title: Influence of additional therapy with zonisamide (Excegran) on protein binding and metabolism of carbamazepine.
abstract: The influence of comedication with zonisamide (ZNS) on protein binding and carbamazepine (CBZ) metabolism was studied in 16 pediatric epileptic patients. Correlations were evaluated between ZNS daily dose and individual change of level per dose ratio (L/D ratio), free fraction, and carbamazepine-10,11-epoxide/CBZ level ratio (CBZE/CBZ). Statistical significant negative correlation was observed between L/D ratio and ZNS daily dose. Despite alteration in the L/D ratio, the free fraction of CBZ was unaltered in combination with ZNS. To assess the effect of addition of ZNS on CBZ metabolism, the CBZE/CBZ level ratio was compared; this ratio showed a tendency to increase with increase in ZNS dose. Consequently, ZNS is considered to have a significant effect on CBZ metabolism but not on protein binding.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Minami
authors.forename: I
authors.initials: I
authors.lastname: Ieiri
authors.forename: K
authors.initials: K
authors.lastname: Ohtsubo
authors.forename: Y
authors.initials: Y
authors.lastname: Hirakawa
authors.forename: K
authors.initials: K
authors.lastname: Ueda
authors.forename: S
authors.initials: S
authors.lastname: Higuchi
authors.forename: T
authors.initials: T
authors.lastname: Aoyama
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000627:therapeutic use*; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D000078305:Zonisamide
chemical_list: D000927:Anticonvulsants; D007555:Isoxazoles; D002220:Carbamazepine; D000078305:Zonisamide; C012227:carbamazepine epoxide