Sodium Valproate and Valproate: Chemical Equivalence
Sodium valproate, valproic acid, and divalproex sodium are different formulations that all deliver the same active substance—the valproate ion—and are clinically equivalent in terms of therapeutic effects and safety profiles. 1, 2, 3
Chemical Relationship
- Valproic acid dissociates to the valproate ion in the gastrointestinal tract, which is the active therapeutic substance regardless of which formulation is administered 2
- Sodium valproate is the sodium salt of valproic acid, while divalproex sodium is an equimolar combination (1:1 ratio) of sodium valproate and valproic acid 3, 4
- All oral formulations are almost completely bioavailable (approximately 100%), though they differ in dissolution characteristics and absorption rates 5, 3
Clinical Equivalence
- Equivalent oral doses of divalproex sodium products and valproic acid capsules deliver equivalent quantities of valproate ion systemically 2
- Eight comparative efficacy studies found no differences between valproic acid and other valproate formulations in treating epilepsy or mood disorders 1, 3
- The therapeutic range for epilepsy is 50-100 mcg/mL of total valproate, regardless of formulation, with total daily systemic bioavailability being the primary determinant of seizure control 1, 2
Shared Safety Profile
- The American Academy of Neurology and other medical societies acknowledge that all valproate formulations carry identical risks for serious adverse effects, including hepatotoxicity, thrombocytopenia, teratogenicity, and reproductive endocrine disorders 1
- All formulations are absolutely contraindicated in women of childbearing potential unless there is no suitable alternative and a pregnancy prevention program is implemented 6, 2
- Women on any valproate formulation monotherapy experience high rates of reproductive endocrine disorders: 45% with menstrual irregularities, 60% with polycystic ovaries, and 30% with elevated testosterone 7, 1
Practical Considerations
- While absorption rates may vary between formulations (affecting Tmax and Cmax), these differences are of minor clinical importance under steady-state conditions achieved in chronic epilepsy treatment 2
- Substitution among various divalproex sodium and valproic acid formulations should cause no clinical problems in epilepsy management, though close monitoring of clinical status and valproate plasma concentrations is recommended with any formulation changes 2
- The terms "sodium valproate" and "valproate" are often used interchangeably in clinical practice and medical literature, as they refer to the same therapeutic entity 8, 1