EVALUATION OF THE POTENTIAL INTERACTION BETWEEN FELBAMATE AND ERYTHROMYCIN IN PATIENTS WITH EPILEPSY

Effects of erythromycin on hepatic CYP450 3A4 isozymes can profoundly influence the metabolism of many therapeutic agents. An open-label, ra ndomized, two-period, crossover study tvas therefore conducted to eval uate the pharmacokinetics of felbamate before and after a concurrent 1 0-day regimen (333 mg three times daily) of erythromycin. Patients wer e receiving either 3,000 or 3,600 mg/day felbamate monotherapy for tre atment of epilepsy. Mean dose-normalized values for maximum concentrat ion (C-max) and area under the concentration-time curve (AUC(tau)) of felbamate were not statistically different in patients faking felbamat e as monotherapy than in patients after erythromycin coadministration. Estimates of time to C-max (t(max)), minimum concentration (C-min), a pparent clearance (Cl/kg), average concentration (C-av), and degree of fluctuation (DFss) were likewise unchanged. The incidence of mild and moderate adverse events increased during coadministration of the two drugs. Because patients with epilepsy can not be treated with erythrom ycin alone, if could not be determined whether the adverse events were attributable to erythromycin or to the combination of the two drugs. Steady-state pharmacokinetic parameters of felbamate were not influenc ed by erythromycin coadministration.