注射用紫杉醇(白蛋白结合型)在转移性乳腺癌患者中的暴露水平与中性粒细胞计数减少的相关性分析

杨迪虹; 许高奇; 杨逸婷; 丁海樱; 钟里科; 朱俊峰; 米秀芳; 辛文秀; 汪佳琪; 方罗

doi:10.13748/j.cnki.issn1007-7693.20242011

注射用紫杉醇(白蛋白结合型)在转移性乳腺癌患者中的暴露水平与中性粒细胞计数减少的相关性分析

Exposure-Toxicity Analysis of Total and Unbound Paclitaxel of Nab-paclitaxel in Patients with Metastatic Breast Cancer

摘要

摘要:
目的研究注射用紫杉醇(白蛋白结合型)在转移性乳腺癌患者体内总紫杉醇和游离紫杉醇的药动学(pharmacokinetics，PK)参数及其与中性粒细胞计数减少的相关性。
方法纳入60例转移性乳腺癌患者接受注射用紫杉醇(白蛋白结合型)后总紫杉醇和游离紫杉醇的系列浓度，采用R软件的“PKNCA”包计算PK参数，以线性回归模型分别分析血浆总紫杉醇和游离紫杉醇暴露量与患者中性粒细胞计数减少的相关性，“pROC”包绘制受试者工作特征(ROC)曲线，探索严重中性粒细胞计数降低风险的药物阈值暴露量。
结果血浆总紫杉醇和游离紫杉醇的C_max分别为(13100±2710) ng·mL⁻¹和(677±310) ng·mL⁻¹，AUC_0-∞分别为(13600±3430) ng·h·mL⁻¹和(526±278) ng·h·mL⁻¹，游离分数为(6.00±3.30)%。血浆总紫杉醇和游离紫杉醇的AUC_0-∞与中性粒细胞计数减少百分比均有显著相关性(总紫杉醇：r=0.37，P<0.01；游离紫杉醇：r=0.38，P<0.01)，血浆总紫杉醇和游离紫杉醇AUC_0-∞分别>14697.50、646.16 ng·h·mL⁻¹时，严重中性粒细胞计数降低的风险升高。
结论注射用紫杉醇(白蛋白结合型)的血浆总紫杉醇和游离紫杉醇的暴露(AUC_0-∞)均与转移性乳腺癌患者中性粒细胞计数减少显著相关。

Abstract:
OBJECTIVE To study the pharmacokinetics(PK) parameters of total and unbound paclitaxel after administration of albumin-bound paclitaxel (nab-paclitaxel), and the relationship between exposure of total or unbound paclitaxel and neutropenia in patients with metastatic breast cancer.
METHODS Concentrations of total and unbound paclitacel were collected from 60 patients with metastatic breast cancer who who received nab-paclitaxel in this study. The "PKNCA" package was used to calculate PK parameters in R software. The correlation between total or unbound paclitaxel exposure and decrease in neutrophil counts was analyzed by linear regression models. The "pROC" package was used to draw receiver operating characteristic (ROC) curve in order to screen the threshold of the risk of severe neutropenia.
RESULTS The C_max of total and unbound paclitaxel were (13100±2710) ng·mL⁻¹ and (677±310) ng·mL⁻¹, the AUC_0-∞ were (13600±3430) ng·h·mL⁻¹ and (526±278) ng·h·mL⁻¹, respectively, with free fraction of (6.00±3.30)%. The reduction in neutrophil counts was significantly correlated with AUC_0-∞ of total and unbound paclitaxel (total paclitaxel: r=0.37, P<0.01; unbound paclitaxel: r=0.38, P<0.01). The AUC_0-∞ of total paclitaxel exceeding 14697.50 ng·h·mL⁻¹ or 646.16 ng·h·mL⁻¹ for unbound paclitaxel increasing the risk of grade ≥Ⅲ neutropenia.
CONCLUSION Both total and unbound paclitaxel exposure (AUC_0-∞) were significantly correlated with decrease in neutrophil counts.

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