# Slows inward Na and Ca ion flux during depolarisation and delays outward K flux.
◦ Stabilises the inactive state of V-gated Na channels limiting repetitive generation of APs.
▪ Limits spread of seizure
◦ Reduce glutamate release and thus attenuating Ca entry
# Enhance action of GABA

1. Partial inhibition of N-type Ca2+ currents and reduced release of Ca2+ from intra-neuronal stores causing
reduced intra-neuronal Ca.
2. Inhibition of synaptic vesicle protein 2A (SV2A) involved in vesicle fusion and neurotransmitter exocytosis
# → membrane hyperpolarisation → ↓NT release.

IV, PO – variable 30-75%

IV, PO Rapidly abs- BA 100%.

90% protein bound

<10% protein bound

Vd – 0.6-0.7 L/kg

# Hepatic to parahydroxyphenyl (inactive)
◦ hydroxylation by CYP450 2C9
▪ Metabolism effected by inducers or inhibitors of CYP450 2C9
◦ induces its own CYP450
# Mixed 1st and zero order kinetics as process is saturable
◦ 1st order at plasma [] 10 µg/mL ▪ t1/2 dose dependent

# Enzymatic hydrolysis (24%) in a large number of tissues including whole blood but not plasma.

< 3% unchanged in urine

# 95% excreted in the urine
# 65% unchanged

T1/2 7hrs

# Hydantoin derivative
# Precipitates at pH < 7
◦ → variable oral absorption
◦ → IM contraindicated

# Pyrrolidine
# Highly lipid soluble

Anticonvulsant

Anticonvulsant

Anticonvulsant and antiarrhythmic (V-W class 1b)
Epilepsy
Trigeminal neuralgia
TCA toxicity
Digoxin-induced arrhythmias

Epilepsy in the case of partial seizures
Adjunctive therapy for partial, myoclonic and tonic-clonic seizures

Level 2

Level 3

Capsules, Syrups, Injections
# Doses 15-20 mg/kg IV loading  maintenance (plasma levels
required aim 10-20µg/mL)
# Rapidly achieves peak (<20mins after loading)
# Duration 30mins-1hr but highly variable

# Steady state after two days of a twice
daily administration schedule.
# Dose: PO/IV 1000 mg daily given as
500 mg 2 times a day