Comparative Pharmacology
Head-to-head clinical analysis: PHENYTOIN versus VALPROATE SODIUM.
Peer-Reviewed Evidence
Head-to-head clinical analysis: PHENYTOIN versus VALPROATE SODIUM.
PHENYTOIN vs VALPROATE SODIUM
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
Phenytoin is a hydantoin anticonvulsant that 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 use-dependently blocks voltage-gated sodium channels, prolonging their inactivation phase and reducing high-frequency repetitive firing of action potentials.
Increases GABA levels by inhibiting GABA transaminase and blocking voltage-gated sodium channels; also modulates T-type calcium channels.
Oral: 300-400 mg/day in 3-4 divided doses; IV: 15-20 mg/kg loading dose, then 300 mg/day maintenance.
10-15 mg/kg/day orally or intravenously in 2-3 divided doses; increase by 5-10 mg/kg/day weekly to therapeutic range of 50-100 mcg/mL. Maximum dose 60 mg/kg/day.
None Documented
None Documented
Clinical Note
moderatePhenytoin + Digoxin
"The metabolism of Digoxin can be increased when combined with Phenytoin."
Clinical Note
moderateFosphenytoin + Digoxin
"The metabolism of Digoxin can be increased when combined with Fosphenytoin."
Clinical Note
moderatePhenytoin + Digitoxin
"The metabolism of Digitoxin can be increased when combined with Phenytoin."
Clinical Note
moderateFosphenytoin + Digitoxin
"The metabolism of Digitoxin can be increased when combined with Fosphenytoin."
Average terminal half-life 22 hours (range 7–42 hours) in adults; dose-dependent due to saturation of metabolism at therapeutic concentrations (10–20 mg/L). Half-life increases with higher doses.
Terminal elimination half-life is 9–16 hours in adults; may be shorter in children (5–12 hours) and prolonged in hepatic impairment or elderly (up to 18 hours). Neonatal half-life: 10–67 hours. Clinically, twice-daily dosing is typical.
Primarily hepatic metabolism (>95%); less than 5% excreted unchanged in urine. Renal excretion of metabolites (glucuronides) accounts for ~80% of elimination; biliary/fecal excretion of metabolites ~20%.
Primarily renal (90% as glucuronide conjugates, 3-oxo derivative, and other metabolites; <3% unchanged). Biliary/fecal excretion accounts for <10%.
Category D/X
Category C
Anticonvulsant
Anticonvulsant