The pharmacokinetics of tiagabine in healthy elderly volunteers and elderly patients with epilepsy.
The pharmacokinetics of tiagabine after single-dose (8 mg) and multiple-dose (3 mg, three-times daily for four days) administration of tiagabine HCl were investigated in healthy elderly volunteers (n = 8; Group 1), elderly patients with epilepsy receiving at least one hepatic enzyme-inducing antiepileptic drug (AED) (n = 8; Group 2), and healthy young volunteers (n = 8; Group 3). Participants were matched by gender, age (Groups 1 and 2), alcohol intake, body weight, and whether they smoked tobacco. The pharmacokinetic parameters of tiagabine following single- and multiple-dose administration were similar in both healthy elderly and young volunteers except for a small but significant difference in the area under the concentration-time curve after multiple-doses (103 +/- 29 ng.hr/mL/mg in the elderly versus 72 +/- 20 ng.hr/mL/mg in younger participants). This is not expected to have any clinical relevance because of the large intersubject variability in this parameter. In contrast, and as expected, the pharmacokinetics of tiagabine were altered in the presence of enzyme-inducing antiepileptic drugs: Time to reach maximum plasma concentration, area under the concentration-time curve, and elimination half-lives were significantly lower (e.g. 39 +/- 13 ng.hr/mL/mg for AUC after multiple-dose) compared with corresponding values in the healthy volunteers. These findings suggest that adjusting the dose of tiagabine on the basis of the age of the patient is not necessary, although, irrespective of age, higher doses and/or more frequent administrations will be required in patients taking concomitant enzyme-inducing antiepileptic drugs.