Abstract
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 language | English (US) |
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Pages (from-to) | 221-226 |
Number of pages | 6 |
Journal | Epilepsy Research |
Volume | 22 |
Issue number | 3 |
DOIs | |
State | Published - Nov 1995 |
Keywords
- Diurnal variation
- Enzyme induction
- Pharmacokinetics
- Seizure
- Tiagabine
ASJC Scopus subject areas
- Neurology
- Clinical Neurology