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Blood Test Tracker

Phenytoin (Free)

Measures the active, unbound part of phenytoin (Dilantin) in your blood. It is a better guide than the total level when albumin is low or in kidney or liver disease.

AI-verified against cited sources. Awaiting expert reviewLOINC 3969-3

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What it is

Most phenytoin in your blood is attached to a protein called albumin and can't act on the brain. The small part that isn't attached, the free or unbound part, is the active drug. This test measures only the free part. It is used when the total phenytoin level may not reflect how much active drug you have.

Why it matters

In some people less phenytoin sticks to protein, so a usual-looking total level can hide a high free level. That can happen with low albumin, kidney or liver disease, serious illness and pregnancy. In these situations, FDA labeling advises basing monitoring on the unbound fraction. A free level can also help when side effects or seizure control don't match the total level.

If it’s low

A low free level means less active phenytoin than the usual range. Some people are controlled at lower levels, so your prescriber looks at the number together with your seizures and side effects. It also helps to check the timing of your last dose and whether the form of phenytoin was recently changed.

Common causes

  • Missed or late doses
  • A recent dose reduction, or not yet at a steady level after a change
  • Medicines that speed up phenytoin's breakdown

What can help

  • Tell your prescriber if you have missed doses or have trouble taking the medicine as planned
  • Ask whether your total and free levels tell the same story

If it’s high

A high free level means more active phenytoin than the usual range, even if the total level looks usual. Side effects such as eye flicking, unsteady walking, slurred speech and drowsiness become more likely. The usual link between total and free levels (free is about a tenth of total) can shift when albumin is low or other medicines compete for binding.

Common causes

  • Low albumin, or kidney or liver disease, which leaves more phenytoin unbound
  • A recent dose increase
  • Medicines that slow phenytoin's breakdown, or that compete with it for albumin
  • Changes in protein binding during pregnancy

What can help

  • Ask your prescriber how this result fits with your total level and how you have been feeling
  • Tell your prescriber about every medicine and supplement you take
  • Ask whether your albumin, kidney and liver tests should be checked

Usual ranges

What labs print as the reference range, by who was tested. Ranges differ a little between labs, so the range on your own report is the one your result is judged against.

For adults: 1–2 mcg/mL. Source: Viatris Specialty (DailyMed), Frontiers in Pharmacology, Indian Journal of Critical Care Medicine, ARUP Laboratories. Labs treat above 2.9 mcg/mL as urgent.

What can affect your result

  • Albumin level, kidney disease, liver disease and critical illness
  • Pregnancy, which can change protein binding
  • Other medicines that compete with phenytoin for albumin or change its breakdown
  • Dose changes: a small increase can raise the level a lot
  • Timing of the draw relative to your dose
  • Recent fosphenytoin (Cerebyx), which can falsely raise some tests until it converts
  • After fosphenytoin (Cerebyx), wait until it has converted to phenytoin, about 2 hours after the end of an IV infusion or 4 hours after an IM injection. Before that, common immunoassays can read falsely high, while chromatographic methods stay accurate.
  • Low albumin, kidney or liver disease, serious illness and pregnancy change how much phenytoin is unbound. The free test is meant to account for this, but the total level may not match it.
  • Medicines that compete with phenytoin for albumin binding can raise the free level without changing the total much.
  • Phenytoin is broken down by a saturable process, so a small dose change can produce a large change in level.

Usually a trough, drawn just before the next scheduled dose once the level has reached a steady state. At least 7 to 10 days (5 to 7 half-lives) to reach a steady level after starting or changing the dose. The average half-life is about 22 hours, with a range of 7 to 42 hours.

When to talk to a clinician

Contact your prescriber promptly for new unsteady walking, eye flicking, slurred speech, marked drowsiness or confusion, or if seizures become more frequent. A new skin rash, fever or swollen glands while taking phenytoin also needs prompt attention. Talk with your prescriber before changing or stopping phenytoin. If someone may have taken too much, can't be woken, or has trouble breathing, call 911 or your local emergency number.

Questions you could ask

  • Should my phenytoin be monitored with free or total levels?
  • What free level are you aiming for in my case?
  • Is my albumin or kidney function affecting my free level?
  • Could another medicine be pushing phenytoin off albumin?
  • Could missed doses or a recent change explain this result?

Questions people ask

When is a free phenytoin level better than a total level?

When less phenytoin than usual is attached to albumin, such as with low albumin, kidney or liver disease, serious illness or pregnancy. In those cases the total level can be misleading, while the free level shows the active part directly.

Why is my free level so much lower than my total level?

Most phenytoin sticks to albumin, and usually only about a tenth is free. That is why a total level of 10 to 20 mcg/mL goes with a free level of about 1 to 2 mcg/mL.

How do I convert mcg/mL to µmol/L?

Multiply mcg/mL by 3.96, so 1 mcg/mL is about 4 µmol/L and 2 mcg/mL is about 8 µmol/L. To go the other way, multiply µmol/L by 0.2523.

Show the science and sources

Units

  • 1 mcg/mL = 1 mcg/mL
  • 1 mcg/mL = 1 mg/L
  • 1 mcg/mL = 3.964 µmol/L

Open the Free Phenytoin unit converter

For clinicians and researchers

Free phenytoin is measured in the protein-free ultrafiltrate of serum or plasma. At usual albumin levels about 90% of phenytoin is protein-bound, so the unbound fraction is roughly a tenth of the total, which is why FDA labeling pairs a total range of 10 to 20 mcg/mL with an unbound range of 1 to 2 mcg/mL. The unbound fraction rises with hypoalbuminemia, uremia, hepatic disease, pregnancy and displacing drugs, and because hepatic clearance is saturable, small changes in free concentration can follow dose changes disproportionately. ARUP reports the percent free as 8 to 14%. Equations that correct a total level for albumin (Sheiner-Tozer) can mislead in critically ill patients with low albumin; a 2022 study found direct measurement of free phenytoin to be the better approach. Immunoassays cross-react with fosphenytoin until conversion is complete (about 2 hours after IV infusion, 4 hours after IM), so chromatographic methods are preferred early on. A 2026 survey of 411 US hospitals found that about 39% list a free-phenytoin critical limit, with a median of 2.9 mcg/mL (range 1.8 to 4). 1 mcg/mL equals 3.964 µmol/L (molecular weight 252.27). Total phenytoin is a separate marker.

LOINC 3969-3 (primary), 32109-1, 74983-8. Specimen: serum-or-plasma.

Sources

  1. Drug Critical Limits for Urgent Physician Notification, Clinical Pharmacology & Therapeutics (2026)
  2. Dilantin (extended phenytoin sodium) capsules: prescribing information, Viatris Specialty (DailyMed) (2023)
  3. Cerebyx (fosphenytoin sodium) injection: prescribing information, Pfizer (DailyMed) (2025)
  4. Estimation of Free Phenytoin Concentration in Critically Ill Patients with Hypoalbuminemia: Direct-measurement vs Traditional Equations, Indian Journal of Critical Care Medicine (2022)
  5. Phenytoin, Free and Total (test 0090141), ARUP Laboratories
  6. Effect of hypoalbuminemia on drug pharmacokinetics, Frontiers in Pharmacology (2025)
  7. Phenytoin (PubChem CID 1775), PubChem, National Library of Medicine

AI-verified against cited sources. Awaiting expert review. Last reviewed 2026-10-03. How we build and check these pages.

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