Damoiseaux David, Centanni Daniel, Beijnen Jos H, Amant Frédéric, Huitema Alwin D R, Dorlo Thomas P C
Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Clin Pharmacokinet. 2023 Jul;62(7):969-980. doi: 10.1007/s40262-023-01251-5. Epub 2023 May 8.
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.
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.
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.
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.
关于化疗药物在母乳中的分布信息匮乏，且相关报道样本量较小。轶事性的药代动力学数据通常来自于使用吸奶器收集母乳的哺乳期但非母乳喂养的患者，由于产奶量的差异，这些数据不一定能代表母乳喂养人群。因此，对于化疗药物在母乳中分布的变异性以及产奶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药物暴露的影响。
我们建立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生成及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，并外推至母乳喂养人群。
我们发现，环磷酰胺和阿霉素的累积相对婴儿剂量（RID）高于10%，紫杉醇约为1%。通过模拟，我们能够预测不同产奶量患者群体中的累积RID及其变异性，以及为使累积RID低于1%、0.1%和0.01%必须丢弃多少母乳。分别丢弃1 - 2天、3 - 6天和0 - 1天的母乳（取决于患者的产奶量），可使环磷酰胺、阿霉素和紫杉醇的累积RID低于1%。
我们的结果可能有助于临床医生为化疗期间希望进行母乳喂养的个体患者制定最佳的母乳丢弃策略，并将婴儿的化疗药物暴露降至最低。
