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Identification of prodrug, active drug, and metabolites in an ADEPT clinical study
C J Springer1, G K Poon, S K Sharma
1Department of Medical Oncology, Charing Cross Hospital, London, England.
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.