Comparative Pharmacology
Head-to-head clinical analysis: DILANTIN versus VALPROIC ACID.
Peer-Reviewed Evidence
Head-to-head clinical analysis: DILANTIN versus VALPROIC ACID.
DILANTIN vs VALPROIC ACID
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
Phenytoin stabilizes neuronal membranes and decreases seizure activity by increasing efflux or decreasing influx of sodium ions across cell membranes in the motor cortex during generation of nerve impulses. It acts by blocking voltage-dependent sodium channels, thereby inhibiting the spread of seizure activity.
Increases GABA concentration in the brain by inhibiting GABA transaminase and succinic semialdehyde dehydrogenase; also blocks voltage-gated sodium channels and T-type calcium channels.
300–400 mg/day orally in 2–3 divided doses; IV loading dose 15–20 mg/kg at max 50 mg/min, then 300 mg/day IV divided 2–3 times daily.
Initial: 10-15 mg/kg/day orally (divided 2-3 times), increase by 5-10 mg/kg/week; maintenance: 30-60 mg/kg/day. IV infusion: same oral dose, rate ≤20 mg/min.
None Documented
None Documented
Clinical Note
moderateValproic acid + Fluticasone propionate
"The risk or severity of adverse effects can be increased when Valproic acid is combined with Fluticasone propionate."
Clinical Note
moderateValproic acid + Sulfisoxazole
"The metabolism of Sulfisoxazole can be decreased when combined with Valproic acid."
Clinical Note
moderateValproic acid + Cyclosporine
"The metabolism of Cyclosporine can be decreased when combined with Valproic acid."
Clinical Note
moderateValproic acid + Fluconazole
Average 22 hours (range 7-42 hours) in adults. Dose-dependent; increases with higher concentrations due to saturable metabolism. In neonates: 10-15 hours. In chronic use, half-life may increase.
Terminal elimination half-life is 9–16 hours in adults; shorter in children (6–9 hours) and longer in neonates (20–30 hours), elderly, or hepatic impairment (up to 18 hours).
Primarily hepatic metabolism to inactive metabolites (p-hydroxyphenyltoin and glucuronide conjugate). Less than 5% excreted unchanged in urine. Fecal excretion minimal (<2%).
Primarily hepatic metabolism (>95%), with less than 3% excreted unchanged in urine. Minor fecal excretion (~5%).
Category C
Category D/X
Anticonvulsant
Anticonvulsant
"The metabolism of Fluconazole can be decreased when combined with Valproic acid."