Interaction of Carbamazepine‐10,11‐Epoxide, an Active Metabolite of Carbamazepine, with Valproate: A Pharmacokinetic Study

Publisher Website
Google Scholar
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.