Is metabolized in the liver to phosphoramide mustard?
Normally, ifosfamide is metabolized by endogenous cytochrome P450 in the liver into toxic phosphoramide mustard and acrolein that in turn alkylate DNA and protein respectively.
Does phosphoramide mustard cross the blood brain barrier?
The drug is widely distributed to tissues and has been found to cross the human blood–brain barrier in low concentrations.
What are phosphoramide mustard?
Phosphoramide mustard is an alkylating agent and active metabolite of cyclophosphamide (Item No. 13849). 1. It is formed from cyclophosphamide via the ring-opened tautomer of the cytochrome P450 (CYP) isoform-formed intermediate 4-hydroxycyclophosphamide.
What is phosphoramide?
Phosphoramidites are modified nucleosides and are a standard chemical used in modern DNA synthesis. These molecules permit the sequential addition of new bases to the DNA chain in an exquisitely simple and exceptionally efficient cyclic reaction.
How does cyclophosphamide cause hemorrhagic cystitis?
Cyclophosphamide causes hemorrhagic cystitis by renal excretion of its hepatic metabolite, acrolein, which is urotoxic.
What is the toxicity unique to cyclophosphamide?
Clinically, damage to the bladder (haemorrhagic cystitis), immunosuppression (when not desired) and alopecia are the most significant toxicities associated with cyclophosphamide. Cardiotoxicity is also a possibility when very high doses are given.
Which drug is not an alkylating agent?
Note: Although the platinum-containing anticancer agents, carboplatin, cisplatin, and oxaliplatin are frequently classified as alkylating agents, they are not.
Which drug is an alkylating agent?
Cyclophosphamide — the most widely used alkylating agent of modern times. Chlormethine also known as mechlorethamine or mustine (HN2) — the first alkylating agent to receive regulatory approval.
How do you treat hemorrhagic cystitis?
The best treatment of hemorrhagic cystitis is prevention, especially with cyclophosphamide-induced hemorrhagic cystitis. Adequate hydration to induce brisk diuresis, continuous bladder irrigation, and prophylactic dosing of mesna are important preventive measures.
Where does phosphoramide mustard occur in the body?
Phosphoramide mustard is formed only in cells that have low levels of ALDH. ALDHs are abundant in rapidly proliferating tissues (bone marrow stem cells, liver, and intestinal epithelium) and are protective against the toxic effects of phosphoramide mustard and acrolein by driving the conversion of aldophosphamide to carboxyphosphamide.
How is cyclophosphamide mustard metabolized in the liver?
Cyclophosphamide is a prodrug and is metabolized to active alkylating agents, principally by microsomal enzymes in the liver. Phosphoramide mustard and acrolein, endpoints of the metabolic pathway, are believed to be primarily responsible for the antitumor activity and bladder toxicity respectively.
Which is an oxazaphosphorine nitrogen mustard alkylating agent?
Cyclophosphamide is an oxazaphosphorine nitrogen mustard alkylating agent used in combination with other chemotherapeutic agents in the treatment of a variety of malignancies. Prior to activation, the cyclic phosphamide group is cleaved to phosphoramide mustard and acrolein (Sladek 1988 ).