Tamura Takashi, Imai Jun, Matsumoto Akihiro, Tanimoto Masahiko, Suzuki Akira, Horikiri Yuji, Suzuki Takehiko, Yoshino Hiroyuki, Ike Osamu
DDS Research Department, Discovery Research Laboratory, Tanabe Seiyaku Co. Ltd., 3-16-89 Kashima, Yodogawa-ku, Osaka 532-8505, Japan.
Eur J Pharm Biopharm. 2002 Jul;54(1):1-7. doi: 10.1016/s0939-6411(02)00037-1.
The aim of this study was to clarify the organ distribution of cisplatin (CDDP) after intraperitoneal (i.p.) administration of cisplatin-loaded microspheres (CDDP-MS). The distribution of CDDP to normal organs lying in the peritoneal cavity after i.p. administration of CDDP-MS was assessed by comparing with subcutaneous administration to non-cancerous mice. The organ distribution of CDDP after i.p. administration of CDDP-MS shows that CDDP released from microspheres was distributed to the organs lying in the peritoneal cavity and in the retroperitoneum. These are mainly from the systemic circulation, but are not directly from the organ surface. The distribution of CDDP to tumors was evaluated in sarcoma180 tumor-bearing mice by comparing with a bolus injection. The CDDP-MS delivered CDDP to tumors more effectively than did bolus injection. The distribution of CDDP-MS in the peritoneal cavity was in accord with the tumor distribution. This concordance and sustained exposure of CDDP to the tumors might play a critical role in enhancing the CDDP accumulation in tumors. It is concluded that CDDP-MS have a distinct regional pharmacokinetic advantage for peritoneal carcinomatosis, and that i.p. administration of CDDP-MS is an effective treatment for peritoneal carcinomatosis.
本研究的目的是阐明腹腔内(i.p.)给予顺铂微球(CDDP-MS)后顺铂(CDDP)的器官分布情况。通过与皮下给药于非癌小鼠进行比较,评估腹腔内给予CDDP-MS后CDDP在位于腹腔内的正常器官中的分布。腹腔内给予CDDP-MS后CDDP的器官分布表明,从微球释放的CDDP分布到位于腹腔和腹膜后的器官中。这些主要来自体循环,但并非直接来自器官表面。通过与大剂量注射进行比较,评估了CDDP-MS在荷肉瘤180肿瘤小鼠中对肿瘤的分布情况。CDDP-MS比大剂量注射更有效地将CDDP递送至肿瘤。CDDP-MS在腹腔内的分布与肿瘤分布一致。这种一致性以及CDDP对肿瘤的持续暴露可能在增强CDDP在肿瘤中的蓄积方面发挥关键作用。得出的结论是,CDDP-MS对腹膜癌有明显的区域药代动力学优势,并且腹腔内给予CDDP-MS是治疗腹膜癌的有效方法。