Bernus I, Hooper W D, Dickinson R G, Eadie M J
Department of Medicine, University of Queensland, Royal Brisbane Hospital, Herston, Australia.
Epilepsy Res. 1995 May;21(1):65-75. doi: 10.1016/0920-1211(95)00012-y.
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.
对10名癫痫女性在孕期不同阶段及产后阶段的尿液中卡马西平、卡马西平 - 10,11 - 环氧化物、卡马西平 - 10,11 - 反式二醇、9 - 羟基吖啶以及2 - 和3 - 羟基卡马西平的排泄量进行了测量。其中6名女性未服用其他酶诱导性抗惊厥药物，4名女性同时服用了此类联合药物。孕期平均血浆卡马西平表观清除率升高，但仅因同时服用抗惊厥联合药物的女性清除率增加。通过所研究的各种排泄途径清除的卡马西平剂量比例的变化在数量上较小，但有证据表明在所有研究的孕期中，卡马西平 - 10,11 - 环氧化物向卡马西平 - 10,11 - 反式二醇的转化受损。卡马西平向所研究的各种排泄产物的清除率表明：（i）孕期未代谢药物的尿排泄增加，可能与肾小球滤过率增加有关；（ii）药物氧化代谢产物的形成增加，特别是在同时服用酶诱导性抗惊厥药物的女性中，这种效应在（未联合用药的女性中）被完全抵消，或在（联合用药的女性中）被部分抵消，原因是（iii）孕期环氧二醇途径受到抑制，叶酸摄入可能对此抑制作用有影响。
