title: Lack of a clinically significant effect of zonisamide on phenytoin steady-state pharmacokinetics in patients with epilepsy.
abstract: This study was designed to measure the effect of the addition of zonisamide on phenytoin pharmacokinetics under steady-state conditions in patients with epilepsy. Nineteen patients stabilized under phenytoin monotherapy were included in a 3-center, open-label, 1-way drug interaction trial. Zonisamide was gradually increased to 400 mg/day, taken twice daily. Three pharmacokinetic profiles were performed: on days -7 and -1, to assess pharmacokinetic parameters of oral phenytoin administered alone, and on day 35, after 14 days of zonisamide treatment, to evaluate the effect of zonisamide on phenytoin pharmacokinetics and to characterize zonisamide pharmacokinetics in the presence of phenytoin. Fourteen patients completed the study; the coadministration of zonisamide and phenytoin was safe and well tolerated. Zonisamide did not significantly affect the mean C(min), C(max), AUC(0-12), and CL/F of phenytoin measured before and after zonisamide administration. The pharmacokinetic measures of zonisamide in the presence of phenytoin were consistent with previous reports of induction of zonisamide metabolism by phenytoin.
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, Washington 98195, USA.
authors.forename: René H
authors.initials: RH
authors.lastname: Levy
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ragueneau-Majlessi
authors.forename: William R
authors.initials: WR
authors.lastname: Garnett
authors.forename: Michael
authors.initials: M
authors.lastname: Schmerler
authors.forename: William
authors.initials: W
authors.lastname: Rosenfeld
authors.forename: Jaymin
authors.initials: J
authors.lastname: Shah
authors.forename: Wei-Jian
authors.initials: WJ
authors.lastname: Pan
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D019540:Area Under Curve; D004347:Drug Interactions; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010672:Phenytoin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000078305:Zonisamide
chemical_list: D000927:Anticonvulsants; D007555:Isoxazoles; D000078305:Zonisamide; D010672:Phenytoin