All of the following are true about Ifosfamide except:
(A) It is nitrogen mustard (B) Metabolised by CYP3A4 to form active metabolite (C) Chloracetaldehyde is active form (D) Less neurotoxic than cyclophosphamide
(D) Ans. d. Less neurotoxic than cyclophosphamideAt equivalent doses, the rate of chloroacetaldehyde generation with ifosfamide is 40 times greater than with cyclophosphamide. At equivalent doses, the rate of chloroacetaldehyde generation with ifosfamide is 40 times greater than with cyclophosphamide therefore it produces more platelet suppression, neurotoxicity and urothelial damage.IfosfamideIfosfamide is a synthetic analogue of cyclophosphamideIt is a nitrogen mustard alkylating agentMetabolism:Ifosfamide is a prodrug that requires metabolic activation by microsomal liver enzymes to produce biologically active compounds.Activation is mediated by cytochrome p450 --> CYP3A4 and deactivated by CYP3A-4 and CYP2B6The metabolic activation of Ifosfamide is an autoinducible process and besides producing active cytotoxic metabolites it also results in generation of some toxic metabolic byproducts that are responsible Side-Effects/Toxicity:Ifosfamide is a cyclophosphamide analogue, it has all the potential adverse effects Ifosfamide metabolite, rather than the parent drug is responsible for toxicity.Well known toxic metabolites of Ifosfamide: Acrolein and chloroacetaldehyde.Acrolein is responsible for Ifosfamide induced hemorrhagic cystitis.Chloroacetaldehyde is responsible for renal tubular damage and neurotoxicity.At equivalent doses, the rate of chloroacetaldehyde generation with ifosfamide is 40 timescyclophosphamide therefore it produces more platelet suppression, neurotoxicity and urothelial