Comparative Pharmacology
Head-to-head clinical analysis: PHENYTOIN versus ZONISADE.
Peer-Reviewed Evidence
Head-to-head clinical analysis: PHENYTOIN versus ZONISADE.
PHENYTOIN vs ZONISADE
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.
Zonisamide is a sulfonamide anticonvulsant. Its precise mechanism of action is unknown, but it is believed to inhibit voltage-sensitive sodium channels and reduce T-type calcium currents, thereby stabilizing neuronal membranes and suppressing neuronal hypersynchronization. It may also modulate GABA and glutamate neurotransmission.
Oral: 300-400 mg/day in 3-4 divided doses; IV: 15-20 mg/kg loading dose, then 300 mg/day maintenance.
100-200 mg orally every 8 hours; maximum 600 mg/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: 63-69 hours in adults; allows once-daily dosing; steady-state achieved in 14-21 days
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%.
Renal: approximately 62% (35% unchanged, 27% as glucuronide conjugate); fecal: 3%; biliary: negligible
Category D/X
Category C
Anticonvulsant
Anticonvulsant