Valproic Acid / Divalproex (Depakote)
Branched-chain fatty acid anticonvulsant and mood stabilizer with multiple mechanisms: increases GABA via inhibition of GABA transaminase, blocks voltage-gated sodium channels, and inhibits histone deacetylase. First-line for generalized epilepsy, bipolar mania, and migraine prophylaxis. Highly protein-bound (90-95%) with nonlinear kinetics at saturation. Narrow therapeutic index requiring serum monitoring (50-125 mcg/mL). Teratogenic (Category X), neural tube defects. Hepatotoxicity risk especially in children <2 years.
Projected serum levels — 500 mg, twice daily
Maintenance schedule: 500 mg twice daily (oral).
Loading schedule: 1.1k mg on day 1, then 500 mg twice daily — reaching therapeutic levels sooner.
Modeled steady state after ~2 days: peak ≈ 965 mg, trough ≈ 569 mg body load. Population-based estimate over 15 days for a 500 mg dose at a 70 kg reference body mass — the interactive app scales curves to your doses, timing, and body mass.
Key facts
- Category
- Anticonvulsant
- Route modeled
- Oral
- Model confidence
- inferred
- Half-life
- 13 h
- Common dose
- 500 mg
- Suggested maximum
- 3k mg/day
- Reference dose range
- 250–3k mg (single dose)
- Suggested cadence
- twice daily
- Validated against
- 500 mg oral — Cmax 70 mg/L at 2 h
Documented interactions
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danger
Candesartan + Valproic Acid / Divalproex (Depakote)
Valproic Acid / Divalproex (Depakote) reversible_inhibitor of CYP2C9 predicted to change Candesartan AUC by ~3.33x
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danger
Celecoxib (Celebrex) + Valproic Acid / Divalproex (Depakote)
Valproic Acid / Divalproex (Depakote) reversible_inhibitor of CYP2C9 predicted to change Celecoxib (Celebrex) AUC by ~2.97x
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danger
Cyclosporine (Sandimmune/Neoral) + Valproic Acid / Divalproex (Depakote)
Valproic Acid / Divalproex (Depakote) may displace Cyclosporine (Sandimmune/Neoral) from plasma protein binding sites, transiently raising free drug concentration. This drug has a narrow therapeutic…
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danger
Glipizide (Glucotrol) + Valproic Acid / Divalproex (Depakote)
Valproic Acid / Divalproex (Depakote) reversible_inhibitor of CYP2C9 predicted to change Glipizide (Glucotrol) AUC by ~2.47x
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danger
Levothyroxine (Synthroid) + Valproic Acid / Divalproex (Depakote)
Valproic Acid / Divalproex (Depakote) may displace Levothyroxine (Synthroid) from plasma protein binding sites, transiently raising free drug concentration. This drug has a narrow therapeutic index;…
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danger
Meloxicam (Mobic) + Valproic Acid / Divalproex (Depakote)
Valproic Acid / Divalproex (Depakote) reversible_inhibitor of CYP2C9 predicted to change Meloxicam (Mobic) AUC by ~2.20x
Serum checks 232 modeled interaction pairings for valproic acid / divalproex (depakote) across your whole stack — absorption conflicts, enzyme inhibition, and nutrient depletion included.
Research behind this entry
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Divalproex sodium versus placebo for acute treatment of mania in bipolar disorder (Bowden 1994)
Landmark RCT establishing divalproex as effective for acute mania, with 48% response rate versus 25% placebo, leading to FDA approval for bipolar disorder treatment.
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Valproic acid for prophylaxis of migraine: a systematic review and meta-analysis
Cochrane review of 10 RCTs confirming valproate reduces migraine frequency by approximately 50% compared to placebo, with efficacy comparable to topiramate and propranolol.
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Clinical pharmacokinetics of valproic acid
Definitive PK review establishing valproate half-life of 9-16 hours (shorter with enzyme inducers), 90-95% protein binding with saturable kinetics, hepatic metabolism, and the importance of free-fraction monitoring.
3 published studies referenced in the app, each with a plain-language summary.