NAPLEX PK reminder — never interpret a phenytoin level without looking at the albumin
This one shows up constantly and the wrong answer is the intuitive one. Setup: total phenytoin 8 mcg/mL (range 10–20), albumin 2.0 g/dL, normal renal function. Looks subtherapeutic, so you'd increase the dose, right?
No. Phenytoin is ~90% albumin-bound and only free drug is active. Low albumin → higher free fraction → the total level you measure understates the real picture. Correct it with Sheiner-Tozer:
corrected = measured ÷ [(0.2 × albumin) + 0.1]
= 8 ÷ [(0.2 × 2.0) + 0.1] = 8 ÷ 0.5 = 16 mcg/mL → therapeutic, don't touch the dose.
Things they build distractors around:
- Use 0.1 instead of 0.2 for the albumin coefficient only in ESRD/severe uremia. Applying it to normal renal function here gives 26.7 and a wrong "toxic" call.
- Nonlinear (Michaelis-Menten) kinetics is why the wrong move is genuinely dangerous — small dose increases can produce outsized concentration jumps. Toxicity landmarks: nystagmus >20, ataxia >30, mental status changes >40.
- Valproic acid displaces phenytoin from albumin and isn't accounted for by Sheiner-Tozer at all.
Worth knowing for practice (and occasionally tested): if a free phenytoin level is available, use it — it beats any correction equation, especially in ICU patients where Sheiner-Tozer has documented accuracy problems.
Anyone else keeping a list of "labs you can't read at face value"? Phenytoin/albumin and calcium/albumin are the two that got me most.
Posted Jul 23, 2026, 5:14 AM UTC