THE PHARMACOKINETICS OF TIAGABINE IN HEALTHY ELDERLY VOLUNTEERS AND ELDERLY PATIENTS WITH EPILEPSY

The pharmacokinetics of tiagabine after single-dose (8 mg) and multipl e-dose (3 mg, three-times daily for four days) administration of tiaga bine HCl were investigated in healthy elderly volunteers (n = 8; Group 1), elderly patients with epilepsy receiving at least one hepatic enz yme-inducing antiepileptic drug (AED) (n = 8; Group 2), and healthy yo ung volunteers (n = 8; Group 3). Participants were matched by gender, age (Groups 1 and 2), alcohol intake, body weight, and whether they sm oked tobacco. The pharmacokinetic parameters of tiagabine following si ngle-and multiple-dose administration were similar in both healthy eld erly and young volunteers except for a small but significant differenc e 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 rele vance 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 t o reach maximum plasma concentration, area under the concentration-tim e curve, and elimination half-lives were significantly lower (e.g. 39 +/- 13 ng.hr/mL/mg for AUC after multiple-dose) compared with correspo nding values in the healthy volunteers. These findings suggest that ad justing the dose of tiagabine on the basis of the age of the patient i s not necessary, although, irrespective of age, higher doses and/or mo re frequent administrations will be required in patients taking concom itant enzyme-inducing antiepileptic drugs.