Cole Susan, Malamatari Maria, Butler Andrew, Arshad Mahnoor, Kerwash Essam
Medicines and Healthcare Products Regulatory Agency, London, UK.
University College London, London, UK.
CPT Pharmacometrics Syst Pharmacol. 2024 Nov;13(11):1990-2001. doi: 10.1002/psp4.13260. Epub 2024 Nov 19.
Due to limited non-clinical and clinical data, European guidance recommends to discontinue breastfeeding when taking albendazole. The aim of this study was to consider the use of PBPK modeling to support the expected exposure in breastfed infants. A fully mechanistic PBPK approach was used to provide quantitative predictions of albendazole and its main active metabolite, albendazole sulfoxide, concentrations in plasma and breast milk of lactating women. The model predicted the exposure in adults and the large food effect, however, it does not predict all the clinical data for the exposure in children. Milk/plasma ratio predictions were also largely over-predicted for this lipophilic compound, but not for the less lipophilic metabolite. Predictions using the observed ratio and a worse-case exposure based on C predictions, suggest doses to children through milk will be low. However, more clinical data are required before full exposure predictions can be made to breastfed infants.
由于非临床和临床数据有限，欧洲指南建议服用阿苯达唑时停止母乳喂养。本研究的目的是考虑使用生理药代动力学（PBPK）模型来支持对母乳喂养婴儿的预期暴露量。采用了一种完全基于机制的PBPK方法，以定量预测阿苯达唑及其主要活性代谢物阿苯达唑亚砜在哺乳期妇女血浆和母乳中的浓度。该模型预测了成人的暴露量和较大的食物效应，然而，它并未预测儿童暴露量的所有临床数据。对于这种亲脂性化合物，牛奶/血浆比率预测也在很大程度上被高估，但对于亲脂性较低的代谢物则不然。使用观察到的比率和基于C预测的最坏情况暴露量进行的预测表明，通过母乳传递给儿童的剂量将很低。然而，在能够对母乳喂养婴儿进行全面暴露量预测之前，还需要更多的临床数据。
