Metabolism of carbamazepine and co-administered anticonvulsants during pregnancy

Bernus I., Hooper W.D., Dickinson R.G. and Eadie M.J. (1995) Metabolism of carbamazepine and co-administered anticonvulsants during pregnancy. Epilepsy Research, 21 1: 65-75. doi:10.1016/0920-1211(95)00012-Y


Author Bernus I.
Hooper W.D.
Dickinson R.G.
Eadie M.J.
Title Metabolism of carbamazepine and co-administered anticonvulsants during pregnancy
Journal name Epilepsy Research   Check publisher's open access policy
ISSN 0920-1211
Publication date 1995-01-01
Sub-type Article (original research)
DOI 10.1016/0920-1211(95)00012-Y
Open Access Status Not yet assessed
Volume 21
Issue 1
Start page 65
End page 75
Total pages 11
Subject 2728 Clinical Neurology
2808 Neurology
2735 Pediatrics, Perinatology, and Child Health
Abstract Urinary excretions of carbamazepine, carbamazepine-10,11-epoxide, carbamazepine-10,11-trans-diol, 9-hydroxyacridan and 2- and 3-hydroxycarbamazepine were measured at various stages of pregnancy, and in the post-natal period, in ten epileptic women, six of whom took no other enzyme-inducing anticonvulsant and four of whom took such co-medication. Mean plasma carbamazepine apparent clearance was increased in pregnancy, but only by virtue of the increased clearance in the anticonvulsant co-medicated women. Alterations in the proportions of the carbamazepine dose cleared via the various excretion pathways studied were quantitatively minor, but there was evidence consistent with impaired conversion of carbamazepine-10,11-epoxide to carbamazepine-10,11-trans-diol during all pregnancies studied. Clearances of carbamazepine to the various excretory products studied were consistent with there being (i) increased urinary excretion of unmetabolised drug in pregnancy, possibly related to the increased glomerular filtration rate, (ii) increased formation of oxidative metabolites of the drug, particularly in women co-medicated with enzyme-inducing anticonvulsants, this effect being offset, in full (in non-co-medicated women) or in part (in co-medicated women) by (iii) inhibition of the epoxide-diol pathway in pregnancy, an inhibition to which folate intake may have contributed.
Keyword Carbamazepine
Drug metabolism
Methylphenobarbitone
Phenytoin
Pregnancy
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import - Archived
 
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