Pitomate Mechanism of Action

Pharmacology: Pharmacodynamics: Topiramate, a sulfamate-substituted derivative of the monosaccharide D-fructose, is an anticonvulsant agent that also is used for prophylaxis of migraine headache. Topiramate blocks voltage-dependent sodium channels; augments the activity of γ-aminobutyric acid (GABA) at some subtypes of the GABA-A receptor; antagonizes the AMPA/kainate subtype of the glutamate receptor; and inhibits carbonic anhydrase (particularly the CA-II and CA-IV isoenzymes).
Pharmacokinetics: Absorption: Topiramate is rapidly absorbed with peak plasma concentrations occurring about 1 to 4 hours in adults, 1 to 2.8 hours in children 4 to 17 years and 3.7 hours in children 9 months to less than 4 years, following an oral dose. The bioavailability of Topiramate is about 80%. Food does not appear to affect bioavailability of the drug.
Distribution: Topiramate's volume of distribution is 0.6 to 0.8 L/kg. Approximately 15-41% of Topiramate is bound to plasma proteins, with the fraction of protein binding decreasing as blood concentration increases.
Metabolism: Minor amounts metabolized in liver via hydroxylation, hydrolysis, and glucuronidation. None of any metabolites constitutes more than 5% of an administered dose. There is evidence of renal tubular reabsorption; percentage of dose metabolized in liver and clearance are increased in patients receiving enzyme inducers (e.g. carbamazepine, phenytoin).
Elimination: Approximately 70% of an administered dose is eliminated principally in urine as unchanged drug.
The mean elimination half-life of Topiramate is summarized in the table as follows. (See Table 1.)

Click on icon to see table/diagram/image

Elimination in patients with moderate to severe renal impairment (CrCl 30-69 mL/minute/1.73 m² to less than 30 mL/minute/1.73 m²): The clearance of Topiramate was reduced by 42 or 54% respectively. However, since Topiramate also undergoes substantial tubular reabsorption, the creatinine clearance may not always predict clearance of Topiramate.
Elimination in patients undergoing hemodialysis: The clearance of Topiramate is 4-6 times more rapid than in healthy individuals.
Elimination in patients with hepatic impairment: The clearance of Topiramate may have been decreased with unknown mechanism.
Elimination in geriatric patients: Half-life elimination is longer. Plasma and renal clearance were reduced 21% and 19%, respectively. Reduced clearance resulted in slightly higher C_max and area under the curve (AUC) 23% and 25% respectively. Topiramate clearance is decreased only to the extent that renal function is reduced.
Elimination in pediatric patients: Pediatric patients have a 50% higher clearance and shorter half-life than adults.