Department of Pharmacy, University of Fukui Hospital, 23-3 Shimoaizuki, Matsuoka, Eiheiji, Fukui, 910-1193, Japan.
Department of Health and Nutrition, Faculty of Human Life Studies, Jin-ai University, 3-1-1 Ohde-cho, Echizen, Fukui, 915-8586, Japan.
Cancer Chemother Pharmacol. 2021 Apr;87(4):501-511. doi: 10.1007/s00280-020-04220-y. Epub 2021 Jan 8.
Vincristine (VCR) is a key drug for treating various malignancies. However, few data are available on the pharmacokinetics of VCR, especially in adult patients. The objective of this study was to clarify the population pharmacokinetics and exposure-response relationships of VCR in adult malignant lymphoma patients.
Blood samples were collected from patients who were administered R-CHOP-like regimens, and the VCR plasma concentration was determined using liquid chromatography-mass spectrometry. Using NONMEM software, population pharmacokinetic parameters were estimated, and covariates were evaluated. The relationships between the individual parameters and adverse events or therapeutic effects were also investigated.
Plasma concentrations were measured in 30 patients. In the final population pharmacokinetics model, body surface area and age were incorporated into clearance as significant covariates. The inter-individual variations in clearance and volume of distribution in the central and third compartments were 17.0, 26.6, and 66.3%, respectively, and the residual variability in the plasma concentration was 23.8%. Although the variability observed in the volume of distribution was large, good predictability was obtained in the individual estimation. The severity of anemia and peripheral neuropathy was correlated with clearance and peak concentration, respectively (adjusted P = 0.040 and 0.024, respectively). In diffuse large B cell lymphoma patients, those with higher area under the curve and dose experienced longer progression-free survival (P = 0.023 and 0.013, respectively).
The population pharmacokinetics of VCR were evaluated in adult malignant lymphoma patients. VCR pharmacokinetic data could explain in part the adverse events and prognosis of these patients.
长春新碱（VCR）是治疗各种恶性肿瘤的关键药物。然而，关于 VCR 的药代动力学数据，尤其是在成年患者中，数据很少。本研究的目的是阐明成人恶性淋巴瘤患者 VCR 的群体药代动力学和暴露-反应关系。
采集接受 R-CHOP 样方案治疗的患者的血样，并使用液相色谱-质谱法测定 VCR 血浆浓度。使用 NONMEM 软件估算群体药代动力学参数，并评估协变量。还研究了个体参数与不良事件或治疗效果之间的关系。
在 30 名患者中测量了血浆浓度。在最终的群体药代动力学模型中，体表面积和年龄被纳入清除率作为重要协变量。清除率和中央及第三隔室分布容积的个体间变异分别为 17.0%、26.6%和 66.3%，血浆浓度的残留变异为 23.8%。虽然观察到的分布容积变异性较大，但在个体估计中仍获得了良好的预测能力。贫血和周围神经病变的严重程度分别与清除率和峰浓度相关（调整 P 值分别为 0.040 和 0.024）。在弥漫性大 B 细胞淋巴瘤患者中，AUC 和剂量较高的患者无进展生存期更长（P 值分别为 0.023 和 0.013）。
评估了成人恶性淋巴瘤患者 VCR 的群体药代动力学。VCR 药代动力学数据部分解释了这些患者的不良事件和预后。
