Pharmacokinetics of tiagabine as add-on therapy in patients taking enzyme-inducing antiepilepsy drugs

Elson L. So, Denise Wolff, Nina M. Graves, Ilo E. Leppik, Gregory D. Cascino, Glenn C. Pixton, Linda E. Gustavson

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The effect of hepatic enzyme-inducing antiepilepsy drugs (AEDs) on the clinical pharmacokinetics of tiagabine, a new AED, was studied in the steady-state condition. Patients with epilepsy entered this two-day study on a previously stable regimen of one to three enzyme-inducing drugs (phenytoin, phenobarbital, carbamazepine, and/or primidone) and tiagabine · HCl (24, 40, 56, or 80 mg daily). Patients were confined on both days, and serial blood samples were collected. Plasma tiagabine concentrations were determined by high-performance liquid chromatography; pharmacokinetic parameters were calculated using noncompartmental methods. Tiagabine pharmacokinetics were linear at all doses, as substantiated by the lack of significant differences among groups for dose-adjusted Cmax, Cmin, and AUC0-6. Some diurnal variation occurred, as evidenced by a statistically significant time effect for dose-adjusted AUC2-6. The effect was small, however, and possibly not clinically relevant. The harmonic mean half-lives of 3.8 to 4.9 h were remarkably constant across dosages and shorter than those of historical control subjects not taking enzyme-inducing AEDs suggesting that epilepsy patients not taking enzyme-inducing AEDs may require lower tiagabine · HCl doses to achieve the plasma levels observed in patients taking these drugs.

Original languageEnglish (US)
Pages (from-to)221-226
Number of pages6
JournalEpilepsy Research
Issue number3
StatePublished - Nov 1995

Bibliographical note

Funding Information:
This work was supportedb y grantsf rom Abbott LaboratoriesN, orth Chicago, Illinois, USA, and Novo NordiskA /S, CopenhagenD,e nmark.


  • Diurnal variation
  • Enzyme induction
  • Pharmacokinetics
  • Seizure
  • Tiagabine


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