title: Pharmacokinetics of miriplatin in experimental dog models of hepatic or renal impairment.
abstract: Miriplatin is an anticancer platinum complex for treatment of hepatocellular carcinomas by intra-hepatic arterial injection suspended in an iodinated ethyl ester of fatty acids from poppy seed oil as a carrier. Effects of liver and kidney function on( 14)C-miriplatin pharmacokinetics were assessed using dog models of hepatic and renal impairment introduced by thioacetamide exposure and 7/8 nephrectomy, respectively. Miriplatin was selectively delivered to the liver; platinum and radioactive component were gradually released into systemic circulation and excreted into urine. Microautoradiographic analysis of liver specimens showed( 14)C-miriplatin to be localized in blood vessels and/or macrophage-like cells. These features of miriplatin disposition were not affected by hepatic impairment. Thus, in clinical settings, hepatic impairment would not be expected to affect the intra-hepatic distribution and systemic pharmacokinetics of miriplatin. In dogs with renal impairment, although inconclusive, plasma concentrations of ultrafilterable platinum and radioactivity increased due to reduction in renal clearance.
authors: Pharmacokinetics Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan.
authors: Atsushi
authors: A
authors: Kitamura
authors: Jin
authors: J
authors: Shimakura
authors: Masashi
authors: M
authors: Yabuki
authors: Hiroyuki
authors: H
authors: Asano
authors: Toshifumi
authors: T
authors: Fukuoka
authors: Minoru
authors: M
authors: Nakano
authors: Setsuko
authors: S
authors: Komuro
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D004285:Dogs; D008099:Liver / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008297:Male; D009944:Organoplatinum Compounds / Q000493:pharmacokinetics*; D051437:Renal Insufficiency / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C406530:miriplatin