OXCARBAZEPINE PREGNANCY & INFANT OUTCOME

奥卡西平妊娠

• 批准号: 6116314
• 负责人: JOAN S LOCKARD
• 金额: $ 8.67万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116314
• 关键词: Mammalia; Primates; congenital disorders; drug /agent; growth /development; mother /infant health care; nervous system

Infant outcome after prenatal exposure to antiepileptic compounds is of considerable concern to women with epilepsy. Under most circumstances, it would be detrimental to the woman's health, and perhaps that of the fetus, to have the medication withdrawn during pregnancy. At the same time, there is risk to the fetus exposed to antiepileptic compounds, and minimizing teratogenicity (e.g., growth problems and postnatal developmental delays) is of considerable importance. Carbamazepine (CBZ Tegretol() is currently the drug of choice in temporal lobe epilepsy and has been used as an alternative to phenytoin (PHT Dilantin(), which is known to induce teratogenicity. Although little is known about the actual mechanism of CBZ teratogenicity, oxidative metabolism has been implicated. Oxcarbazepine (OCBZ Trileptol(), an experimental compound in the U.S. (currently in clinical use in Europe), seems to be as efficacious as CBZ and has been suggested as a substitute for CBZ owing to its greater tolerability by patients. OCBZ is metabolized via reduction to form a monohydroxy derivative, whereas CBZ is oxidized to form an epoxide. This difference avoids the formation of reactive arene oxides and epoxides possibly responsible for the teratogenicity of CBZ. However, the potential liability of OCBZ to prenatally exposed infants is completely unknown. The goal of this research project is to test the teratogenicity of oxcarbazepine in a monkey model. To date, 15 females and 3 breeder males are on study. Nine of the animals are on preliminary kinetics studies to determine the OCBZ dosing design for the pregnancy studies. The remaining six animals are on a CBZ or control regimen and will produce infants that will be compared with OCBZ-exposed infants in the postnatal studies. Two infants are due to be born in February 1998.

在产前暴露于抗癫痫化合物的情况下，婴儿的癫痫女性具有相当大的关注。 在大多数情况下，在怀孕期间撤离药物会不利于该妇女的健康，也许是胎儿的健康。 同时，暴露于抗癫痫化合物的胎儿存在风险，并最大程度地减少了致畸性（例如，生长问题和产后发育迟缓）非常重要。 卡马西平（CBZ tegretol（）目前是颞叶癫痫中首选的药物，已被用作苯妥英钠的替代品（Pht dilantin（），众所周知，这是诱导致畸性的。尽管对CBz teratientienty的实际机制众所周知，氧化代理（氧化代理）尤其是氧化型（氧化剂）。美国的实验性化合物（目前在欧洲的临床用途）似乎与CBZ一样有效，由于CBZ的耐受性更高，因此被认为是替代CBZ，通过还原来代谢，以形成单羟基衍生物，而CBZ则氧有氧化的氧化物。然而，CBZ的致病性。是在CBZ或对照方案上，将产生与OCBZ暴露于产后研究的婴儿。