OXCARBAZEPINE--PREGNANCY AND INFANT OUTCOME

奥卡西平——妊娠和婴儿结局

• 批准号: 2466987
• 负责人: JOAN S LOCKARD
• 金额: $ 34.49万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2466987
• 关键词: Primates; blood chemistry; brain disorder chemotherapy; carbamazepine; drug metabolism; embryo /fetus drug adverse effect; epilepsy; epoxides; female; hydroxylation; infant animal; outcomes research; postnatal growth disorder; pregnancy; prenatal growth disorder; teratogens

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most circumstances it would be detrimental to the woman's health, and perhaps that of the fetus, to have the medication withdrawn during pregnancy.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 is crucial. Carbamazepine (CBZ: Tegretol) is the drug choice in temperol lobe epilepsy and has been used as an alternative to phenytoin-induced teratogenesis. Although little is known about the actual mechanism of CBZ teratogenicity, oxidative metabolism has been implicated. Oxcarbazepine (OCBZ: Trileptal), an experimental compound in the U.S. (currently in clinical trials), seems to have equivalent efficacy to CBZ. It has been suggested as a substitute for CBZ due to its greater tolerability by patients. OCBZ is metabolized via reduction (to form a monohydroxy derivative : MHD) as compared to oxidation (CBZ). This difference results in avoidance of arene oxidee intermediaries and reactive epoxides. OCBZ thus has fewer side effects than does CBZ. However, the potential liability of OCBZ to prenatally exposed infants is completely unknown. The goal of the proposed research is to test, in a monkey model, the teratogenicity (e.g., growth problems and postnatal developmental delays) of oxcarbazepine as compared to CBZ. Comparisons will be made among several groups of infants prenatally exposed to : 1) efficacious levels of OCBZ (hydroxylative metabolism) versus carbamazepine (oxidative metabolism) and 2) matched plasma drug levels of synthesized CBZ 10, 11 - epoxide (CBZE: ongoing NIH grant) versus metabolized CBZE (via parental CBZ).

产前暴露于抗癫痫化合物后的婴儿结局是 癫痫妇女的关注很大。 在大多数情况下 会不利于女人的健康，也许是胎儿的健康 在怀孕期间取消药物。 同时， 是暴露于抗癫痫化合物的胎儿的风险，并最小化 致畸性至关重要。 卡马西平（CBZ：tegretol）是药物 选择过度叶癫痫，并已被用作替代 苯妥英钠诱导的畸胎发生。 虽然对实际的知之甚少 CBZ致致造性，氧化代谢的机制已涉及。 大西洋（Ocbazepine （目前在临床试验中）似乎与CBZ具有同等功效。 由于其更大的 患者的耐受性。 OCBZ通过还原代谢（形成A 与氧化（CBZ）相比，单羟基衍生物：MHD）。 这 差异结果避免了氧化物中介和反应性 环氧化物。 因此，OCBZ的副作用比CBZ少。 但是， OCBZ对产前暴露婴儿的潜在责任是完全的 未知。 拟议研究的目的是在猴子模型中测试 致病性（例如，生长问题和产后发育 与CBZ相比，奥沙巴西平的延迟）。 将进行比较 在几组婴儿期间暴露于：1）有效的 OCBZ（羟基代谢）与卡马西平的水平（氧化 代谢）和2）匹配的血浆药物水平合成的CBZ 10，11- 环氧（CBZE：持续的NIH赠款）与代谢CBZE（通过父母 CBZ）。