Effect of Renal Impairment on the Pharmacokinetics and Tolerability of Tiagabine

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Abstract
We wished to determine the effect of renal impairment on the pharmacokinetics and tolerability of the new antiepileptic drug tiagabine (TGB). 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. 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. TGB pharmacokinetics and tolerability were independent of renal function; therefore, dosage adjustment is unnecessary for epilepsy patients with renal impairment.