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. 2012 Mar;117(1):41-6.
doi: 10.3109/03009734.2011.640412. Epub 2011 Dec 29.

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

Natalia Lampon  1 , J Carlos Tutor
Affiliations

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

Natalia Lampon et al. Ups J Med Sci. 2012 Mar.

Abstract

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.

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Figures

Figure 1.
Figure 1.
Relationship between total (Css) and albumin normalized total (CssN) concentrations of valproic acid in epileptic patients of <65 (○) and ≥65 (•) years of age. The dashed lines correspond to the limits of the valproic acid therapeutic range (50–100 μg/mL).
See this image and copyright information in PMC

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