Metabolic fate of ethyl O-[N-(p-carboxyphenyl)-carbamoyl] mycophenolate (CAM), a new antitumor agent, in experimental animals

Journal of Pharmacobio-dynamics
Y Matsuzawa, T Nakase


Absorption, distribution, metabolism and excretion of ethyl O-[N-(p-carboxyphenyl)-carbamoyl] mycophenolate (CAM), a new antitumor agent, was studied in mice using 14C-labeled CAM and species difference of metabolism was studied in mice, rats, guinea pigs, rabbits and dogs. CAM was rapidly absorbed from the gastrointestinal tract of mice. Concentration of radioactivity in the plasma of mice showed two peaks reflecting enterohepatic circulation of metabolites, the first was 30 min and the second was 6 h after dosing. Extremely high concentration of radioactivity was observed in the bile as about 100 times of the radioactivity detected in the plasma. Wide distribution of radioactivity was observed in the whole body tissues of the tumor-bearing mice. Strong radioactivity was presented in the liver, kidney, bile and gastrointestinal content. Radioactivity in the tumor was higher than those in the liver and kidney 24 h after dosing. About 45% of the dose and 30% of the dose were excreted in the urine and feces, respectively, during 24 h after administration of 14C-CAM to mice. The metabolites of CAM were only mycophenolic acid (MPA) and its glucuronic acid conjugate (MPA-G) in all tested animals. Converting ratio of MPA to MPA-G dif...Continue Reading


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Related Concepts

Ethyl O-(N-(4-carboxyphenyl)carbamoyl)mycophenolate, (E)-isomer
Antineoplastic Agents
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Canis familiaris
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Mouse, Inbred ICRC
Mycophenolic Acid

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