Showing posts from May, 2023

Unbound and Uncharted - Therapeutic Drug Monitoring of Free Valproic Acid in ICU Patients

  I'm sorry to break this to you, but your ICU patient’s valproate (VPA) level may be lying to you. Hidden within the total valproate concentration you checked is the concentration that matters – the free concentration, which is pharmacologically active and primarily responsible for the CNS exposure to VPA 1,2 – but without peeking under the hood and directly measuring that free concentration, it is nearly impossible to predict exactly how much VPA your patient is exposed to. Because of this, dose adjustments made based on total concentrations have the risk of widely missing the mark. While altered protein binding with valproic acid is a well-known phenomenon especially in the setting of drug interactions like co-therapy with phenytoin, the extent to which protein binding can be altered in ICU patients is criminally underrecognized. Here we'll talk a bit about how VPA’s pharmacokinetics are unique, what factors influence its binding to albumin, why those factors matter