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Predicting Chemotherapy Distribution into Breast Milk for Breastfeeding Women Using a Population Pharmacokinetic Approach
Clinical Pharmacokinetics ( IF 4.6 ) Pub Date : 2023-05-08 , DOI: 10.1007/s40262-023-01251-5
David Damoiseaux 1 , Daniel Centanni 1 , Jos H Beijnen 1, 2 , Frédéric Amant 3, 4 , Alwin D R Huitema 1, 5, 6 , Thomas P C Dorlo 1, 7
Affiliation  

Background and Objective

Information on the distribution of chemotherapeutic drugs to breast milk is scarce, and reports are limited to small sample sizes. Anecdotal pharmacokinetic data have typically been acquired from lactating but non-breastfeeding patients who collect breast milk by means of an expression pump, which might not necessarily be representative for a breastfeeding population due to differences in milk production. Consequently, little is known about the variability of chemotherapy distribution to breast milk and the effect of milk production on the distribution of chemotherapy to breast milk. Our aim was to predict chemotherapy distribution to breast milk in a more realistic breastfeeding population and evaluate the effect of discarding breast milk on the potential chemotherapy exposure in infants.

Methods

We developed a population pharmacokinetic model that described the breast milk production and the chemotherapy distribution to breast milk of a non-breastfeeding population, linked it to plasma pharmacokinetics, and extrapolated this to a breastfeeding population.

Results

We found that cumulative relative infant doses (RID) were higher than 10% for cyclophosphamide and doxorubicin and approximately 1% for paclitaxel. Simulations allowed us to predict the cumulative RID and its variability in the population for patients with different milk productions and the amount of breast milk that has to be discarded to reach cumulative RIDs below 1%, 0.1%, and 0.01%. Discarding 1–2, 3–6, and 0–1 days of breast milk (depending on the milk production of the patient) resulted in cumulative RID below 1% for cyclophosphamide, doxorubicin, and paclitaxel, respectively.

Conclusion

Our results may help clinicians to derive the optimal breast milk discarding strategy for an individual patient that wants to breastfeed during chemotherapy and minimize chemotherapy exposure in their infants.



中文翻译:


使用群体药代动力学方法预测母乳喂养妇女化疗药物在母乳中的分布


 背景和目的


有关化疗药物在母乳中分布的信息很少,而且报告仅限于小样本量。轶事药代动力学数据通常是从通过吸乳泵收集母乳的哺乳期但非母乳喂养的患者获得的,由于产奶量的差异,这可能不一定能代表母乳喂养人群。因此,人们对化疗药物在母乳中分布的变异性以及乳汁产量对化疗药物在母乳中分布的影响知之甚少。我们的目的是在更现实的母乳喂养人群中预测化疗药物在母乳中的分布,并评估丢弃母乳对婴儿潜在化疗暴露的影响。

 方法


我们开发了一个群体药代动力学模型,该模型描述了非母乳喂养人群的母乳产量和化疗药物在母乳中的分布,将其与血浆药代动力学联系起来,并将其外推到母乳喂养人群。

 结果


我们发现环磷酰胺和阿霉素的婴儿累积相对剂量 (RID) 高于 10%,紫杉醇约为 1%。通过模拟,我们能够预测具有不同产奶量的患者的累积 RID 及其在人群中的变异性,以及为使累积 RID 达到低于 1%、0.1% 和 0.01% 而必须丢弃的母乳量。丢弃 1-2、3-6 和 0-1 天的母乳(取决于患者的产奶量)分别导致环磷酰胺、阿霉素和紫杉醇的累积 RID 低于 1%。

 结论


我们的结果可以帮助临床医生为想要在化疗期间母乳喂养的个体患者制定最佳的母乳丢弃策略,并最大程度地减少婴儿的化疗暴露。

更新日期:2023-05-08
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