Comparative Pharmacology
Head-to-head clinical analysis: DILANTIN versus DIVALPROEX SODIUM.
Peer-Reviewed Evidence
Head-to-head clinical analysis: DILANTIN versus DIVALPROEX SODIUM.
DILANTIN vs DIVALPROEX SODIUM
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 brain concentrations of gamma-aminobutyric acid (GABA), blocks voltage-gated sodium channels, and modulates 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.
10-15 mg/kg/day orally in divided doses; increase by 5-10 mg/kg/week; maximum 60 mg/kg/day. Extended-release: 25 mg/kg/day orally; increase by 15 mg/kg/day at weekly intervals; maximum 60 mg/kg/day.
None Documented
None Documented
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.
9-16 hours (terminal); shorter in children (6-9 hours) and longer in hepatic disease or elderly; clinical context: twice-daily dosing provides stable trough concentrations.
Primarily hepatic metabolism to inactive metabolites (p-hydroxyphenyltoin and glucuronide conjugate). Less than 5% excreted unchanged in urine. Fecal excretion minimal (<2%).
Renal: <3% unchanged; primarily hepatic metabolism (glucuronidation, beta-oxidation, cytochrome P450), metabolites eliminated renally; fecal: negligible.
Category C
Category D/X
Anticonvulsant
Anticonvulsant