[Studies on the physiological disposition and pharmacokinetics of 7-N-(p-hydroxyphenyl)-mitomycin C]. 1982

S Okumura, and T Deguchi, and N Nakamizo

A new mitomycin derivative, 7-N-(p-hydroxyphenyl)-mitomycin C (KW 2083), was labeled with 14C at 3 and 5 position of p-hydroxyphenyl moiety. Its radioactive purity and specific radioactivity were 97.6% and 3.42 mu Ci/mg, respectively. The labeled drug was administered intravenously to male rats or pregnant rats. Radioactivity was rapidly cleared from the plasma and transferred to the peripheral tissues. However low and sustained level of radioactivity was maintained in the plasma, even 48 to 72 hours after administration. About 29% of the radioactivity was recovered from the urine and 58% from the feces by 72 hours after administration. In the bile, 45% of the dose was excreted until 48 hours after administration, and the enterohepatic circulation was observed. The tissue levels of 14C-KW 2083 given to male rats were highest in the kidney, liver and intestinal contents. In the brain, eyes and spinal cord the radioactivity was very low. Autoradiography with 14C-KW 2083 in male or pregnant rats demonstrated that radioactivity distributed in kidney, liver and intestinal contents. The transfer of radioactivity was very low in the fetuses of rats. Radioactivity was observed to some extent in the fetal membrane. Plasma concentrations of KW 2083 or mitomycin C in dogs were determined by means of bioactivity and could be best described by a two-compartment open model. The total clearance of KW 2083 was higher than mitomycin C and hence the biological half life of KW 2083 was shorter. The result may suggest less toxicity of KW 2083 to the host cells.

UI MeSH Term Description Entries
D007275 Injections, Intravenous Injections made into a vein for therapeutic or experimental purposes. Intravenous Injections,Injection, Intravenous,Intravenous Injection
D007408 Intestinal Absorption Uptake of substances through the lining of the INTESTINES. Absorption, Intestinal
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D008431 Maternal-Fetal Exchange Exchange of substances between the maternal blood and the fetal blood at the PLACENTA via PLACENTAL CIRCULATION. The placental barrier excludes microbial or viral transmission. Transplacental Exposure,Exchange, Maternal-Fetal,Exposure, Transplacental,Maternal Fetal Exchange
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.
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D002250 Carbon Radioisotopes Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes. Radioisotopes, Carbon
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog

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