Kondo A, Maeta M, Oka A, Tsujitani S, Ikeguchi M, Kaibara N
First Department of Surgery, Faculty of Medicine, Tottori University, Yonago, Japan.
Br J Cancer. 1996 May;73(10):1166-70. doi: 10.1038/bjc.1996.225.
The intraperitoneal (i.p.) administration of cisplatin (CDDP) is one of the most effective therapies for cancers that are confined to the abdominal cavity. However, the effect of fluid osmolarity on the therapeutic efficacy of i.p. administration of CDDP has not been well established. In the current study, hypotonic (154 mosmol 1-1), isotonic (308 mosmol 1-1) and hypertonic (616 mosmol 1-1) solutions of CDDP were prepared for an evaluation of their therapeutic efficacy in an experimental system. After i.p. administration, uptake of CDDP in vivo by tumor cells in hypotonic solution was significantly greater than in isotonic or hypertonic solution. The 50% lethal dose (LD50) value of CDDP in hypotonic solution (12.1 mg kg(-1)) was lower than that in isotonic solution (16.9 mg kg(-1)) and than that in hypertonic solution (28.6 mg kg(-1)). However, when a dose equal to one-half of the LD50 was administered in each solution to mice with i.p. tumours, survival of mice given the CDDP in hypotonic solution was significantly prolonged as compared with the survival of the other mice. These results demonstrate that the therapeutic efficacy of i.p. CDDP in mice is augmented when the drug is administered in hypotonic solution.
腹腔内注射顺铂（CDDP）是治疗局限于腹腔内癌症的最有效疗法之一。然而，液体渗透压对腹腔内注射CDDP治疗效果的影响尚未完全明确。在本研究中，制备了低渗（154 mosmol 1-1）、等渗（308 mosmol 1-1）和高渗（616 mosmol 1-1）的CDDP溶液，以评估它们在实验系统中的治疗效果。腹腔注射后，低渗溶液中肿瘤细胞对CDDP的体内摄取显著高于等渗或高渗溶液。低渗溶液中CDDP的50%致死剂量（LD50）值（12.1 mg kg(-1)）低于等渗溶液（16.9 mg kg(-1)）和高渗溶液（28.6 mg kg(-1)）。然而，当给患有腹腔肿瘤的小鼠在每种溶液中注射相当于LD50一半的剂量时，与其他小鼠相比，接受低渗溶液中CDDP的小鼠存活时间显著延长。这些结果表明，当药物在低渗溶液中给药时，腹腔内注射CDDP对小鼠的治疗效果会增强。
