Pharmacokinetics of tiagabine as add-on therapy in patients taking enzyme-inducing antiepilepsy drugs.
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 AUC0-6. 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.
So
E L
EL
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Wolff
D
D
Graves
N M
NM
Leppik
I E
IE
Cascino
G D
GD
Pixton
G C
GC
Gustavson
L E
LE
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002940:Circadian Rhythm / Q000502:physiology; D004790:Enzyme Induction / Q000187:drug effects; D004827:Epilepsy / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009557:Nipecotic Acids / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000078308:Tiagabine; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000927:Anticonvulsants; D009557:Nipecotic Acids; D005680:gamma-Aminobutyric Acid; D000078308:Tiagabine