Biomaterial Database

[Pharmacokinetics of mitomycin C and its derivative (KW-2083)]. 1982

H Fujita

Pharmacokinetics of MMC was studied by bioassay method in cancer patients and experimental animals, and they were compared with those of a new mitomycin derivative, KW-2083. The blood level of MMC decreased relative by rapidly, t 1/2 beta in iv dose of 30, 20 and 10 mg/body to man was 50, 41 and 33 minutes, respectively. The drug level was able to increase locally by employing perfusion, arterial infusion, hemi-upper body infusion and intra-cavitary injection. The tissue level of MMC was high in the lung, kidney, muscle and skin, and moderate in the tumor of S180 bearing mice. MMC was inactivated strongly in the homogenates of the liver and kidney, and moderately in the heart and intestine of human tissues. The inactivation was enhanced by the addition of NADPH, vitamin B6, glutathione, etc. The blood level of KW-2083 in patients and mice decreased more rapidly than MMC. T 1/2 beta of KW-2083 in patients after iv injection at 70, 40 and 20 mg/body was about 18 minutes. The tissue level of KW-2083 in S 180 bearing mice was the highest in the lung and skin, followed by the kidney and tumor. The elimination rate of the drug from each tissue was more rapid than that of MMC. KW-2083 was highly excreted into the bile and more highly inactivated in the homogenates of the liver, kidney, muscle, etc. as compared with MMC. These pharmacokinetic behaviours of KW-2083 might be related to the lower toxicity and higher therapeutic ratio in experimental animals.

UI	MeSH Term	Description	Entries
D007263	Infusions, Parenteral	The administration of liquid medication, nutrient, or other fluid through some other route than the alimentary canal, usually over minutes or hours, either by gravity flow or often by infusion pumping.	Intra-Abdominal Infusions,Intraperitoneal Infusions,Parenteral Infusions,Peritoneal Infusions,Infusion, Intra-Abdominal,Infusion, Intraperitoneal,Infusion, Parenteral,Infusion, Peritoneal,Infusions, Intra-Abdominal,Infusions, Intraperitoneal,Infusions, Peritoneal,Intra Abdominal Infusions,Intra-Abdominal Infusion,Intraperitoneal Infusion,Parenteral Infusion,Peritoneal Infusion
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008937	Mitomycins	A group of methylazirinopyrroloindolediones obtained from certain Streptomyces strains. They are very toxic antibiotics used as ANTINEOPLASTIC AGENTS in some solid tumors. PORFIROMYCIN and MITOMYCIN are the most useful members of the group.
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000903	Antibiotics, Antineoplastic	Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.	Antineoplastic Antibiotics,Cytotoxic Antibiotics,Antibiotics, Cytotoxic
D016685	Mitomycin	An antineoplastic antibiotic produced by Streptomyces caespitosus. It is one of the bi- or tri-functional ALKYLATING AGENTS causing cross-linking of DNA and inhibition of DNA synthesis.	Mitomycin C,Ametycine,Mitocin-C,Mitomycin-C,Mutamycin,NSC-26980,Mitocin C,MitocinC,NSC 26980,NSC26980
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus