Table 1

Effect of enzyme activity on cyclophosphamide (CPA) pharmacology

When the 4-position of the oxazaphosphorine ring is oxidized more rapidly, there is increased production of phosphamide mustard (PAM) and greater antitumor effect. With increased oxidation of the mustard sidechains or increased oxidation of aldophosphamide, PAM production is decreased, producing less antitumor effect. Up arrows indicate an increase in activity or concentration, down arrows indicate the reverse, and dash indicates no net change.

Metabolic changeMetabolite
CPAPAMDCE CPAaCarboxy PA
↑ Ring oxidation
↑ Sidechain oxidation
↑ Aldehyde dehydrogenase
  • a DCE CPA, dechlorethyl cyclophosphamide; Carboxy PA, carboxyphosphamide.