Anticancer drugs ifosfamide

Electrochemical oxidation of anticancer drugs ifosfamide and cyclophosphamide produced in high yield methoxylated analogues of the key hydroxy-metabolites of these oxazaphosphorine prodrugs (Scheme 19). ... 

Blaschke et al. reported on metabolic studies of the anticancer drug ifosfamide [7] using Chirasil-val as a chiral stationary phase (49). In urine extracts of cancer patients, the K-enantiomer was found to be enriched. 

Solutes containing asymmetric sulfur atomes or asymmetric phosphorous atoms can be resolved v/ith or without an aromatic moiety in the molecule. For example, the anticancer drug ifosfamide, an oxazaphos-phorane not containing an aromatic moiety, has been resolved on this type of CSP (73). In addition, these are excellent CSPs for the resolution of enantiomeric molecules with an axis of dissymmetry (atrop isomers) (9-11). 

In animal studies, NAC has been shown to prevent hemorrhagic cystitis that results from administration of cyclophosphamide or its position isomer ifosfamide. Hemorrhagic cystitis results from the toxic effect of acrolein, a metabolic product of cyclophosphamide or its position isomer ifosfamide. The mechanism whereby NAC prevents this toxicity may be prevention of the intracellular depletion of antioxidants, such as GSH, by acrolein. Concomitant administration of NAC with cyclophosphamide or ifosfamide does not impair antineoplastic activity, because both anticancer drugs are inactive until they are metabolized by the liver to their phosphoramide mustard metabolites. 

Mesna is used to prevent or ameliorate hemorrhagic cystitis produced by the anticancer drugs cyclophosphamide and ifosfamide. It is excreted by the kidney and binds and detoxifies acrolein in the urine mesna also prevents the breakdown of acrolein precursors. It is also used as a mucolytic. 

Hartmann JT, Knop S, Fels LM, van Vangerow A, Stolte H, Kanz L, Bokemeyer C. The use of reduced doses of amifostine to ameliorate nephrotoxicity of cisplatin/ifosfamide-based chemotherapy in patients with solid tumors. Anticancer Drugs 2000 ll(l) l-6. 

The anticancer drugs cisplatin cyclophosphamide - and ifosfamide alter the profile of P450 enzyme expression in liver and perhaps other tissues, at least in part due to the hormonal perturbations that these cytotoxic agents induce. Treatment of adult male rats with a single dose of cisplatin depletes serum androgen, and this effect persists for up to 28 days after drug administration . Serum androgen depletion by cisplatin is associated with a feminization of hepatic liver enzyme expression. Thus, cisplatin-treated male rats have elevated levels of the female-predominant... 

This potent anticancer drug is now widely used in chemotherapy in association with several other drugs (e.g., vinblastine, methotrexate, carboplatine, ifosfamide, or etoposide) in the treatment of Hodgkin s disease (9), of head and neck cancers (JO, 11), of disseminated germ cell tumors (12), and of poor-prognosis epidemic Kaposi s sarcoma (13) (for previous articles on the clinical use of BLM, see references listed in Refs. 9-13). 

Chemoprotective agents are the drugs that can help mitigate the toxic effects of anticancer drugs. For example, the nitrogen mustard ifosfamide causes nephrotoxicity (hemorrhagic cystitis and hematuria), which was attributed to... 

Crommentuyn KML, Schellens JHM, Van Den Berg JD, Beijnen JH (1998) In-vitro Metabolism of Anticancer Drugs, Methods and Applications Paclitaxel, Docetaxel, Tamoxifen and Ifosfamide. Cancer Treat Rev 24 345... 

IFOSFAMIDE 1. ANTIBIOTICS-rifampicin 2. ANTICANCER AND IMMUNOMODULATING DRUGS - dexamethasone 3. ANTIDEPRESSANTS-St John s wort 4. ANTI EPILEPTICS -carbamazepine, phenytoin, phenobarbital t rate of biotransformation to 4-hydroxyifbsfamide, the active metabolite, but there is no change in AUC of 4-hydroxyifosfamide Due to t rate of metabolism and of clearance owing to induction of CYP3A4 and CYP2D6 Be aware - clinical significance may be minimal or none... 

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