Le. Gustavson et Hb. Mengel, PHARMACOKINETICS OF TIAGABINE, A GAMMA-AMINOBUTYRIC ACID-UPTAKE INHIBITOR, IN HEALTHY-SUBJECTS AFTER SINGLE AND MULTIPLE DOSES, Epilepsia, 36(6), 1995, pp. 605-611
Tiagabine (TGB) HCl, a new antiepileptic compound, is a potent and spe
cific inhibitor of gamma-aminobutyric acid (GABA) uptake. In conjuncti
on with three phase I studies, the pharmacokinetics of TGB were examin
ed in 58 healthy male volunteers. Study I involved single increasing d
oses (2-24 mg TGB HCl); study II involved doses of 2-10 mg given once
daily for 5 days; study III explored one dose daily (6 or 12 mg) for 1
4 consecutive days. Plasma TGB concentrations were measured by high-pe
rformance liquid chromatography (HPLC). Pharmacokinetic parameters wer
e calculated by standard noncompartmental methods. Pharmacokinetic pro
files were similar in all three studies and indicated that the process
es of absorption and elimination of TGB were linear. The drug was rapi
dly absorbed, and half-life (t1/2) averaged 5-8 h. The accumulation ra
tio was fairly low: < 1.4 in most subjects. Secondary peaks in plasma
concentration-time profiles suggested enterohepatic recycling. Lack of
significant effects on antipyrine clearance indicated that TGB does n
ot induce or inhibit hepatic microsomal enzyme systems.