Tiagabine: a novel antiepileptic drug

OBJECTIVE: To provide a comprehensive review of tiagabine, including its pharmacology, toxicology, pharmacokinetics, drug interactions, efficacy, adverse effects, and dosing recommendations. DATA SOURCES: A computerized search of the MEDLINE database from 1966 to December 1997 was used to identify publications related to tiagabine and nipecotic acid derivatives. Included in this review was information gathered from scientific meetings. Manufacturer's information was used when there was no primary literature. DATA SYNTHESIS: Tiagabine amplifies gamma-aminobutyric acid (GABA) neurotransmission, the predominant inhibitory neurotransmitter in the brain. Its mechanism of action is selective and has shown promise as an antiepileptic drug (AED) in patients with seizures refractory to other pharmaceutical products. Tiagabine exhibits dose-independent absorption, 90-95% bioavailability, high protein binding (96%), metabolism via hepatic cytochrome P450 enzymes (CYP3A subfamily), and displays first-order elimination pharmacokinetics. The mean plasma half-life is 5-8 hours. Concomitant medications that induce hepatic metabolism enhance tiagabine elimination; metabolism is reduced in patients with hepatic dysfunction. Adverse events of tiagabine typically involve the central nervous system, have been mild to moderate in intensity, and also have been transient in nature. CONCLUSIONS: Tiagabine has demonstrated a good safety profile and, while it has not been demonstrated to be superior to other second-line AEDs for partial seizures, its safety and select mechanism of action warrant its further evaluation in the clinical setting. Tiagabine should be a good alternative add-on agent for patients with unsatisfactory seizure control or intolerable adverse effects of traditional therapies; thus, this agent should be made available to these patients.