Identification of prodrug, active drug, and metabolites in an ADEPT clinical study.
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.
Springer
C J
CJ
Department of Medical Oncology, Charing Cross Hospital, London, England.
Poon
G K
GK
Sharma
S K
SK
Bagshawe
K D
KD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000627:therapeutic use; D001565:Benzoates / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D005971:Glutamates / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D000922:Immunotoxins / Q000097:blood / Q000627:therapeutic use*; D013058:Mass Spectrometry; D051379:Mice; D009588:Nitrogen Mustard Compounds / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D011355:Prodrugs / Q000378:metabolism* / Q000627:therapeutic use; D011623:gamma-Glutamyl Hydrolase / Q000097:blood / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D001565:Benzoates; D005971:Glutamates; D000922:Immunotoxins; D009588:Nitrogen Mustard Compounds; D011355:Prodrugs; C092575:4-((2-chloroethyl) (2-mesyloxyethyl)amino)benzoic acid; C092574:4-((2-chloroethyl)(2-mesyloxyethyl)amino)benzoylglutamic acid; D011623:gamma-Glutamyl Hydrolase