Comparative Pharmacology
Head-to-head clinical analysis: PHENYTOIN SODIUM versus ZONISADE.
Peer-Reviewed Evidence
Head-to-head clinical analysis: PHENYTOIN SODIUM versus ZONISADE.
PHENYTOIN SODIUM vs ZONISADE
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
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. Prolongs inactivation of voltage-gated sodium channels, reducing 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.
Loading dose: 15-20 mg/kg IV (not to exceed 50 mg/min) or oral (1000-1500 mg total in divided doses). Maintenance: 300-400 mg/day PO in 1-2 divided doses or IV (100 mg every 6-8 hours).
100-200 mg orally every 8 hours; maximum 600 mg/day.
None Documented
None Documented
Mean terminal half-life 22 ± 9 hours (range 7–42 hours), dose-dependent and saturable due to Michaelis-Menten kinetics; half-life increases with higher serum concentrations. Steady state achieved after 7–10 days.
Terminal elimination half-life: 63-69 hours in adults; allows once-daily dosing; steady-state achieved in 14-21 days
Primarily hepatic metabolism (CYP2C9, CYP2C19); <5% excreted unchanged in urine. Metabolites (majority p-HPPA) are excreted renally as glucuronide conjugates. Fecal elimination negligible (<2%).
Renal: approximately 62% (35% unchanged, 27% as glucuronide conjugate); fecal: 3%; biliary: negligible
Category D/X
Category C
Anticonvulsant
Anticonvulsant