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Tiagabine (Gabitril) is indicated as adjunctive therapy in adults and children 12 years and older in the treatment of partial seizures. It is frequently administered to patients receiving at least 1 concomitant antiepileptic drug (AED). Tiagabine is a selective blocker of gamma-aminobutyric acid (GABA) uptake into presynaptic neurons. Tiagabine binds to recognition sites associated with the GABA uptake carrier. By this action, tiagabine blocks GABA uptake into presynaptic neurons, permitting more GABA to be available for receptor binding on the surface of postsynaptic cells.
Tiagabine has an elimination half-life of 7 to 9 hours in normal volunteers. In patients receiving enzyme-inducing AEDs, the elimination half-life decreases to 4 to 7 hours. Phenytoin, phenobarbital, and carbamazepine are AED enzyme inducers; valproate and gabapentin are not. Tiagabine is not considered to be an enzyme-inducing AED.
Tiagabine reaches peak serum concentration approximately 45 minutes following an oral dose in the fasting state. Tiagabine is well absorbed with food slowing the absorption rate but not altering the extent of absorption (high-fat diet prolongs peak serum concentrations to about 2.5 hours). Tiagabine is >95% absorbed, with oral bioavailability of about 90%. Tiagabine pharmacokinetics are linear over the typical dose range of 2 to 24 mg. Steady-state is achieved within 2 days. Tiagabine is 96% bound to human plasma proteins, mainly to serum albumin and alpha-1-acid glycoprotein. Coadministration with valproate reduces protein binding to 94%, increasing the free fraction of tiagabine by 40%.
Based on in vitro data, tiagabine is likely to be metabolized by the 3A isoform subfamily of hepatic cytochrome P450 (CYP 3A), although contributions to the metabolism from CYP 1A2, CYP 2D06, or CYP 2C19 have not been excluded.
Because tiagabine has a wide therapeutic index and dose-dependent toxicity, routine drug monitoring is not indicated in all patients. Drug monitoring is indicated when initiating concomitant therapy with antiepileptic drugs that induce hepatic enzymes and when the patient does not respond to treatment, to ascertain whether treatment failure is due to noncompliance or nonresponse to the drug.
Monitoring tiagabine therapy
Trough tiagabine serum concentrations are in the range of 20 to 200 ng/mL in most patients receiving therapeutic doses. Tiagabine serum concentration is proportional to dose. Serum concentrations >800 ng/mL indicate excessive dosing associated with adverse effects such as asthenia, ataxia, difficulty concentrating, and depression.
Drugs that may interfere with the internal standard include verapamil, lorazepam, and bupivacaine. Coadministration of these drugs will generate an artifactually decreased tiagabine concentration.
Trough: 20-200 ng/mL
1. Hiemke C, Baumann P, Bergemann N, et al: AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: update 2011. Pharmacopsychiatry 2011;44:195-235
2. Burtis C, Ashwood E, Bruns D: Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Elsevier, Mosby, Saunders, 2011