Metabolism and pharmacokinetics of p-(3,3-dimethyl-1-triazeno) benzoic acid in M5076 sarcoma-bearing mice

Emilio Benfenati, Pierluigi Farina, Tina Colombo, Gianluca De Bellis, Mauro Valerio Capodiferro, Maurizio D'Incalci

Research output: Contribution to journalArticlepeer-review

Abstract

The pharmacokinetics of the anticancer agent p-(3,3-dimethyl-1-triazeno) benzoic acid (pCOOH-DMT), a drug now in phase I clinical trial in Europe, was investigated in C57 Bl female mice with M5076 reticulum-cell sarcoma that were treated i.v. with 200 mg/kg pCOOH-DMT. The drug disappeared from plasma with a terminal half-life of about 2.5 h. Plasma clearance was approximately 6 ml/min per kg. Distribution studies showed some differences in drug levels in different tissues. The highest levels were found in the tumor, liver, kidney and lung; lower levels were found in the spleen and gut, and the lowest, in the brain. The N-desmethyl derivative of pCOOH-DMT was not detectable in plasma or tissues of mice treated with the drug. Therefore, the previous evidence of low N-demethylation of pCOOH-DMT was confirmed. pCOOH-DMT glucuronide was identified by mass spectrometry and quantified by high-performance liquid chromatography (HPLC) in plasma, tissues and urine samples. pCOOH-DMT glucuronide appears to be the major urinary metabolite of pCOOH-DMT in mice. Another metabolite identified by mass spectrometry and quantified by HPLC in some tissues and urine was pCOOH-DMT glycinate.

Original languageEnglish
Pages (from-to)354-358
Number of pages5
JournalCancer Chemotherapy and Pharmacology
Volume24
Issue number6
DOIs
Publication statusPublished - Nov 1989

ASJC Scopus subject areas

  • Pharmacology
  • Oncology
  • Cancer Research

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