Van Neste Martje, Nauwelaerts Nina, Mols Raf, Krutsch Kaytlin, Ceulemans Michael, Passier Anneke, Smits Anne, Annaert Pieter, Allegaert Karel
Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Child and Youth institute, KU Leuven, Leuven, Belgium.
Front Pharmacol. 2025 Apr 1;16:1499243. doi: 10.3389/fphar.2025.1499243. eCollection 2025.
Implementation of breastfeeding recommendations is hampered by-among others-lacking information regarding medicine safety during breastfeeding. This article describes the clinical and pharmacokinetic data of breastfeeding mothers using clopidogrel (CLP) as secondary prevention following (suspicion of) a cerebrovascular accident.
A 29-year-old and 42-year-old woman were chronically treated with 75 mg CLP once daily. Human milk samples were collected at 7 and 9 months (patient 1), and at 14 months (patient 2). Each sampling period, two maternal blood samples as well as one infant blood sample were collected. Concentrations of CLP, clopidogrel carboxylic acid (CCA) and clopidogrel active metabolite (CAM) derivatized were analyzed using liquid chromatography with tandem mass spectrometry.
The average steady-state concentration in human milk was 0.96 and 7.40 ng/mL for CLP and CCA, respectively. CAM concentrations in all but two milk samples were below the limit of detection (LOD; 0.004 ng/mL). In the infant plasma sample, CCA level was 0.05 ng/mL but CLP and CAM were undetectable (CLP LOD: 0.003 ng/mL). The mean daily infant dosage (DID) was 82.3, 585.6 and 1.5 ng/kg/day for CLP, CCA and CAM, respectively, and the relative infant dose (RID) for CLP-related exposure remained well below 1%.
The estimated infant exposure to CLP and its metabolites via human milk was low in both cases. Although this low exposure was supported by the observed infant plasma concentration, additional studies should confirm CLP safety via human milk, especially considering known variable pharmacokinetics and ontogeny of metabolizing enzymes in infants.
母乳喂养建议的实施受到多种因素的阻碍，其中包括缺乏关于母乳喂养期间药物安全性的信息。本文描述了在（疑似）脑血管意外后使用氯吡格雷（CLP）进行二级预防的母乳喂养母亲的临床和药代动力学数据。
一名29岁和一名42岁的女性长期每日一次服用75毫克CLP。分别在7个月和9个月（患者1）以及14个月（患者2）采集母乳样本。在每个采样期，采集两份母亲血液样本以及一份婴儿血液样本。使用液相色谱 - 串联质谱法分析CLP、氯吡格雷羧酸（CCA）和衍生化的氯吡格雷活性代谢物（CAM）的浓度。
母乳中CLP和CCA的平均稳态浓度分别为0.96和7.40纳克/毫升。除两份母乳样本外，所有样本中的CAM浓度均低于检测限（LOD；0.004纳克/毫升）。在婴儿血浆样本中，CCA水平为0.05纳克/毫升，但未检测到CLP和CAM（CLP LOD：0.003纳克/毫升）。CLP、CCA和CAM的平均每日婴儿剂量（DID）分别为82.3、585.6和1.5纳克/千克/天，与CLP相关暴露的相对婴儿剂量（RID）仍远低于1%。
在这两个案例中，估计婴儿通过母乳接触CLP及其代谢物的量都很低。尽管观察到的婴儿血浆浓度支持了这种低暴露，但仍需进一步研究以确认CLP通过母乳的安全性，特别是考虑到婴儿已知的可变药代动力学和代谢酶的个体发育情况。
