Saito Akira, Kimura Natsuka, Kaneda Yuji, Ohzawa Hideyuki, Miyato Hideyo, Yamaguchi Hironori, Lefor Alan Kawarai, Nagai Ryozo, Sata Naohiro, Kitayama Joji, Aizawa Kenichi
Department of Surgery, Jichi Medical University, Tochigi 329-0498, Japan.
Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Tochigi 329-0498, Japan.
Cancers (Basel). 2022 Aug 1;14(15):3753. doi: 10.3390/cancers14153753.
Gastrointestinal cancer with massive nodal metastases is a lethal disease. In this study, using a porcine model, we infused the anti-cancer drug Paclitaxel (PTX) into thoracic ducts to examine the efficiency of drug delivery to intra-abdominal lymph nodes. We established a technical method to catheterize the thoracic duct in the necks of pigs. We then compared the pharmacokinetics of PTX administered intrathoracically with those of systemic (intravenous) infusion. Serum, liver, and spleen concentrations of PTX were significantly lower following thoracic duct (IT) infusion than after intravenous (IV) administration approximately 1-8 h post-infusion. However, PTX levels in abdominal lymph nodes were maintained at relatively high levels up to 24 h after IT infusion compared to after IV infusion. Concentrations of PTX in urine were much higher after IT administration than after IV administration. After IT infusion, the same concentration of PTX was obtained in abdominal lymph nodes, but the serum concentration was lower than after systemic infusion. Therefore, IT infusion may be able to achieve higher PTX doses than IV infusion. IT delivery of anti-cancer drugs into the thoracic duct may yield clinical benefits for patients with extensive lymphatic metastases in abdominal malignancies.
伴有大量淋巴结转移的胃肠道癌是一种致命疾病。在本研究中，我们使用猪模型，将抗癌药物紫杉醇（PTX）注入胸导管，以检查药物输送至腹腔淋巴结的效率。我们建立了一种在猪颈部插入胸导管的技术方法。然后，我们比较了经胸腔内注入PTX与全身（静脉）输注的药代动力学。输注后约1 - 8小时，经胸导管（IT）输注后血清、肝脏和脾脏中的PTX浓度显著低于静脉（IV）给药后。然而，与静脉输注相比，经胸导管输注后24小时内腹腔淋巴结中的PTX水平维持在相对较高水平。经胸导管给药后尿液中PTX的浓度远高于静脉给药后。经胸导管输注后，腹腔淋巴结中获得了相同浓度的PTX，但血清浓度低于全身输注后。因此，经胸导管输注可能比静脉输注能够实现更高的PTX剂量。将抗癌药物经胸导管输送可能会给腹部恶性肿瘤伴有广泛淋巴转移的患者带来临床益处。
