4-HYDROXYCYCLOPHOSPHAMIDE

Details

Stereochemistry	MIXED
Molecular Formula	C7H15Cl2N2O3P
Molecular Weight	277.085
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1CCOP(=O)(N1)N(CCCl)CCCl

InChI

InChIKey=RANONBLIHMVXAJ-UHFFFAOYSA-N

InChI=1S/C7H15Cl2N2O3P/c8-2-4-11(5-3-9)15(13)10-7(12)1-6-14-15/h7,12H,1-6H2,(H,10,13)

HIDE SMILES / InChI

Molecular Formula	C7H15Cl2N2O3P
Molecular Weight	277.085
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: http://www.myelomabeacon.com/resources/2008/10/15/cyclophosphamide/

Cyclophosphamide (the generic name for Cytoxan, Neosar, Revimmune), also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group. It is used to treat various types of cancer and some autoimmune disorders. It is a "prodrug"; it is converted in the liver to active forms that have chemotherapeutic activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 247 Target ID: CHEMBL2311221 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Crosslinking Agent 80

Conditions

Condition	Modality	Highest Phase	Product
Hodgkin’s disease, lymphocytic lymphoma (nodular or diffuse) 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8360	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date -3.06806391E11
Multiple myeloma 159 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8360	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date -3.06806391E11
Chronic lymphocytic leukemia 59 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8360	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date -3.06806391E11
Mycosis fungoides 30 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8360	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date -3.06806391E11
Neuroblastoma 25 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8360	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date -3.06806391E11
Adenocarcinoma of the ovary 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8360	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date -3.06806391E11
Retinoblastoma 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8360	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date -3.06806391E11
Breast cancer 431 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8360	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date -3.06806391E11
Minimal change nephrotic syndrome 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8360	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date -3.06806391E11
Hodgkin’s disease mixed-cell type lymphoma 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8360	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date -3.06806391E11
Hodgkin’s disease histiocytic lymphoma 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8360	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date -3.06806391E11
Burkitt’s lymphoma 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8360	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date -3.06806391E11
Chronic granulocytic leukemia 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8360	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date -3.06806391E11
Acute myelogenous and monocytic leukemia 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8360	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date -3.06806391E11
Acute lymphoblastic leukemia 27 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8360	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date -3.06806391E11

C_max

Value	Dose	Co-administered	Analyte	Population
1234 μg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24022191	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered: Imatinib \| Bevacizumab	Imatinib \| Bevacizumab	CYCLOPHOSPHAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
17587 μg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24022191	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered: Imatinib \| Bevacizumab	Imatinib \| Bevacizumab	CYCLOPHOSPHAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
10.8 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24022191	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered: Imatinib \| Bevacizumab	Imatinib \| Bevacizumab	CYCLOPHOSPHAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
80% DRUG LABEL https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/0e1cb955-99c8-4fe5-89d1-399c8e52174e/spl-doc?hl=cyclophosphamide			CYCLOPHOSPHAMIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
200 mg/m2 2 times / day multiple, intravenous MTD Dose: 200 mg/m2, 2 times / day Route: intravenous Route: multiple Dose: 200 mg/m2, 2 times / day Co-administed with:: Clofarabine, i.v(40 mg/m(2) daily × 3 days) Sources: https://pubmed.ncbi.nlm.nih.gov/24440659 Page: p.5, 16	unhealthy, 21-72 n = 5 Health Status: unhealthy Condition: Acute lymphoblastic leukemia Age Group: 21-72 Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/24440659 Page: p.5, 16	Other AEs: Bilirubin total increased, Diarrhea... Other AEs: Bilirubin total increased (grade 3, 20%) Diarrhea (grade 3, 20%) Sources: https://pubmed.ncbi.nlm.nih.gov/24440659 Page: p.5, 16
300 mg/m2 2 times / day multiple, intravenous Studied dose Dose: 300 mg/m2, 2 times / day Route: intravenous Route: multiple Dose: 300 mg/m2, 2 times / day Co-administed with:: Clofarabine, i.v(40 mg/m(2) daily × 3 days) Sources: https://pubmed.ncbi.nlm.nih.gov/24440659 Page: p.5, 16	unhealthy, 21-72 n = 25 Health Status: unhealthy Condition: Acute lymphoblastic leukemia Age Group: 21-72 Sex: M+F Population Size: 25 Sources: https://pubmed.ncbi.nlm.nih.gov/24440659 Page: p.5, 16	DLT: Diarrhea, Lipase increased... Dose limiting toxicities: Diarrhea (grade 3-5, 12%) Lipase increased (grade 4, 4%) Transaminases increased (grade 3-5, 12%) Nausea and vomiting (grade 3-5, 4%) Sources: https://pubmed.ncbi.nlm.nih.gov/24440659 Page: p.5, 16
3300 mg/m2 single, intravenous Highest studied dose Dose: 3300 mg/m2 Route: intravenous Route: single Dose: 3300 mg/m2 Co-administed with:: paclitaxel, i.v(160 mg/m2) Sources: https://pubmed.ncbi.nlm.nih.gov/8558227 Page: p.98	unhealthy, 26-64 n = 6 Health Status: unhealthy Condition: Breast cancer Age Group: 26-64 Sex: F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/8558227 Page: p.98	DLT: Neutropenia, Thrombocytopenia... Dose limiting toxicities: Neutropenia (grade 4, 33.3%) Thrombocytopenia (16.7%) Neutropenia (16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/8558227 Page: p.98
2700 mg/m2 single, intravenous MTD Dose: 2700 mg/m2 Route: intravenous Route: single Dose: 2700 mg/m2 Co-administed with:: paclitaxel, i.v(160 mg/m2) Sources: https://pubmed.ncbi.nlm.nih.gov/8558227 Page: p.98	unhealthy, 26-64 n = 6 Health Status: unhealthy Condition: Breast cancer Age Group: 26-64 Sex: F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/8558227 Page: p.98	DLT: Neutropenia, Thrombocytopenia... Dose limiting toxicities: Neutropenia (grade 4, 16.7%) Thrombocytopenia (16.7%) Neutropenia (16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/8558227 Page: p.98
2000 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 2000 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 2000 mg/m2, 1 times / 3 weeks Co-administed with:: paclitaxel, i.v(200 mg/m2, once in 3 weeks, 5 cycles) Sources: https://pubmed.ncbi.nlm.nih.gov/9296218 Page: p.658	unhealthy, 27 - 70 n = 6 Health Status: unhealthy Condition: Breast cancer Age Group: 27 - 70 Sex: F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/9296218 Page: p.658	DLT: Febrile neutropenia, Thrombocytopenia... Dose limiting toxicities: Febrile neutropenia (33.3%) Thrombocytopenia (grade 4, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/9296218 Page: p.658
100 mg 1 times / day multiple, oral Highest studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Co-administed with:: paclitaxel, i.v(175 mg/m(2) (Day 1), 6 cycles) Sources: https://pubmed.ncbi.nlm.nih.gov/19117344 Page: p.519	unhealthy, 47-78 n = 6 Health Status: unhealthy Condition: Urothelial bladder cancer Age Group: 47-78 Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/19117344 Page: p.519	DLT: Neutropenia, Thrombocytopenia... Dose limiting toxicities: Neutropenia (grade 4, 33.3%) Thrombocytopenia (grade 4, 16.7%) Constipation (grade 3, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/19117344 Page: p.519
50 mg 1 times / day multiple, oral MTD Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Co-administed with:: paclitaxel, i.v(175 mg/m(2) (Day 1), 12 cycles) Sources: https://pubmed.ncbi.nlm.nih.gov/19117344 Page: p.519	unhealthy, 47-78 n = 6 Health Status: unhealthy Condition: Urothelial bladder cancer Age Group: 47-78 Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/19117344 Page: p.519	Sources: https://pubmed.ncbi.nlm.nih.gov/19117344 Page: p.519
5 mg/kg 1 times / day multiple, oral (max) Recommended Dose: 5 mg/kg, 1 times / day Route: oral Route: multiple Dose: 5 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Hodgkin’s disease\| lymphocytic lymphoma\| mixed-cell type lymphoma\| histiocytic lymphoma\| Burkitt’s lymphoma\| multiple myeloma\| leukemias\|mycosis fungoides\| neuroblastoma\| adenocarcinoma of ovary\| retinoblastoma\| breast carcinoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf Page: p.1	Disc. AE: Myelosuppression, Immunosuppression... AEs leading to discontinuation/dose reduction: Myelosuppression Immunosuppression Bone marrow failure Infection Urinary tract toxicity Toxicity renal Cystitis hemorrhagic Pyelitis Ureteritis Hematuria Cardiotoxicity Myocarditis Myopericarditis Pericardial effusion Arrhythmia (NOS) Congestive heart failure Pulmonary toxicity Pneumonitis Pulmonary fibrosis Pulmonary veno-occlusive disease Respiratory failure Metastases Venoocclusive liver disease Fetal damage Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf Page: p.1
50 mg/kg multiple, intravenous (total\|max) Recommended Dose: 50 mg/kg Route: intravenous Route: multiple Dose: 50 mg/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Hodgkin’s disease\| lymphocytic lymphoma\| mixed-cell type lymphoma\| histiocytic lymphoma\| Burkitt’s lymphoma\| multiple myeloma\| leukemias\|mycosis fungoides\| neuroblastoma\| adenocarcinoma of ovary\| retinoblastoma\| breast carcinoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf Page: p.1	Disc. AE: Myelosuppression, Immunosuppression... AEs leading to discontinuation/dose reduction: Myelosuppression Immunosuppression Bone marrow failure Infection Urinary tract toxicity Toxicity renal Cystitis hemorrhagic Pyelitis Ureteritis Hematuria Cardiotoxicity Myocarditis Myopericarditis Pericardial effusion Arrhythmia (NOS) Congestive heart failure Pulmonary toxicity Pneumonitis Pulmonary fibrosis Pulmonary veno-occlusive disease Respiratory failure Metastases Venoocclusive liver disease Fetal damage Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf Page: p.1

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
activator 77 substrate 1709 inducer 768	activator 21 inducer 383

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
		CYP2B6 538

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C9 1803	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/12739762/	no
CYP2A6 736	activator 210 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15 Page: 15.0	yes
CYP2B6 985	activator 210 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15 Page: 15.0	yes
CYP2B6 985	inducer 1542 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3588594/	yes
CYP2C18 13	activator 210 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15 Page: 15.0	yes
CYP2C19 1537	activator 210 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15 Page: 15.0	yes
CYP2C9 1803	activator 210 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15 Page: 15.0	yes
CYP3A4 1909	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/12739762/	yes
CYP3A5 130	activator 210 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15 Page: 15.0	yes
CYP3A4 1909	activator 210 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814316/ Page: 15.0	yes	weak (co-administration study) Comment: coadministration with ketoconazole: had small effect on CYCLOPHOSPHAMIDE plasma concentration Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814316/ Page: 15.0

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1709	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814316/	yes	DECP 3	yes (co-administration study) Comment: coadministration with ketoconazole: caused a KTZ dose-dependent decrease in main parameters of DECP (Cmax, Tmax, and AUC0–∞) and provided magnitude exposure of DECP (more than a 50% AUC decrease) as a consequence of CYP3A inhibition Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814316/

PubMed

Title	Date	PubMed
Cyclophosphamide-induced hemorrhagic cystitis in children with leukemia.	1975 Nov	1059500
Detoxification of urotoxic oxazaphosphorines by sulfhydryl compounds.	1981	6792207
Thiotepa-associated cardiomyopathy during blood or marrow transplantation: association with the female sex and cardiac risk factors.	1999	10534063
[Crescentic glomerulonephritis with anti neutrophil cytoplasmic antibody in children. Cases report].	1999 Aug	10752259
Antiemetic efficacy of granisetron plus dexamethasone in bone marrow transplant patients receiving chemotherapy and total body irradiation.	1999 Feb	10084258
[Veno-occlusive disease of the liver and POEMS syndrome].	1999 Feb 20	10083875
The uroprotection of mesna on cyclophosphamide cystitis in rats. Its consequences on behaviour and brain activities.	1999 Jun	10457601
Prevention of cyclophosphamide-induced hemorrhagic cystitis by glucose-mannose binding plant lectins.	1999 Jun	10332487
Evaluation of uroprotective efficacy of amifostine against cyclophosphamide induced hemorrhagic cystitis.	1999 Mar	10100560
Delayed methotrexate clearance in a patient with sickle cell anemia and osteosarcoma.	1999 Mar-Apr	10206466
Alterations in spinal cord Fos protein expression induced by bladder stimulation following cystitis.	2000 Apr	10749792
Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer.	2000 Apr 1	10766175
Adjuvant doxorubicin and cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy in premenopausal women with axillary lymph node positive breast carcinoma.	2000 Dec 15	11135211
Urinary bladder involvement in patients with systemic lupus erythematosus: with review of the literature.	2000 Jan	10714091
Long-term remission in an elderly patient with mantle cell leukemia treated with low-dose cyclophosphamide.	2000 Jan	10602166
Nitric oxide-producing CD11b(+)Ly-6G(Gr-1)(+)CD31(ER-MP12)(+) cells in the spleen of cyclophosphamide-treated mice: implications for T-cell responses in immunosuppressed mice.	2000 Jan 1	10607705
[Cyclophosphamide-induced renal pelvic tumor--a case report].	2000 Mar	10806575
Quantitative prediction of catalepsy induced by amoxapine, cinnarizine and cyclophosphamide in mice.	2000 May	11180191
Dramatic aneurysm regression in polyarteritis nodosa following high dose pulse cyclophosphamide.	2000 May	10813312
Up-regulation of pituitary adenylate cyclase-activating polypeptide in urinary bladder pathways after chronic cystitis.	2000 May 8	10754506
Report of severe neurotoxicity with cyclophosphamide.	2000 Nov-Dec	11132226
Cytochrome P-450 2C9 sensitizes human prostate tumor cells to cyclophosphamide via a bystander effect.	2000 Oct	10991840
Mixed chimerism, heart, and skin allograft tolerance in cyclophosphamide-induced tolerance.	2000 Sep 27	11014644
Hypersensitivity reactions to carboplatin administration are common but not always severe: a 10-year experience.	2001	11528251
Doxorubicin and taxane combination regimens for metastatic breast cancer: focus on cardiac effects.	2001 Aug	11552226
Serum cardiac troponin I levels and ECG/Echo monitoring in breast cancer patients undergoing high-dose (7 g/m(2)) cyclophosphamide.	2001 Aug	11535996
Cyclophosphamide-induced hemorrhagic cystitis in rats that underwent colocystoplasty: experimental study.	2001 Feb	11176454
Intraneoplastic polymer-based delivery of cyclophosphamide for intratumoral bioconversion by a replicating oncolytic viral vector.	2001 Feb 1	11221871
Erythropoietin restores the anemia-induced reduction in cyclophosphamide cytotoxicity in rat tumors.	2001 Feb 15	11245434
Involvement of hypogastric and pelvic nerves for conveying cystitis induced nociception in conscious rats.	2001 Jul	11435893
Bladder carcinoma associated with cyclophosphamide therapy for ovarian cancer occurring with a latency of 20 years.	2001 Jul	11426986
What is proper treatment for Wegener granulomatosis?	2001 Jul 23	11485512
Transitional cell carcinoma of the urinary bladder following exposure to cyclophosphamide in childhood.	2001 Jun	11475121
Frequent, moderate-dose cyclophosphamide administration improves the efficacy of cytochrome P-450/cytochrome P-450 reductase-based cancer gene therapy.	2001 Jun 1	11389073
High-dose paclitaxel in combination with doxorubicin, cyclophosphamide and peripheral blood progenitor cell rescue in patients with high-risk primary and responding metastatic breast carcinoma: toxicity profile, relationship to paclitaxel pharmacokinetics and short-term outcome.	2001 Jun 15	11401310
Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2.	2001 Mar 15	11248153
Contribution of alveolar phagocytes to antibiotic efficacy in an experimental lung infection with Streptococcus pneumoniae.	2001 May	11545565
Dominant role of intercellular adhesion molecule-1 in the pathogenesis of autoimmune diabetes in non-obese diabetic mice.	2001 Sep	11591119
Prevention of further cyclophosphamide induced hemorrhagic cystitis by hyperbaric oxygen and mesna in guinea pigs.	2001 Sep	11490309
Real-time dose adjustment of cyclophosphamide in a preparative regimen for hematopoietic cell transplant: a Bayesian pharmacokinetic approach.	2006 Aug 15	16914577
Rapid quantitation of cyclophosphamide metabolites in plasma by liquid chromatography-mass spectrometry.	2006 May 1	16581318
High exposures to bioactivated cyclophosphamide are related to the occurrence of veno-occlusive disease of the liver following high-dose chemotherapy.	2006 May 8	16622453
A mouse model with liver-specific deletion and global suppression of the NADPH-cytochrome P450 reductase gene: characterization and utility for in vivo studies of cyclophosphamide disposition.	2007 Apr	17218484
Fluconazole coadministration concurrent with cyclophosphamide conditioning may reduce regimen-related toxicity postmyeloablative hematopoietic cell transplantation.	2007 Jul	17580253
Epstein-Barr virus renders the infected natural killer cell line, NKL resistant to doxorubicin-induced apoptosis.	2008 Dec 2	18985034
Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy.	2008 Jun 18	18560594
Population pharmacokinetics of cyclophosphamide and metabolites in children with neuroblastoma: a report from the Children's Oncology Group.	2009 Jan	18927240
Altered cyclophosphamide and thiotepa pharmacokinetics in a patient with moderate renal insufficiency.	2009 Jan	18431571
Dominant effect of antiangiogenesis in combination therapy involving cyclophosphamide and axitinib.	2009 Jan 15	19147763
Cyclophosphamide-metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study.	2010	20459744

Patents

Sample Use Guides

In Vivo Use Guide

40-50 mg per kg in divided doses over 2 to 5 days in malignant diseases and 2 mg per kg daily for 8 to 12 weeks in minimal change nephrotic sindrome

Route of Administration: Intravenous

In Vitro Use Guide

from 20 to 160 ug/ml

Substance Class	Chemical Created by `admin` on `Thu Jul 06 14:48:43 UTC 2023` Edited by `admin` on `Thu Jul 06 14:48:43 UTC 2023`
Record UNII	1XBF4E50HS
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

4-HYDROXYCYCLOPHOSPHAMIDE

Common Name

English

NSC-196562

Code

English

2-(BIS(2-CHLOROETHYL)AMINO)TETRAHYDRO-2H-1,3,2-OXAZAPHOSPHORIN-4-OL 2-OXIDE

Systematic Name

English

Code System Code Type Description

EPA CompTox

DTXSID90960669