对胎儿暴露于母体长效注射药和口服每日抗精神病药的比较建模
Philip Bediako-Kakari1, Mariella Monyo1, Shakir Atoyebi2,3
1School of Biosciences, University of Liverpool, Liverpool, UK.
与口服形式相比,长效注射 (LAI) 抗精神病药物如阿里皮普拉和奥兰扎可能导致胎儿暴露率更高. 这些发现强调了在怀孕期间需要仔细评估好处与风险的必要性.
科学领域:
- 药理动力学和药物新陈代谢
- 产妇胎儿药理学 产妇胎儿药理学
- 计算毒理学计算毒理学
背景情况:
- 在怀孕期间使用抗精神病药物对孕产妇和胎儿的安全性提出了复杂的挑战.
- 了解胎儿药物暴露对于明智的治疗决策至关重要.
研究的目的:
- 通过使用生理学基础的药理动力学 (PBPK) 建模,比较通过口服与长效注射 (LAI) 配方的aripiprazole和 olanzapine的胎儿暴露.
- 预测胎儿暴露的关键指数和随着时间的推移累积的暴露.
主要方法:
- 使用临床数据开发和验证成人和孕妇PBPK模型.
- 对口服和LAI aripiprazole和 olanzapine 的稳定状态剂量的模拟.
- 预测胎儿最大度 (Cmax),带:母体比率,以及累计28天的胎儿暴露.
主要成果:
- 与口服药物相比,LAI配方预计会导致aripiprazole (59-78%更高) 和 olanzapine (68-181%更高) 的胎儿Cmax更高.
- 预测的带:母体比率有所变化,LAI olanzapine显示的比率比口服 olanzapine (0.34-0.64) 高 (0.89-0.96).
- 在口服配方中,累计28天的胎儿暴露通常预计低于它们的LAI等价物.
结论:
- 亚利皮普拉和奥兰扎的LAI可能会导致胎儿暴露的程度比它们的口服对应物更高.
- 这些药理动力学发现需要在更广泛的孕妇利益风险评估中仔细考虑.
- 需要对这些暴露差异的临床影响进行进一步的研究.
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