Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, Tokyo, Japan.
Department of Clinical Pharmacy, Oita University Hospital, Yufu, Oita, Japan.
Pharmacol Res Perspect. 2024 Aug;12(4):e1255. doi: 10.1002/prp2.1255.
In this study, plasma belimumab concentrations were measured over the course of treatment in systemic lupus erythematosus (SLE) patients on belimumab therapy, and intra- and interindividual variations in plasma belimumab concentration were evaluated. A single-center prospective study was conducted at Oita University Hospital to evaluate trough plasma concentrations over the course of treatment in 13 SLE patients treated with intravenous belimumab. Plasma belimumab concentrations were measured by a validated ultra-high performance liquid chromatography with tandem mass spectrometry method. The median age of the patients was 40 (interquartile range: 35-51) years and the median weight was 51.8 (47.0-58.1) kg. A mean of 9.4 (range: 1-13) blood samples was collected per patient at routine visits. The mean (± SD) plasma belimumab concentration was 33.4 ± 11.9 μg/mL in the patient with the lowest concentration and 170.0 ± 16.6 μg/mL in the patient with the highest concentration, indicating a 5-fold difference between patients. On the other hand, the within-patient coefficient of variation ranged from 7.1% to 35.7%, showing no large variations. No significant correlation was observed between plasma belimumab concentration and belimumab dose (mg/kg) (Spearman's rank correlation coefficient = 0.22, p = .54). Examinations of trough plasma belimumab concentrations over the course of treatment in patients with SLE showed small intraindividual variation but large interindividual variation. Plasma belimumab trough concentration varied widely among patients administered the approved dose.
在这项研究中，评估了系统性红斑狼疮 (SLE) 患者接受贝利尤单抗治疗过程中的血浆贝利尤单抗浓度，并评估了血浆贝利尤单抗浓度的个体内和个体间差异。在大分大学医院进行了一项单中心前瞻性研究，以评估 13 名接受静脉注射贝利尤单抗治疗的 SLE 患者治疗过程中的谷浓度。通过验证的超高效液相色谱-串联质谱法测量血浆贝利尤单抗浓度。患者的中位年龄为 40 岁（四分位距：35-51 岁），中位体重为 51.8 公斤（47.0-58.1 公斤）。每位患者在常规就诊时平均采集 9.4 份（范围：1-13）血样。最低浓度患者的平均（± SD）血浆贝利尤单抗浓度为 33.4 ± 11.9 μg/mL，最高浓度患者为 170.0 ± 16.6 μg/mL，表明患者之间相差 5 倍。另一方面，个体内变异系数范围为 7.1%至 35.7%，无较大变异。未观察到血浆贝利尤单抗浓度与贝利尤单抗剂量（mg/kg）之间存在显著相关性（Spearman 等级相关系数=0.22，p=0.54）。对 SLE 患者治疗过程中的谷血浆贝利尤单抗浓度进行检查显示，个体内变异较小，但个体间变异较大。给予批准剂量的患者中，血浆贝利尤单抗谷浓度差异很大。
