<p>Protein binding is linear at low concentrations with a free fraction of approximately 10% at 40 mcg/mL but becomes non-linear at higher concentrations with a free fraction of 18.5% at 135 mcg/mL.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Official drug label" href="#label-reference">Label</a></sup> This may be due to binding at separate high and low-affinity sites on albumin proteins.<sup class="text-reference-group"><a class="reference-popover-link" data-content="Zaccara G, Messori A, Moroni F: Clinical pharmacokinetics of valproic acid--1988. Clin Pharmacokinet. 1988 Dec;15(6):367-89. doi: 10.2165/00003088-198815060-00002. (PubMed ID 3149565)" href="#reference-A178066">27</a></sup> Binding is expected to decrease in the elderly and patients with hepatic dysfunction.</p>