Pharmacokinetics of miriplatin in experimental dog models of hepatic or renal impairment
| Autor: | Setsuko Komuro, Jin Shimakura, Toshifumi Fukuoka, Atsushi Kitamura, Masashi Yabuki, Hiroyuki Asano, Minoru Nakano |
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| Rok vydání: | 2011 |
| Předmět: |
Male
food.ingredient Organoplatinum Compounds Clinical chemistry medicine.medical_treatment Antineoplastic Agents Urine Poppy seed Pharmacology Liver Cirrhosis Experimental chemistry.chemical_compound food Dogs Pharmacokinetics medicine Distribution (pharmacology) Animals Pharmacology (medical) Renal Insufficiency business.industry Nephrectomy chemistry Liver Miriplatin Thioacetamide business |
| Zdroj: | European journal of drug metabolism and pharmacokinetics. 36(4) |
| ISSN: | 0378-7966 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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