Influence of Comedication on Levetiracetam Pharmacokinetics.

Abstract

To evaluate the effect of concomitant antiepileptic therapy on levetiracetam (LEV) pharmacokinetics. A 6-year retrospective observational study. Patients were grouped according to the antiepileptic drug used as concomitant medication: group A, LEV in monotherapy; group B, LEV + enzyme-inducing antiepileptic drugs (EIAEDs); and group C, LEV + non-enzyme-inducing antiepileptic drugs (NEIAEDs). Apparent oral levetiracetam clearance (LEV CL/F) and basal serum levetiracetam concentrations (LEV C0) were compared among the different groups by analysis of variance. A total of 330 LEV C0 corresponding to 205 patients (56% men) were identified. The mean (±SD) of LEV CL/F in group A (n = 180), B (n = 92), and C (n = 58) was 4.41 ± 2.06 L/h, 7.23 ± 3.72 L/h, and 4.87 ± 1.65 L/h, respectively. EIAEDs increased LEV CL/F (L/h) by 64% compared with the monotherapy group and by 48% compared with the NEIAEDs group. The greatest induction in LEV CL/F, compared with the LEV monotherapy group, was observed with carbamazepine, followed by oxcarbazepine and phenobarbital, and was increased by 81%, 64%, and 44%, respectively. LEV C0 values were significantly lower in the EIAEDs group than in the monotherapy group (17.30 ± 7.77 versus 20.08 ± 9.69 mcg/mL; P = 0.038) or indeed the NEIAEDs group (17.30 ± 7.77 versus 20.49 ± 9.46 mcg/mL; P = 0.027). Comedication with EIAEDs increased LEV CL/F by more than 40%, whereas carbamazepine had the greatest inducing potency with LEV CL/F being 81% higher than that of the monotherapy group. These data suggest that monitoring LEV serum concentration during polytherapy with EIAEDs is indicated.