Phenytoin Unit Converter
Phenytoin Unit Converter
Convert phenytoin between µg/mL, mg/L and µmol/L, with the 40–79 µmol/L guide range, the saturable kinetics that make small dose changes dangerous, and why the total level misleads when albumin is low.
Phenytoin converter
Mass ⇄ molarPhenytoin 12.1 µg/mL, total, trough sample at steady state
Formula and conversion factors
µg/mL = µmol/L ÷ 3.96401
mg/L = µg/mL
- 3.96401
- derived from the molecular mass of phenytoin, 252.27 Da: 1 µg/mL is 0.001 g/L, and 0.001 ÷ 252.27 mol/L is 3.96401 µmol/L
- µg/mL = mg/L
- a microgram per millilitre and a milligram per litre are the same concentration, so no arithmetic is involved between them
- total against free
- this converts the total level. Roughly 90 per cent of phenytoin is bound to albumin, and it is the free 10 per cent that acts; the guide range for free phenytoin is about 1–2 mg/L, or 4–8 µmol/L
- zero-order kinetics
- metabolism saturates within the therapeutic range, so level does not rise in proportion to dose — a 10 per cent dose increase can raise the level far more
Worked example
Phenytoin 12.1 µg/mL, total, trough sample at steady state
12.1 µg/mL = 12.1 mg/L — the two units are identical
12.1 × 3.96401 = 47.96, so 48 µmol/L
Within the usual guide range of 40–79 µmol/L (10–20 µg/mL)
If this patient's albumin were 20 g/L (2.0 g/dL), the Sheiner-Tozer corrected total would be 24.2 µg/mL, about 96 µmol/L — well above the range despite the measured value sitting inside it
Thresholds across the units
| µg/mL (= mg/L) | µmol/L | |
|---|---|---|
| Usual guide range, total phenytoin | 10 – 20 | 40 – 79 |
| Usual guide range, free phenytoin | 1 – 2 | 4 – 8 |
| Nystagmus commonly appears above | 20 | 79 |
| Ataxia commonly appears above | 30 | 119 |
| Lethargy and confusion commonly appear above | 40 | 159 |
| Free fraction in a healthy adult | about 10% of total | about 10% of total |
When the total level misleads
| Situation | Effect on the total level | What to do |
|---|---|---|
| Hypoalbuminaemia | Falsely low relative to the free level — less protein to bind to | Apply the Sheiner-Tozer correction, or measure free phenytoin |
| Renal failure (eGFR under about 20) | Falsely low: uraemic toxins displace phenytoin from albumin | Use the renal-failure form of the correction, or measure free phenytoin |
| Valproate co-prescription | Falsely low: valproate displaces phenytoin from albumin and also inhibits its metabolism | Measure free phenytoin; the correction formulae do not handle displacement by another drug |
| Pregnancy, critical illness, nephrotic syndrome | Falsely low, through reduced albumin | Measure free phenytoin where the decision matters |
| Sample taken before steady state (5–14 days) | Underestimates the eventual level | Wait, then re-sample |
| Sample taken soon after a dose | Overestimates the trough | Take troughs immediately before the next dose |
Two reasons the number cannot be taken at face value
Phenytoin is reported in µg/mL or the numerically identical mg/L, and in µmol/L where SI units are used. The factor comes from the molecular mass of phenytoin, 252.27 daltons: one µg/mL is 3.96401 µmol/L, so the familiar 10 to 20 µg/mL guide range is 40 to 79 µmol/L. That range is a guide and not a target. Plenty of patients are seizure-free below it and some tolerate levels above it without symptoms, and a dose should never be adjusted to move a number in a patient whose seizures are controlled and who feels well.
The first reason for caution is kinetic. Phenytoin is metabolised by an enzyme system that saturates within the therapeutic range, so elimination is zero-order rather than first-order at clinically relevant concentrations. The practical consequence is that the level does not rise in proportion to the dose: an increase of 100 mg a day in a patient already near the top of the range can double or treble the concentration, and the apparent half-life lengthens as the level rises, so the excess clears slowly. Dose increases near the range are therefore made in steps of 25 to 50 mg, with a repeat level once a new steady state has been reached — five to fourteen days later.
The second reason is protein binding. Roughly 90 per cent of phenytoin circulates bound to albumin, and only the free 10 per cent crosses into the brain and does the work. When albumin falls, in nephrotic syndrome, liver disease, pregnancy or critical illness, or when uraemic toxins displace the drug in renal failure, the free fraction rises while the total falls. A patient can then be clinically toxic with a total level the report describes as therapeutic. Valproate does the same thing by displacement and compounds it by inhibiting metabolism.
Two responses are available. A measured free phenytoin, with its own guide range of about 1 to 2 mg/L or 4 to 8 µmol/L, answers the question directly but is not offered by every laboratory. Where it is not, the Sheiner-Tozer equation estimates what the total would have been at a normal albumin, with a separate form for renal failure; both are on this site. Neither replaces looking at the patient — nystagmus, ataxia and slurred speech are the findings that matter, and the level is there to explain them.
Frequently asked questions
How do I convert phenytoin from µg/mL to µmol/L?
Multiply by 3.96401, derived from the molecular mass of phenytoin, 252.27 daltons. A level of 10 µg/mL is 40 µmol/L and 20 µg/mL is 79 µmol/L, which is where the familiar 40–79 µmol/L guide range comes from. µg/mL and mg/L are the same number.
What is the therapeutic range for phenytoin?
Conventionally 10 to 20 µg/mL, or 40 to 79 µmol/L, for total phenytoin in a trough sample at steady state. It is a guide rather than a target: some patients are controlled below it and some tolerate levels above it, and the clinical picture takes precedence over the number.
Why does a small dose increase raise the phenytoin level so much?
Because phenytoin metabolism saturates within the therapeutic range, making elimination zero-order rather than first-order. Once the enzyme system is saturated the level rises steeply and disproportionately, so increases near the range are made in 25 to 50 mg steps with a repeat level after a new steady state.
Why can a normal phenytoin level still be toxic?
About 90 per cent of phenytoin is bound to albumin and only the free fraction is active. In hypoalbuminaemia, renal failure, pregnancy or critical illness the free fraction rises while the measured total falls, so a total level inside the range can accompany a free level well above it.
Should I use total or free phenytoin?
Total phenytoin is adequate in a patient with normal albumin and normal renal function. Where albumin is low, renal function is poor, valproate is co-prescribed, or the clinical picture and the level disagree, measure free phenytoin — or apply the Sheiner-Tozer correction if the free assay is unavailable.
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References
- Patsalos PN, Berry DJ, Bourgeois BFD, et al. Antiepileptic drugs — best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia. 2008;49(7):1239–1276.
- Sheiner LB, Tozer TN. Clinical pharmacokinetics: the use of plasma concentrations of drugs. In: Melmon KL, Morrelli HF, eds. Clinical Pharmacology: Basic Principles in Therapeutics. 2nd ed. New York: Macmillan; 1978:71–109.
- Winter ME. Basic Clinical Pharmacokinetics. 5th ed. Baltimore: Lippincott Williams & Wilkins; 2010.