Valproate Unit Converter
Valproate Unit Converter
Convert valproate between µg/mL, mg/L and µmol/L, and see why saturable protein binding means the total level understates exposure — and when a free valproate level is the right test.
Valproate converter
Mass ⇄ molarValproic acid 72 µg/mL, trough sample
Formula and conversion factor
µg/mL = µmol/L ÷ 6.93433
- 6.93
- derived from the molecular mass of valproic acid, 144.21 Da (1000 ÷ 144.21)
- mg/L
- numerically identical to µg/mL
- total vs free
- the routine assay measures total drug; binding saturates within the therapeutic range, so the free — active — fraction rises faster than the total
Worked example
Valproic acid 72 µg/mL, trough sample
72 × 6.93433 = 499 µmol/L
= 72 mg/L
Within the 50 – 100 µg/mL trough range
Conventional and SI thresholds
| µg/mL (= mg/L) | µmol/L | |
|---|---|---|
| Trough target, epilepsy | 50 – 100 | 347 – 693 |
| Below target | < 50 | < 347 |
| Above target — check free level | > 100 | > 693 |
When to send a free valproate level instead of a total
| Situation | Why the total misleads |
|---|---|
| Hypoalbuminaemia | Less binding protein, so a normal total corresponds to a higher free fraction |
| Renal failure | Uraemic solutes displace valproate from albumin |
| High total level | Binding is already saturated, so the free fraction rises disproportionately |
| Toxicity with a therapeutic total | The free concentration may be well above the total-based range |
Total, free, and the trap of a normal number
Valproate is reported in µg/mL or mg/L — the two are numerically identical — and in µmol/L in SI-reporting laboratories. The molar factor is 6.93, derived from valproic acid’s molecular mass of 144.21, so a total valproate of 72 µg/mL is 499 µmol/L. The two scales are far enough apart that a µmol/L result mistakenly read as µg/mL looks like gross toxicity.
Sample at trough, immediately before a dose. Valproate concentrations swing substantially across a dosing interval, particularly with immediate-release preparations, and a level drawn an hour or two after a dose can be considerably higher than the trough. A level without a recorded time relative to the dose is not interpretable and should be repeated rather than acted on, because the same number means different things at different points in the interval.
The most important pharmacokinetic feature is protein binding. Valproate is highly bound to albumin, and that binding saturates within the therapeutic range, so as the dose rises the total concentration rises less than proportionally while the unbound — pharmacologically active — fraction rises faster. The routine assay measures total drug and therefore understates exposure at the top of the range. In hypoalbuminaemia, in renal failure, and where a high total level accompanies unexplained toxicity, a free valproate level is the right test.
Hyperammonaemic encephalopathy is the trap. It can occur at entirely therapeutic total concentrations, presents as drowsiness, confusion or a deterioration in seizure control rather than as classical overdose, and is not excluded by a normal level — the ammonia has to be measured separately. Valproate is also hepatotoxic and highly teratogenic, and must not be used in pregnancy or in a person able to become pregnant except under the specific safeguards required by national regulators.
Frequently asked questions
How do I convert valproate from µg/mL to µmol/L?
Multiply by 6.93, derived from valproic acid’s molecular mass of 144.21 Da. A level of 72 µg/mL is 499 µmol/L. Note that µg/mL and mg/L are the same number.
When should a valproate level be taken?
At trough, immediately before a dose. Concentrations swing widely across the dosing interval, so a mid-interval sample reads high. A level with no recorded timing relative to the dose cannot be interpreted and should be repeated.
Why does the total valproate level understate exposure?
Valproate is highly protein-bound and that binding saturates within the therapeutic range. As the dose rises the total rises less than proportionally while the free, active fraction rises faster, so the total assay increasingly understates the drug that matters.
When should I request a free valproate level?
In hypoalbuminaemia, in renal failure, and when a high total level accompanies unexplained toxicity. In each case the fraction of drug that is unbound is higher than the total level implies.
Does a normal valproate level exclude hyperammonaemic encephalopathy?
No. Hyperammonaemic encephalopathy occurs at entirely therapeutic concentrations and is not excluded by a normal level. If a patient on valproate becomes drowsy or confused, measure the ammonia rather than relying on the drug level.
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References
- Patsalos PN, Berry DJ, Bourgeois BFD, et al. Antiepileptic drugs — best practice guidelines for therapeutic drug monitoring: ILAE position paper. Epilepsia. 2008;49(7):1239–1276.
- Zaccara G, Messori A, Moroni F. Clinical pharmacokinetics of valproic acid — 1988. Clin Pharmacokinet. 1988;15(6):367–389.
- Joint Formulary Committee. British National Formulary. London: BMJ Group and Pharmaceutical Press.