Interaction of carbamazepine-10,11-epoxide, an active metabolite of carbamazepine, with valproate: A pharmacokinetic study

F. Pisani; M. Caputo; A. Fazio; G. Oteri; M. Russo; E. Spina; E. Perucca; L. Bertilsson

Interaction of carbamazepine-10,11-epoxide, an active metabolite of carbamazepine, with valproate: A pharmacokinetic study

F. Pisani, M. Caputo, A. Fazio, G. Oteri, M. Russo, E. Spina, E. Perucca, L. Bertilsson

Fondazione "Istituto Neurologico Casimiro Mondino"

Research output: Contribution to journal › Article › peer-review

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 (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.

Original language	English
Pages (from-to)	339-342
Number of pages	4
Journal	Epilepsia
Volume	31
Issue number	3
Publication status	Published - 1990

Keywords

Anti-convulsants
Carbamazepine-epoxide
Drug interactions
Valproate

ASJC Scopus subject areas

Clinical Neurology
Neuroscience(all)

Cite this

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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 (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.",

keywords = "Anti-convulsants, Carbamazepine-epoxide, Drug interactions, Valproate",

author = "F. Pisani and M. Caputo and A. Fazio and G. Oteri and M. Russo and E. Spina and E. Perucca and L. Bertilsson",

year = "1990",

language = "English",

volume = "31",

pages = "339--342",

journal = "Epilepsia",

issn = "0013-9580",

publisher = "Blackwell Publishing Inc.",

number = "3",

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TY - JOUR

T1 - Interaction of carbamazepine-10,11-epoxide, an active metabolite of carbamazepine, with valproate

T2 - A pharmacokinetic study

AU - Pisani, F.

AU - Caputo, M.

AU - Fazio, A.

AU - Oteri, G.

AU - Russo, M.

AU - Spina, E.

AU - Perucca, E.

AU - Bertilsson, L.

PY - 1990

Y1 - 1990

N2 - 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.

AB - 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.

KW - Anti-convulsants

KW - Carbamazepine-epoxide

KW - Drug interactions

KW - Valproate

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M3 - Article

C2 - 2111769

AN - SCOPUS:0025298705

SN - 0013-9580

VL - 31

SP - 339

EP - 342

JO - Epilepsia

JF - Epilepsia

IS - 3

ER -

Interaction of carbamazepine-10,11-epoxide, an active metabolite of carbamazepine, with valproate: A pharmacokinetic study

Abstract

Keywords

ASJC Scopus subject areas

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