Effect of renal impairment on the pharmacokinetics and tolerability of tiagabine.
OBJECTIVE
We wished to determine the effect of renal impairment on the pharmacokinetics and tolerability of the new antiepileptic drug tiagabine (TGB).


METHODS
We assessed TGB pharmacokinetics and tolerability in 25 subjects with various degrees of renal function (based on creatinine clearance, n = 4-6 per group) from healthy (group I) to requiring hemodialysis (group V) in a single and multiple dose (every 12 h), one-period (groups I-IV) or a single dose, two-period (group V) study (4-mg oral doses of TGB x HCl). Blood samples were collected after the first dose (both periods for group V) and after the last dose on day 5 (groups I-IV). TGB plasma concentrations and plasma protein binding were determined by high-performance liquid chromatography (HPLC) and ultrafiltration, respectively.


RESULTS
TGB was well tolerated by all study subjects. The pharmacokinetics of TGB were similar in all subjects; no pharmacokinetic parameter (based on either total or unbound concentrations) was statistically correlated with creatinine clearance. For total TGB in plasma, single-dose mean values of the maximum plasma concentration, clearance, and half-life (t(1/2)) ranged from 52 to 108 ng/ml, from 7.14 to 11.02 l/h, and from 6.4 to 8.4 h, respectively.


CONCLUSIONS
TGB pharmacokinetics and tolerability were independent of renal function; therefore, dosage adjustment is unnecessary for epilepsy patients with renal impairment.
Cato
A
A
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064-3500, USA.
Gustavson
L E
LE
Qian
J
J
El-Shourbagy
T
T
Kelly
E A
EA
D000328:Adult; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009557:Nipecotic Acids / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D011485:Protein Binding; D000078308:Tiagabine; D014462:Ultrafiltration
D000927:Anticonvulsants; D001798:Blood Proteins; D009557:Nipecotic Acids; D003404:Creatinine; D000078308:Tiagabine