BIOMAT Database Logo BIOMAT Database Logo

Pharmacokinetics and toxicity of mitomycin C in rodents, given alone, in combination, or after induction of microsomal drug metabolism. 1988

S Kerpel-Fronius, and J Verwey, and M Stuurman, and B Kanyár, and P Lelieveld, and H M Pinedo
Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands.

The pharmacokinetics of mitomycin (MMC) was studied in Wistar rats. Up to five half-lives, the plasma concentration-time curve was biphasic. The AUC changed linearly with increasing doses between 0.5 and 7.5 mg/kg, which corresponds to 0.2 and 3 times the LD50 value in rats. Most of the drug was metabolized, and only 1%-2% and 10%-15% of the dose was eliminated unchanged by biliary and urinary excretion, respectively. The AUC of MMC at the LD50 is slightly less than that reported for the human MTD. Inoculation of MMC together with 5-fluorouracil and doxorubicin did not change the terminal half-life of MMC but decreased the total body clearance and the volume of distribution. The lack of significant influence of phenobarbital and 3-methylcholanthrene pretreatment on the terminal elimination half-life suggests that microsomal drug-metabolizing enzymes inducible by these compounds do not play a decisive role in the in vivo biotransformation of MMC.

UI MeSH Term Description Entries
D008297 Male Males
D008748 Methylcholanthrene A carcinogen that is often used in experimental cancer studies. 20-Methylcholanthrene,3-Methylcholanthrene,20 Methylcholanthrene,3 Methylcholanthrene
D008862 Microsomes, Liver Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough. Liver Microsomes,Liver Microsome,Microsome, Liver
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.
D010634 Phenobarbital A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. Phenemal,Phenobarbitone,Phenylbarbital,Gardenal,Hysteps,Luminal,Phenobarbital Sodium,Phenobarbital, Monosodium Salt,Phenylethylbarbituric Acid,Acid, Phenylethylbarbituric,Monosodium Salt Phenobarbital,Sodium, Phenobarbital
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
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
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
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

Related Publications

S Kerpel-Fronius, and J Verwey, and M Stuurman, and B Kanyár, and P Lelieveld, and H M Pinedo
Pharmacokinetics of mitomycin C in patients receiving the drug alone or in combination.
September 1983, Cancer treatment reports,
S Kerpel-Fronius, and J Verwey, and M Stuurman, and B Kanyár, and P Lelieveld, and H M Pinedo
Mitomycin C toxicity and pharmacokinetics in mice given sulfur nucleophiles.
January 1988, Anticancer research,
S Kerpel-Fronius, and J Verwey, and M Stuurman, and B Kanyár, and P Lelieveld, and H M Pinedo
In vivo toxicity of foscarnet and zidovudine given alone or in combination.
August 1996, Toxicology and applied pharmacology,
S Kerpel-Fronius, and J Verwey, and M Stuurman, and B Kanyár, and P Lelieveld, and H M Pinedo
The difference in pharmacokinetics of mitomycin C, given either as a single agent or as a part of combination chemotherapy.
January 1986, Journal of cancer research and clinical oncology,
S Kerpel-Fronius, and J Verwey, and M Stuurman, and B Kanyár, and P Lelieveld, and H M Pinedo
Experimental treatment of cancer with mitomycin C alone or in combination with carzinophilin.
September 1961, The Journal of antibiotics,
S Kerpel-Fronius, and J Verwey, and M Stuurman, and B Kanyár, and P Lelieveld, and H M Pinedo
Single-dose pharmacokinetics of modafinil and methylphenidate given alone or in combination in healthy male volunteers.
March 1998, Journal of clinical pharmacology,
S Kerpel-Fronius, and J Verwey, and M Stuurman, and B Kanyár, and P Lelieveld, and H M Pinedo
Steady-state pharmacokinetics and tolerability of modafinil given alone or in combination with methylphenidate in healthy volunteers.
August 2001, Journal of clinical pharmacology,
S Kerpel-Fronius, and J Verwey, and M Stuurman, and B Kanyár, and P Lelieveld, and H M Pinedo
Pharmacokinetics of ceftazidime given alone and combination with probenecid to unweaned calves.
September 1989, American journal of veterinary research,
S Kerpel-Fronius, and J Verwey, and M Stuurman, and B Kanyár, and P Lelieveld, and H M Pinedo
Pharmacokinetics of BW12C and mitomycin C, given in combination in a phase 1 study in patients with advanced gastrointestinal cancer.
January 1993, Cancer chemotherapy and pharmacology,
S Kerpel-Fronius, and J Verwey, and M Stuurman, and B Kanyár, and P Lelieveld, and H M Pinedo
Antiviral efficacy and toxicity of ribavirin and foscarnet each given alone or in combination in the murine AIDS model.
March 1997, Toxicology and applied pharmacology,
Copied contents to your clipboard!