Cyclophosphamide is an alkylating agent that requires hepatic bioactivation. The active metabolite responsible for its cytotoxic and immunosuppressive effect is:
- A Acrolein
- B 4-Hydroxycyclophosphamide
- C Phosphoramide mustard ✓
- D Aldophosphamide
Explanation
Cyclophosphamide is hydroxylated by hepatic CYP2B6 (and CYP3A4) to 4-hydroxycyclophosphamide, which spontaneously equilibrates with its ring-open form aldophosphamide. Aldophosphamide undergoes beta-elimination to yield two products: phosphoramide mustard (the active alkylating species that cross-links DNA guanine residues) and acrolein (the toxic byproduct responsible for haemorrhagic cystitis via urothelial damage). Mesna is given to neutralise acrolein. The intermediate metabolites 4-hydroxycyclophosphamide and aldophosphamide are transport forms, not the ultimate alkylating species.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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