokinetic changes have recently been described in elderly patients (Bryson et al, 1983).…”

Peculiarity of Epilepsy in Elderly People: A Review

“…Valproate does not induce hepatic enzymes but it is associated with reduction in bone mineral density through reduction in osteoblastic function. 35,36,43 Its other important side effects in the elderly include dosedependent tremor and reversible parkinsonism.…”

Evidence-Based Pharmacological Treatment of Geriatric Bipolar Disorder

“…With increased age, the elimination half-life of VAL can be prolonged [42], and the free fraction of plasma concentrations increases [43]. Aspirin can increase the VAL free fraction [44].…”