NAPLEX — National Pharmacist Licensure Examination

Phenytoin is approximately 90% protein-bound (primarily to albumin) in patients with normal albumin (4.0 g/dL). In hypoalbuminemia, fewer binding sites are available, increasing the free (pharmacologically active) fraction. The measured total level appears therapeutic (12 mcg/mL) but underestimates the actual drug effect. The Sheiner-Tozer equation adjusts the total phenytoin level: Adjusted concentration = Measured concentration / (0.2 × albumin + 0.1). With albumin 2.0: 12 / (0.2 × 2.0 + 0.1) = 12 / 0.5 = 24 mcg/mL. This adjusted level of 24 mcg/mL exceeds the therapeutic range (10-20), indicating potential toxicity despite the apparently therapeutic measured level. Clinical signs of phenytoin toxicity follow a dose-dependent progression: nystagmus (>20), ataxia (>30), lethargy (>40), and coma (>50). Free phenytoin level measurement (therapeutic 1-2 mcg/mL) directly assesses the active fraction and avoids the need for correction equations. Always adjust phenytoin levels in hypoalbuminemia, renal failure (uremia displaces binding), and hepatic disease.