Pharmacokinetic interactions of progabide with other antiepileptic drugs

The influence of progabide, a new antiepileptic drug, on the pharmacokinetic profiles of phenobarbital, phenytoin, carbamazepine, and valproic acid was evaluated in four separate studies, each including six young healthy volunteers. The pharmacokinetic parameters of the associated antiepileptic drugs were measured before and after repeated administration of progabide (600 mg t.i.d.) for 15 days. A significant reduction of the total body clearance of both phenytoin and phenobarbital and a higher Cmax value of carbamazepine epoxide and phenobarbital were observed. No modifications were noticed for the kinetic profiles of carbamazepine and valproic acid. These modifications may be of clinical relevance and suggest that, as a general rule, when progabide is added to an established treatment with phenobarbital or phenytoin or carbamazepine, an adjustment of previous posology may be necessary.