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Phenytoin Protein Binding Hypoalbuminaemia — ESENeph MCQ

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HardElectrolyte DisordersPhenytoin Protein Binding HypoalbuminaemiaESENeph

A 40-year-old man with nephrotic syndrome has a serum albumin of 18 g/L. His pharmacist notes that his Phenytoin level is therapeutic at 65 umol/L (target 40-80). However, the patient is having seizures. What pharmacokinetic issue explains this?

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Correct answer: B — In hypoalbuminaemia as the preferred next step

Phenytoin is >90% protein-bound (primarily to albumin). In hypoalbuminaemia, the bound fraction decreases and the free (pharmacologically active) fraction increases. Total Phenytoin level may appear therapeutic while the free level is toxic. The Sheiner-Tozer equation adjusts total Phenytoin for low albumin: Adjusted level = Measured level / (0.2 x albumin/44 + 0.1) for non-renal patients, or / (0.1 x albumin/44 + 0.1) for CKD. Alternatively, free Phenytoin level should be measured directly. This pharmacokinetic principle applies to all highly protein-bound drugs in nephrotic syndrome.

Reference: https://guidelines.ukkidney.org