YANG Dihong, XU Gaoqi, YANG Yiting, DING Haiying, ZHONG Like, ZHU Junfeng, MI Xiufang, XIN Wenxiu, WANG Jiaqi, FANG Luo. Exposure-Toxicity Analysis of Total and Unbound Paclitaxel of Nab-paclitaxel in Patients with Metastatic Breast Cancer[J]. Chinese Journal of Modern Applied Pharmacy. DOI: 10.13748/j.cnki.issn1007-7693.20242011
    Citation: YANG Dihong, XU Gaoqi, YANG Yiting, DING Haiying, ZHONG Like, ZHU Junfeng, MI Xiufang, XIN Wenxiu, WANG Jiaqi, FANG Luo. Exposure-Toxicity Analysis of Total and Unbound Paclitaxel of Nab-paclitaxel in Patients with Metastatic Breast Cancer[J]. Chinese Journal of Modern Applied Pharmacy. DOI: 10.13748/j.cnki.issn1007-7693.20242011

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

    • 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 Cmax of total and unbound paclitaxel were (13100±2710) ng·mL−1 and (677±310) ng·mL−1, the AUC0-∞ 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 AUC0-∞ of total and unbound paclitaxel (total paclitaxel: r=0.37, P<0.01; unbound paclitaxel: r=0.38, P<0.01). The AUC0-∞ 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 (AUC0-∞) were significantly correlated with decrease in neutrophil counts.
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