Long-term disposition of a novel lipophilic platinum complex SM-11355 in dog after intrahepatic arterial administration: highly sensitive detection of platinum and radioactivity.
1. The disposition of SM-11355, an anticancer platinum complex for hepatocellular carcinoma, was investigated in dog by measuring platinum (Pt) and radioactivity levels following intrahepatic arterial administration of (14)C-SM-11355 suspended in Lipiodol, an oily lymphographic agent. Plasma and excretion profiles were monitored in six animals, with tissue distribution studied after 1 day, 4 and 13 weeks (n = 2/time point). 2. SM-11355 was released very slowly into the systemic circulation from Lipiodol, resulting in very low levels of Pt compounds in plasma, urine, faeces and organs. Plasma levels of Pt and radioactivity declined with apparent half-lives of 5-7 weeks. Excretion continued even at 3 months after the administration with proportions excreted for Pt and radioactivity up to 30-60% in urine and 8-10% in faeces. 3. The Pt and radioactivity in the liver accounted for 80-100% of the dose at 1 day and for 20-50% at 13 weeks after the administration, predominately as intact SM-11355. The concentrations were highest in the left lobe of the liver, the administration site, but levels in the remainder of the liver were also markedly higher than those in plasma and other tissues. 4. The results strongly support the concept that SM-11355 targets the liver with highly selectivity and sustained release of Pt compounds.
Shimakura
J
J
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd, 1-98 Kasugade-naka 3-chome, Konohana-ku, Osaka, 554-8558, Japan. shimakura@sc.sumitomo-chem.co.jp
Fujimoto
K
K
Komuro
S
S
Nakano
M
M
Kanamaru
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes; D004285:Dogs; D006499:Hepatic Artery; D007261:Infusions, Intra-Arterial; D007459:Iodized Oil / Q000008:administration & dosage; D008099:Liver / Q000378:metabolism; D008297:Male; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010984:Platinum / Q000097:blood / Q000493:pharmacokinetics; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D009944:Organoplatinum Compounds; D010984:Platinum; C406530:miriplatin; D007459:Iodized Oil