Apparent clearance of valproic acid in elderly epileptic patients: estimation of the confounding effect of albumin concentration

BACKGROUND Valproic acid (VPA) apparent clearance (CL) estimated from total serum concentrations is analogous in elderly and non-elderly adult patients. As drug-protein binding decreases in old age, the aim of our study was to evaluate the confounding effect of the serum albumin concentration on the VPA apparent CL in elderly patients. METHODS In 102 epileptic out-patients treated with VPA in monotherapy, serum total steady-state trough concentrations (Css) were determined. Css concentrations were normalized for a 42 g/L albumin concentration (Css(N)), and the apparent CL and normalized apparent CL(N) were calculated. RESULTS A poor concordance of 53% was found in the classification of Css and Css(N) levels of VPA as subtherapeutic, therapeutic, or supratherapeutic dose. In the elderly (≥65 years) and non-elderly adult patients, the VPA apparent CL was similar; however, normalized apparent CL(N) was significantly lower in older patients (P < 0.01), with a 40% median decrease. CONCLUSIONS Total VPA concentrations should be interpreted with caution, mainly in older patients, in which determination of unbound or normalized total drug concentrations may be clinically useful. Normalization of total concentrations permits an estimation of the masking effect of serum albumin concentrations on the VPA apparent CL in elderly patients.