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

Sandor Kerpel-Fronius, Jaap Verwey, Miquel Stuurman, B. Kanyár, Peter Lelieveld, Herbert M. Pinedo

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)104-108
Number of pages5
JournalCancer Chemotherapy and Pharmacology
Volume22
Issue number2
DOIs
StatePublished - Aug 1988
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Oncology
  • Cancer Research

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