Activation of the anti-cancer drug ifosphamide by rat liver microsomal P450 enzymes
References (39)
- et al.
Studies on the mechanism of denaturation of cytochrome P-450 by cyclophosphamide and its metabolites
J Biol Chem
(1981) Metabolism of oxazaphosphorines
Pharmacol Ther
(1988)- et al.
Feminization of rat hepatic P-450 expression by cisplatin. Evidence for perturbations in the hormonal regulation of steroid-metabolizing enzymes
J Biol Chem
(1988) Rat hepatic P450IIA and P450IIC subfamily expression using catalytic, immunochemical, and molecular probes
Methods Enzymol
(1991)- et al.
Phenobarbital-induced rat liver cytochrome P-450. Purification and characterization of two closely related isozymic forms
J Biol Chem
(1982) - et al.
A simple, non-chromatographic procedure to purify immunoglobulins from serum and ascites fluid
J Immunol Methods
(1987) - et al.
Human liver microsomal steroid metabolism: Identification of the major microsomal steroid hormone 6β-hydroxylase cytochrome P-450 enzyme
Arch Biochem Biophys
(1988) - et al.
Hypoactivity of cytochrome P450 after triacetyloleandomycin adminis-tration
Biochem Pharmacol
(1981) - et al.
Cytochrome P-450 hPCN3, a novel P-450 IIIA gene product that is differentially expressed in adult human liver. cDNA and deduced amino acid sequence and distinct specificities of cDNA-expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and cyclosporine
J Biol Chem
(1989) Interactions of hepatic cytochromes P-450 with steroid hormones. Regioselectivity and stereospecificity of steroid metabolism and hormonal regulation of rat P-450 enzyme expression
Biochem Pharmacol
(1988)
Expression and function of three cytochrome P-450 isozymes in rat extrahepatic tissues
Arch Biochem Biophys
Expression of cytochrome P450b and P450e genes in small intestinal mucosa of rats following treatment with phenobarbital, polyhalogenated biphenyls, and organochlorine pesticides
J Biol Chem
Pharmacology of cyclo-phosphamide and metabolites
Cancer Treat Rep
Identification of the mouse aldehyde dehydrogenases important in aldophosphamide detoxification
Cancer Res
Studies on the metabolism of iso-phosphamide (NSC-109724) in men
Cancer Treat Rep
Phase II trial of ifosphamide with mesna in previously treated metastatic sarcoma
Cancer Treat Rep
Ifosphamide in experimental tumor systems
Semin Oncol
Plasma concentrations of 4-hydroxycyclophosphamide and phosphoramide mustard in patients repeatedly given high doses of cyclophosphamide in preparation for bone marrow transplantation
Cancer Treat Rep
Clinical pharmacokinetics of cyclo-phosphamide
Clin Pharmacokinet
Cited by (73)
Cytotoxic responses of the anticancer drug cyclophosphamide in the mussel Mytilus galloprovincialis and comparative sensitivity with human cells lines
2020, ChemosphereCitation Excerpt :This molecule consists of a prodrug known commercially as Endoxan® or Citoxan®, that requires enzymatic activation to exert its cytotoxic mode of action (Emadi et al., 2009). In humans, CP activation occurs mostly in the liver (Weber and Waxman, 1993) and the resulting metabolites are delivered to neoplastic cells via the bloodstream (Graham et al., 1991). The first step is oxidation of the oxazaphosphorine ring by cytochrome P-450 oxidases to form the unstable intermediate 4-hydroxy-CP (4-OHCP) which coexists with its tautomer, aldophosphamide (Anderson et al., 1995; Hales, 1982).
Chronic ifosfamide toxicity: Kidney pathology and pathophysiology
2014, American Journal of Kidney DiseasesCitation Excerpt :A recent study suggests that tubular cells can transport and concentrate ifosfamide intracellularly by hOCT2 (an organic cation transporter encoded by the SLC22A2 gene).8 Once internalized, the epithelial cytochrome CYP3A4 converts ifosfamide into active nitrogen mustard compounds that alkylate and damage DNA and initiate cell death programs.9-11 Tubular epithelial CYP2B6 can inactivate ifosfamide by N-dechloroethylation to release chloroacetaldehyde, a compound without significant antitumor activity, but potentially responsible for many of ifosfamide's neurotoxic and nephrotoxic side effects.12
Mechanism for the protective effect of diallyl disulfide against cyclophosphamide acute urotoxicity in rats
2014, Food and Chemical ToxicologyCitation Excerpt :It has been demonstrated that CP is a prodrug that requires hepatic biotransformation to exert its urotoxic effect (Fleming, 1997). An alternative, but minor, pathway is the inactivation of CP, and both pathways are dependent on CYP enzymes (Chang et al., 1993; Weber and Waxman, 1993). In male rats, CP is oxidatively activated by CYP2C11 and CYP2B.
Drug interactions between chemotherapeutic regimens and antiepileptics
2008, Clinical Therapeutics