Notes & Sources

• Phenytoin is roughly 90% albumin-bound; only the free fraction is pharmacologically active. In hypoalbuminaemia a total level looks low while the free level may be therapeutic or even toxic.
• In significant renal impairment, uraemic toxins displace phenytoin from albumin, so the binding coefficient falls from 0.2 to 0.1. Selecting the renal option applies that change.
• Reference ranges used here: total 10-20 mcg/mL, free 1-2 mcg/mL. The estimated free level assumes a 10% free fraction.
• Where a free level can be measured directly, measure it. This correction is an estimate and performs poorly at the extremes of albumin.
• Valproate displaces phenytoin from albumin. With concurrent valproate this equation underestimates the free level, and a measured free concentration is strongly preferred.