Organ distribution of cisplatin after intraperitoneal administration of cisplatin-loaded microspheres.
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.
Tamura
Takashi
T
DDS Research Department, Discovery Research Laboratory, Tanabe Seiyaku Co. Ltd., 3-16-89 Kashima, Yodogawa-ku, Osaka 532-8505, Japan. t-tamura@tanabe.co.jp
Imai
Jun
J
Matsumoto
Akihiro
A
Tanimoto
Masahiko
M
Suzuki
Akira
A
Horikiri
Yuji
Y
Suzuki
Takehiko
T
Yoshino
Hiroyuki
H
Ike
Osamu
O
D000818:Animals; D019540:Area Under Curve; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D008863:Microspheres; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D002945:Cisplatin