Macromate Mechanism of Action

Pharmacologic category: Anticonvulsant. ATC code: N03AX11.
Pharmacology: Pharmacodynamics: Mechanism of action: Topiramate is a sulfamate-substituted monosaccharide. The precise mechanisms by which topiramate exerts its anticonvulsant and migraine prophylaxis effects are unknown; however, data from electrophysiologic and biochemical studies have revealed 4 properties of topiramate e.g., blocks voltage-dependent sodium channels, augments the activity of the neurotransmitter γ-aminobutyrate at GABA_A acitivity, antagonizes the AMPA/kainate subtype of the glutamate receptor and weakly inhibits carbonic anhydrase.
Pharmacokinetics: Absorption: Topiramate is readily absorbed after oral dose, with peak plasma concentrations occurring after about 2 hours. Bioavailability is not affected by the affected food.
Distribution: Protein binding is about 9 to 17%. The volume of distribution (Vd) is 0.6 to 0.8 L/kg and Vd in women is about half that in men.
Metabolism: In the healthy subjects topiramate is not extensively metabolized in liver via hydroxylation, hydrolysis and glucuronidation; six minor metabolites have been identified, none of which constitutes more than 5% of an administered dose. However, up to 50% of a dose may undergo metabolism in the liver in patients also receiving enzyme inducing drugs.
Excretion: Topiramate is eliminated chiefly in urine, as unchanged drug and metabolites (Approximately 70%); mean plasma elimination half-life is about 21 hours. Steady-state concentrations occur after about 4 to 8 days in patients with normal renal function.