Institute of Traditional Medicine, School of Medicine, National Yang-Ming University Taipei, Taiwan ; Department of Education and Research, Taipei City Hospital Taipei, Taiwan.
Institute of Traditional Medicine, School of Medicine, National Yang-Ming University Taipei, Taiwan ; Department of Radiation Oncology, Mackay Memorial Hospital Taipei, Taiwan ; Department of Medical Research, Mackay Memorial Hospital Taipei, Taiwan.
Am J Transl Res. 2015 Feb 15;7(2):375-84. eCollection 2015.
Cisplatin (CDDP) is employed to enhance radiotherapy's (RT) effect for various cancers. However, the effects of local RT on chemotherapeutics in the plasma and lymphatic system remain unclear. Here, we evaluated the influence of pelvic irradiation on the pharmacokinetics (PK) of CDDP using rats as an experimental model.
RT with 2 Gy and 0.5 Gy were delivered to the whole pelvis of Sprague-Dawley rats. CDDP at 5 mg/kg and 10 mg/kg was intravenously infused 24 hours after radiation for the plasma and lymphatic system, respectively. The pharmacokinetics of CDDP in the plasma and lymphatic system were calculated.
Compared with sham-irradiated controls, the whole pelvic irradiation increased the area under the concentration versus time curve (AUC) of CDDP (5 mg/kg) in the plasma by 80% at 0.5 Gy and 87% at 2 Gy, respectively. In contrast, the AUC of CDDP decreased in bile by 13% at both dose levels. Intriguingly, RT could also increase the AUC of CDDP (10 mg/kg) in the lymphatic fluid by 87% at 2 Gy. In addition, the AUC in CDDP without and with RT was 2.8-fold and 3.4-fold greater for the lymph system than for the plasma, respectively.
A local pelvic RT could modulate the systemic PK of CDDP in both the plasma and lymphatic fluids of the rats. The RT-PK phenomena are worth further investigation.
顺铂（CDDP）被用于提高各种癌症的放射治疗（RT）效果。然而，局部 RT 对血浆和淋巴系统中化疗药物的影响尚不清楚。在这里，我们使用大鼠作为实验模型评估了骨盆照射对 CDDP 药代动力学（PK）的影响。
对 Sprague-Dawley 大鼠进行全骨盆 2 Gy 和 0.5 Gy 的 RT。在照射后 24 小时，分别向血浆和淋巴系统静脉内输注 5 mg/kg 和 10 mg/kg 的 CDDP。计算 CDDP 在血浆和淋巴系统中的药代动力学。
与假照射对照组相比，全骨盆照射使血浆中 CDDP（5 mg/kg）的曲线下面积（AUC）分别在 0.5 Gy 和 2 Gy 时增加了 80%和 87%。相比之下，在两个剂量水平下，胆汁中的 CDDP AUC 减少了 13%。有趣的是，RT 还可以使 2 Gy 时淋巴液中 CDDP（10 mg/kg）的 AUC 增加 87%。此外，RT 前后 CDDP 在 AUC 中分别是血浆的 2.8 倍和 3.4 倍。
局部骨盆 RT 可以调节大鼠血浆和淋巴液中 CDDP 的全身 PK。RT-PK 现象值得进一步研究。
