title: Interaction of carbamazepine-10,11-epoxide, an active metabolite of carbamazepine, with valproate: a pharmacokinetic study.
abstract: The mechanism responsible for the valproate (VPA)-induced elevation of serum carbamazepine-10,11-epoxide (CBZ-E) levels was investigated in 6 normal subjects who received single oral doses of CBZ-E (100 mg) in a control session and during concurrent treatment with sodium VPA [500 mg twice daily (b.i.d.)]. VPA caused a significant prolongation of CBZ-E terminal half-life (t1/2 from 6.3 +/- 1.2 to 9.0 +/- 2.0 h, mean values +/- SD) and decreased CBZ-E clearance (from 90.6 +/- 18.8 to 63.2 +/- 16.1 ml h-1 kg-1, mean values +/- SD) without affecting CBZ-E apparent volume of distribution (from 0.82 +/- 0.19 to 0.81 +/- 0.24 l kg-1, mean values +/- SD). These findings indicate that VPA impairs the elimination of CBZ-E, presumably by inhibiting its metabolism.
authors.affiliation: Neurological Clinic, University of Messina, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Pisani
authors.forename: M
authors.initials: M
authors.lastname: Caputo
authors.forename: A
authors.initials: A
authors.lastname: Fazio
authors.forename: G
authors.initials: G
authors.lastname: Oteri
authors.forename: M
authors.initials: M
authors.lastname: Russo
authors.forename: E
authors.initials: E
authors.lastname: Spina
authors.forename: E
authors.initials: E
authors.lastname: Perucca
authors.forename: L
authors.initials: L
authors.lastname: Bertilsson
mesh_terms: D000042:Absorption; D000328:Adult; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D004064:Digestive System / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D002220:Carbamazepine; D014635:Valproic Acid; C012227:carbamazepine epoxide