Identification of prodrug, active drug, and metabolites in an ADEPT clinical study

Cell Biophys. Jan-Jun 1993;22(1-3):9-26. doi: 10.1007/BF03033864.

Abstract

Antibody-directed enzyme prodrug therapy (ADEPT) involves two phases. The first is an antibody-enzyme conjugate that localizes to tumor. The second phase is a prodrug that is administered when the enzyme-conjugate has cleared from blood and other nontumor tissues. In the pilot-scale clinical trial, the prodrug has been measured--in the plasma of patients, by liquid chromatography (HPLC) and by liquid chromatography-mass spectrometry (LC-MS). Active drug has been detected and metabolites identified. An indirect measurement of enzyme-conjugate in the plasma of patients has also been developed.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / therapeutic use
  • Benzoates* / blood
  • Benzoates* / metabolism*
  • Benzoates* / pharmacology*
  • Chromatography, High Pressure Liquid
  • Glutamates / blood
  • Glutamates / metabolism*
  • Glutamates / pharmacology*
  • Humans
  • Immunotoxins / blood
  • Immunotoxins / therapeutic use*
  • Mass Spectrometry
  • Mice
  • Nitrogen Mustard Compounds / blood
  • Nitrogen Mustard Compounds / metabolism*
  • Nitrogen Mustard Compounds / pharmacology*
  • Prodrugs / metabolism*
  • Prodrugs / therapeutic use
  • gamma-Glutamyl Hydrolase / blood
  • gamma-Glutamyl Hydrolase / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Benzoates
  • Glutamates
  • Immunotoxins
  • Nitrogen Mustard Compounds
  • Prodrugs
  • 4-((2-chloroethyl) (2-mesyloxyethyl)amino)benzoic acid
  • 4-((2-chloroethyl)(2-mesyloxyethyl)amino)benzoylglutamic acid
  • gamma-Glutamyl Hydrolase