Unit Converter
Phenytoin

SI UNITS (recommended)

CONVENTIONAL UNITS

Synonyms

  • Phenytoin
  • Diphenylhydantoin
  • DPH
  • Dilantin (brand)
  • Sodium phenytoin
  • Anti-epileptic drug (AED)

Units of Measurement

  • µmol/L
  • mg/L
  • mg/dL
  • mg/100 mL
  • mg%
  • µg/mL

Molecular Weight

252.27 g/mol

Key Unit Conversions

Mass ↔ Molar

1 mg/L=3.96 µmol/L1\ \text{mg/L} = 3.96\ \text{µmol/L}1 mg/L=3.96 µmol/L 1 µmol/L=0.252 mg/L1\ \text{µmol/L} = 0.252\ \text{mg/L}1 µmol/L=0.252 mg/L

mg/dL ↔ mg/L

1 mg/dL=10 mg/L1\ \text{mg/dL} = 10\ \text{mg/L}1 mg/dL=10 mg/L

µg/mL

1 µg/mL=1 mg/L1\ \text{µg/mL} = 1\ \text{mg/L}1 µg/mL=1 mg/L

mg%

\text{mg%} = \text{mg/dL}

Description

Phenytoin is a hydantoin-class antiepileptic drug that stabilizes neuronal membranes by blocking voltage-gated sodium channels, preventing repetitive firing.

It has:

  • Non-linear (Michaelis–Menten) kinetics
  • Narrow therapeutic index
  • Very high protein binding (≈ 90%)
  • Significant drug–drug interactions
  • Long half-life (22 hours average)

Because of its pharmacokinetics, small dose changes can cause large serum level shifts, making therapeutic drug monitoring essential.

Physiological Role

None — phenytoin is a synthetic pharmacologic agent.

Clinical Significance

Therapeutic Uses

  • Generalized tonic–clonic seizures
  • Focal seizures
  • Status epilepticus (IV form)
  • Post-traumatic seizure prophylaxis
  • Certain arrhythmias (occasionally)

HIGH Phenytoin Levels (Toxicity)

Neurological

  • Nystagmus (early sign)
  • Ataxia
  • Slurred speech
  • Lethargy
  • Confusion
  • Diplopia
  • Coma (severe)

Cardiovascular (IV use)

  • Hypotension
  • Arrhythmias
  • Cardiac arrest with rapid infusion

Gastrointestinal

  • Nausea, vomiting

Chronic Toxicity

  • Gingival hyperplasia
  • Hirsutism
  • Osteopenia/osteoporosis
  • Folate deficiency
  • Peripheral neuropathy

Causes of high levels

  • Excess dose
  • Drug interactions (valproate displaces protein binding)
  • Liver disease
  • Hypoalbuminemia (↑ free fraction)
  • Kidney disease (↑ free fraction)

LOW Phenytoin Levels

  • Poor compliance
  • Under-dosing
  • CYP450 induction (carbamazepine, rifampicin)
  • Pregnancy (↑ clearance)
  • Nephrotic syndrome (↑ loss of protein-bound drug)

Low levels → seizure breakthrough.

Reference Intervals (Therapeutic Ranges)

Total Phenytoin

  • 10 – 20 mg/L
     (= 10–20 µg/mL)
    (= 39 – 79 µmol/L)

Free (Unbound) Phenytoin

  • 1 – 2 mg/L
     (= 1–2 µg/mL)
    (= 4 – 8 µmol/L)

Critical Toxic Level

  • > 30 mg/L → neurotoxicity likely
  • > 40 mg/L → severe toxicity

Status Epilepticus (IV loading)

Target: 15–20 mg/L after loading

Correcting Phenytoin Level in Hypoalbuminemia

(Sheiner–Tozer Equation)

Corrected Level=Measured phenytoin(0.2×Albumin)+0.1\text{Corrected Level} = \frac{\text{Measured phenytoin}} {(0.2 \times \text{Albumin}) + 0.1}Corrected Level=(0.2×Albumin)+0.1Measured phenytoin​

Use in:

  • CKD
  • Liver disease
  • ICU patients
  • Malnutrition

Diagnostic Uses

1. Therapeutic Drug Monitoring (Main Use)

Adjust dosing for:

  • Efficacy
  • Toxicity prevention

2. Suspected Toxicity

Evaluate nystagmus, ataxia, confusion.

3. Status Epilepticus Management

Monitor post-loading level.

4. Pregnancy Monitoring

Increased clearance → frequent dose adjustment required.

5. Drug Interaction Monitoring

Phenytoin is a potent CYP450 inducer affecting dozens of drugs.

Analytical Notes

  • Use trough sample (just before next dose)
  • Always interpret with albumin concentration
  • Free phenytoin measurement preferred in:
    • Pregnancy
    • Renal failure
    • Liver disease
    • Hypoalbuminemia
  • Hemolysis interferes minimally
  • LC–MS/MS and immunoassays used

Clinical Pearls

  • Non-linear kinetics → small increases in dose can cause huge level changes.
  • Therapeutic levels do not guarantee seizure control; clinical judgment essential.
  • Valproate dramatically increases free phenytoin, causing toxicity even at normal total levels.
  • Correct levels using Sheiner–Tozer equation when albumin is low.
  • Long-term use may cause bone disease → advise vitamin D & calcium supplementation.

Interesting Fact

Phenytoin was discovered in 1938 and remains widely used because of its effectiveness, despite its complex pharmacokinetics and side effect profile.

References

  1. Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Antiepileptic Drug Monitoring
  2. ACCP Pharmacokinetics - Phenytoin
  3. Mayo Clinic Laboratories - Phenytoin
  4. ARUP Consult - AED Monitoring
  5. MedlinePlus / NIH - Phenytoin Test

Last updated: January 27, 2026

Reviewed by : Medical Review Board

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