title: Evaluation of the potential interaction between felbamate and erythromycin in patients with epilepsy.
abstract: Effects of erythromycin on hepatic CYP450 3A4 isozymes can profoundly influence the metabolism of many therapeutic agents. An open-label, randomized, two-period, crossover study was therefore conducted to evaluate the pharmacokinetics of felbamate before and after a concurrent 10-day regimen (333 mg three times daily) of erythromycin. Patients were receiving either 3,000 or 3,600 mg/day felbamate monotherapy for treatment of epilepsy. Mean dose-normalized values for maximum concentration (Cmax) and area under the concentration-time curve (AUC tau) of felbamate were not statistically different in patients taking felbamate as monotherapy than in patients after erythromycin coadministration. Estimates of time to Cmax (tmax), minimum concentration (Cmin), apparent clearance (Cl/kg), average concentration (Cav), 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 erythromycin alone, it 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 influenced by erythromycin coadministration.
authors.affiliation: Department of Neurology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Sachdeo
authors.forename: S
authors.initials: S
authors.lastname: Narang-Sachdeo
authors.forename: P A
authors.initials: PA
authors.lastname: Montgomery
authors.forename: R C
authors.initials: RC
authors.lastname: Shumaker
authors.forename: J L
authors.initials: JL
authors.lastname: Perhach
authors.forename: W H
authors.initials: WH
authors.lastname: Lyness
authors.forename: A
authors.initials: A
authors.lastname: Rosenberg
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000097:blood* / Q000494:pharmacology; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018592:Cross-Over Studies; D004347:Drug Interactions; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D004917:Erythromycin / Q000097:blood* / Q000494:pharmacology; D000078328:Felbamate; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008875:Middle Aged; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D004917:Erythromycin; D000078328:Felbamate