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Pharmacokinetics of Tiagabine, a γ‐Aminobutyric Acid‐Uptake Inhibitor, in Healthy Subjects After Single and Multiple Doses
Author(s) -
Gustavson Linda E.,
Mengel Helle B.
Publication year - 1995
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.1995.tb02575.x
Subject(s) - tiagabine , pharmacokinetics , anticonvulsant , pharmacology , aminobutyric acid , nipecotic acid , medicine , epilepsy , anesthesia , neurotransmitter , psychiatry , central nervous system , receptor
Summary: Tiagabine (TGB) HC1, a new antiepilepticcompound, is a potent and specific inhibitor of γ‐aminobutyric acid (GABA) uptake. In conjunction with threephase I studies, the pharmacokinetics of TGB were examined in 58 healthy male volunteers. Study I involvedsingle increasing doses (2–24 mg TGB HC1); 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 14consecutive days. Plasma TGB concentrations were measured by high‐performance liquid chromatography(HPLC). Pharmacokineticprofiles were similar in all three studies and indicated thatthe processes of absorption and elimination of TGB werelinear. The drug was rapidly absorbed, and half‐life (tV2)averaged 5–8 h. The accumulation ratio was fairly low:1.4 in most subjects. Secondary peaks in plasma concentration‐time profiles suggested enterohepatic recycling. Lack of significant effects on antipyrine clearanceindicated that TGB does not induce or inhibit hepaticmicrosomal enzyme systems.