Department of Pharmaceuticals, National Center for Child Health and Development, Tokyo, Japan.
Japan Drug Information Institute in Pregnancy, National Center for Child Health and Development, Tokyo, Japan.
Int J Rheum Dis. 2019 Jun;22(6):1130-1137. doi: 10.1111/1756-185X.13557. Epub 2019 Apr 10.
Tocilizumab (TCZ), a humanized anti-interleukin-6 receptor monoclonal antibody, is used to treat rheumatic diseases. There is limited information about the administration of TCZ during lactation. The dried spot method, a simple technique for processing biological samples which involves placement of a drop of specimen onto filter paper, has been used in clinical pharmacology to determine various drug concentrations. This study examined the feasibility of sample collection using the dried milk spot (DMS) method for obtaining data about the transfer of TCZ into breast milk.
Concentrations of TCZ determined using DMSs prepared by patients were compared with those using liquid breast milk.
In an enzyme-linked immunosorbent assay of TCZ in DMSs, the accuracy ranged from 93.0% to 113.8% and the precision ranged from 0.3% to 8.4%. All concentrations of TCZ were within 15% of the reference value when analyzed on separate days. TCZ in DMSs at room temperature, 4°C, and -20°C were stable for 28 days. Extracted TCZ concentrations from patient-prepared DMSs were strongly correlated with those of liquid samples (r = 0.996). In a pharmacokinetic study, the median (range) maximum and minimum concentrations were 113 ng/mL (68-205) and 8.5 ng/mL (4.8-13.4), respectively. The milk-to-serum ratio at the trough TCZ concentration of 3 lactating mothers were 0.0015, 0.00082 and 0.0014.
The DMS method for measuring TCZ transfer into breast milk may be reliable and feasible, and should contribute to evaluating the safety of breast-fed infants whose mothers receive TCZ during lactation.
托珠单抗（TCZ）是一种人源化抗白细胞介素-6 受体单克隆抗体，用于治疗风湿性疾病。关于 TCZ 在哺乳期的使用，信息有限。干血斑法是一种简单的处理生物样本的技术，涉及将标本滴在滤纸上，已在临床药理学中用于确定各种药物浓度。本研究通过干奶斑（DMS）法采集样本，探讨了获取 TCZ 转移至母乳数据的可行性。
比较了患者制备的 DMS 与母乳中 TCZ 的浓度。
在 DMS 中 TCZ 的酶联免疫吸附测定中，准确度在 93.0%至 113.8%之间，精密度在 0.3%至 8.4%之间。当在不同日期分析时，所有 TCZ 浓度均在参考值的 15%以内。室温、4°C 和-20°C 下的 DMS 中 TCZ 稳定 28 天。由患者制备的 DMS 中提取的 TCZ 浓度与液体样本的浓度高度相关（r=0.996）。在一项药代动力学研究中，中位（范围）最大和最小浓度分别为 113ng/mL（68-205）和 8.5ng/mL（4.8-13.4）。3 位哺乳期母亲的 TCZ 浓度谷值时的乳汁-血清比值分别为 0.0015、0.00082 和 0.0014。
用于测量 TCZ 转移至母乳的 DMS 方法可能是可靠且可行的，有助于评估哺乳期接受 TCZ 治疗的母亲所喂养婴儿的安全性。
