Department of Pharmacy and Pharmacology, Antoni van Leeuwenhoek/Netherlands Cancer Institute, Amsterdam, The Netherlands.
Department of Development and Regeneration, Obstetrics and Gynaecology, KU Leuven, Leuven, Belgium.
Clin Pharmacokinet. 2021 Jun;60(6):775-784. doi: 10.1007/s40262-020-00961-4. Epub 2021 Jan 28.
Based on reassuring short-term foetal and maternal safety data, there is an increasing trend to administer chemotherapy during the second and third trimesters of pregnancy. The pharmacokinetics (PK) of drugs might change as a result of several physiological changes that occur during pregnancy, potentially affecting the efficacy and safety of chemotherapy.
With this analysis, we aimed to quantitatively describe the changes in the PK of docetaxel, paclitaxel, doxorubicin and epirubicin in pregnant women compared with non-pregnant women.
PK data from 9, 20, 22 and 16 pregnant cancer patients from the International Network of Cancer, Infertility and Pregnancy (INCIP) were available for docetaxel, paclitaxel, doxorubicin and epirubicin, respectively. These samples were combined with available PK data from non-pregnant patients. Empirical non-linear mixed-effects models were developed, evaluating fixed pregnancy effects and gestational age as covariates.
Overall, 82, 189, 271, and 227 plasma samples were collected from pregnant patients treated with docetaxel, paclitaxel, doxorubicin and epirubicin, respectively. The plasma PK data were adequately described by the respective models for all cytotoxic drugs. Typical increases in central and peripheral volumes of distribution of pregnant women were identified for docetaxel, paclitaxel, doxorubicin and epirubicin. Additionally, docetaxel, doxorubicin and paclitaxel clearance were increased in pregnant patients, resulting in lower exposure in pregnant women compared with non-pregnant patients.
Given the interpatient variability, the identified pregnancy-induced changes in PK do not directly warrant dose adjustments for the studied drugs. Nevertheless, these results underscore the need to investigate the efficacy of chemotherapy, when administered during pregnancy.
基于令人安心的短期胎儿和母体安全性数据，越来越多的趋势是在妊娠第二和第三 trimester 期间给予化疗。由于怀孕期间发生的几种生理变化，药物的药代动力学（PK）可能会发生变化，从而可能影响化疗的疗效和安全性。
通过这项分析，我们旨在定量描述与非妊娠妇女相比，妊娠妇女多西紫杉醇、紫杉醇、阿霉素和表阿霉素 PK 的变化。
国际癌症、不孕和妊娠网络（INCIP）的 9、20、22 和 16 名妊娠癌症患者的 PK 数据分别可用于多西紫杉醇、紫杉醇、阿霉素和表阿霉素。将这些样本与非妊娠患者的可用 PK 数据合并。开发了经验性非线性混合效应模型，评估固定妊娠效应和妊娠年龄作为协变量。
总体而言，分别接受多西紫杉醇、紫杉醇、阿霉素和表阿霉素治疗的妊娠患者共采集了 82、189、271 和 227 个血浆样本。所有细胞毒性药物的血浆 PK 数据均由各自的模型充分描述。确定了多西紫杉醇、紫杉醇、阿霉素和表阿霉素的中央和外周分布体积的典型增加。此外，多西紫杉醇、阿霉素和紫杉醇在妊娠患者中的清除率增加，导致妊娠妇女的暴露水平低于非妊娠妇女。
鉴于个体间的差异，PK 中确定的妊娠诱导变化并不直接需要调整所研究药物的剂量。然而，这些结果强调了在怀孕期间进行化疗时需要调查其疗效的必要性。
