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 (t 1/2 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.
|Number of pages||4|
|Publication status||Published - 1990|
- Drug interactions
ASJC Scopus subject areas
- Clinical Neurology