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Evaluation of the Potential Interaction Between Felbamate and Erythromycin in Patients with Epilepsy
Author(s) -
Sachdeo Rajesh C.,
NarangSachdeo Satinder,
Montgomery Paul A.,
Shumaker Robert C.,
Perhach James L.,
Lyness William H.,
Rosenberg Alberto
Publication year - 1998
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1998.tb04409.x
Subject(s) - felbamate , erythromycin , pharmacokinetics , crossover study , pharmacology , adverse effect , epilepsy , drug interaction , anticonvulsant , medicine , pharmacokinetic interaction , chemistry , antibiotics , biochemistry , alternative medicine , pathology , psychiatry , placebo
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 (C max ) and area under the concentration—time curve (AUC r ) of felbamate were not statistically different in patients taking felbamate as monotherapy than in patients after erythromycin coadministration. Estimates of time to C max (t max ), minimum concentration (C min ), apparent clearance (Cl/kg), average concentration (C av ), and degree of fluctuation (DF ss ) 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.