Top Gene Interactions
- Metabolism: Not extensively metabolized, 70% of the dose is eliminated unchanged in the urine. The other 30% is metabolized hepatically to six metabolites (formed by hydroxylation, hydrolysis, and glucuronidation), none of which constitute more than 5% of an administered dose. There is evidence of renal tubular reabsorption of topiramate. Route of Elimination: Topiramate is not extensively metabolized and is primarily eliminated unchanged in the urine (approximately 70% of an administered dose). Half Life: 19 to 23 hours. The mean elimination half-life was 31 hours following repeat administration of the extended-release formulation.
- Uses/Sources: Used for the treatment and control of partial seizures and severe tonic-clonic (grand mal) seizures and also for the prevention of migraine headaches. Used to treat epilepsy in children and adults. It is sometimes used as an antidepressant. In children it is indicated for the treatment of Lennox-Gastaut syndrome, a disorder that causes seizures and developmental delay. It is also Food and Drug Administration (FDA) approved for, and most frequently prescribed for, the prevention of migraines. Psychiatrists have used topiramate to treat bipolar disorder, but it is not FDA approved for this purpose. This drug has been investigated for use in treating alcoholism and obesity, especially to reduce binge eating.
- Health Effects: May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
- Symptoms: Symptoms of overdose include abdominal pain, agitation, blurred vision, convulsions, depression, dizziness, double vision, drowsiness, impaired coordination, impaired mental activity, low blood pressure, reduced consciousness, severe diarrhea, sluggishness, and speech problems.
- Treatment: In acute Topiramate overdose, if the ingestion is recent, the stomach should be emptied immediately by lavage or by induction of emesis. Activated charcoal has been shown to adsorb topiramate in vitro. Treatment should be appropriately supportive. Hemodialysis is an effective means of removing topiramate from the body. (L1712)
- Route of Exposure: Oral. Rapid with pleak plasma concentrations occurring after 2 hours and a bioavailability of 80%. The pharmacokinetic profile of the extended release formulation is non linear at 25 mg due to binding of topiramate to carbonic anhydrase in red blood cells. The peak plasma concentration was 24 hours after a single 200 mg oral dose of the extended release formulation. It is also bioequivalent to immediate-release tablet that has been administered twice-daily. Fluctuation of topiramate plasma concentrations at steady-state for Trokendi XR® administered once-daily was approximately 26% and 42% in healthy subjects and in epileptic patients, respectively, compared to approximately 40% and 51%, respectively, for immediate-release topiramate. When topiramate is given to elderly and young adults, the maximum plasma concentration was achieved in 1 to 2 hours.
Mechanism of Action
|Target Name||Mechanism of Action||References|
Carbonic anhydrase 1
Carbonic anhydrase 3
Carbonic anhydrase 5A, mitochondrial
GABA-A receptor (anion channel)
Gamma-aminobutyric acid receptor subunit alpha-1
Carbonic anhydrase 2
Carbonic anhydrase 4
Sodium channel protein type 1 subunit alpha
Glutamate receptor ionotropic, kainate 1
|The precise mechanism of action of topiramate is not known. However, studies have shown that topiramate blocks the action potentials elicited repetitively by a sustained depolarization of the neurons in a time-dependent manner, suggesting a state-dependent sodium channel blocking action. Topiramate also augments the activity of the neurotransmitter gamma-aminobutyrate (GABA) at some subtypes of the GABAA receptor (controls an integral chloride channel), indicating a possible mechanism through potentiation of the activity of GABA. Topiramate also demonstrates antagonism of the AMPA/kainate subtype of the glutamat excitatory amino acid receptor. It also inhibits carbonic anhydrase (particularly isozymes II and IV), but this action is weak and unlikely to be related to its anticonvulsant actions.||
Topiramate Interacts with Diseases
|Disease||Inference Score||References/Inference Genes|
|Liver Cirrhosis, Experimental||16.28||
|Diabetes Mellitus, Experimental||13.49||
|Adrenal Hyperplasia, Congenital||12.78||
|Epilepsy, Temporal Lobe||9.04||
|Carcinoma, squamous cell of head and neck||8.56||
|Infarction, Middle Cerebral Artery||7.87||