CYCLOPHOSPHAMIDE ANHYDROUS

Details

Stereochemistry	ACHIRAL
Molecular Formula	C7H15Cl2N2O2P
Molecular Weight	261.086
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

ClCCN(CCCl)P1(=O)NCCCO1

InChI

InChIKey=CMSMOCZEIVJLDB-UHFFFAOYSA-N

InChI=1S/C7H15Cl2N2O2P/c8-2-5-11(6-3-9)14(12)10-4-1-7-13-14/h1-7H2,(H,10,12)

HIDE SMILES / InChI

Molecular Formula	C7H15Cl2N2O2P
Molecular Weight	261.086
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 278 Target ID: CHEMBL2311221 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Crosslinking Agent 81

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 8429	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 8429	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 8429	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 8429	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 8429	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 8429	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 8429	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 434 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8429	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 8429	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 8429	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 8429	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 8429	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 8429	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 8429	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 8429	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 80 substrate 1737 inducer 781	activator 22 inducer 389

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
		CYP2B6 547

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C9 1819	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/12739762/	no
CYP2A6 739	activator 214 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15 Page: 15.0	yes
CYP2B6 1001	activator 214 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15 Page: 15.0	yes
CYP2B6 1001	inducer 1573 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3588594/	yes
CYP2C18 13	activator 214 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15 Page: 15.0	yes
CYP2C19 1553	activator 214 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15 Page: 15.0	yes
CYP2C9 1819	activator 214 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15 Page: 15.0	yes
CYP3A4 1925	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/12739762/	yes
CYP3A5 130	activator 214 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15 Page: 15.0	yes
CYP3A4 1925	activator 214 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 1737	substrate 3367 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
Detoxification of urotoxic oxazaphosphorines by sulfhydryl compounds.	1981	6792207
N-acetyl-L-cysteine does not affect the pharmacokinetics or myelosuppressive effect of busulfan during conditioning prior to allogeneic stem cell transplantation.	2003 Aug	12900770
A mouse-based strategy for cyclophosphamide pharmacogenomic discovery.	2003 Oct	12970373
Integrated Population Pharmacokinetic Model of both cyclophosphamide and thiotepa suggesting a mutual drug-drug interaction.	2004 Apr	15379382
Simultaneous quantification of cyclophosphamide, 4-hydroxycyclophosphamide, N,N',N"-triethylenethiophosphoramide (thiotepa) and N,N',N"-triethylenephosphoramide (tepa) in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.	2004 Mar	15039933
ABCC2-mediated biliary transport of 4-glutathionylcyclophosphamide and its contribution to elimination of 4-hydroxycyclophosphamide in rat.	2004 Mar	14617693
Rational combinations of trastuzumab with chemotherapeutic drugs used in the treatment of breast cancer.	2004 May 19	15150302
Diminishing the risk of nonrelapse mortality in hematopoietic stem cell transplantation: Prediction of exposure to the cyclophosphamide metabolite carboxyethylphosphoramide mustard.	2004 Sep	15371987
Population pharmacokinetics of cyclophosphamide and its metabolites 4-hydroxycyclophosphamide, 2-dechloroethylcyclophosphamide, and phosphoramide mustard in a high-dose combination with Thiotepa and Carboplatin.	2005 Dec	16306851
Accuracy, feasibility, and clinical impact of prospective Bayesian pharmacokinetically guided dosing of cyclophosphamide, thiotepa, and carboplatin in high-dose chemotherapy.	2005 Jan 1	15671556
Sparse sampling design for therapeutic drug monitoring of sequentially administered cyclophosphamide, thiotepa, and carboplatin (CTC).	2005 Jun	15905813
Effects of co-medicated drugs on cyclophosphamide bioactivation in human liver microsomes.	2005 Mar	15711186
Significant induction of cyclophosphamide and thiotepa metabolism by phenytoin.	2005 May	15685452
Reduced radiosensitivity and increased CD40 expression in cyclophosphamide-resistant subclones established from human cervical squamous cell carcinoma cells.	2005 Oct	16142355
Aprepitant inhibits cyclophosphamide bioactivation and thiotepa metabolism.	2005 Oct	15838656
Conservation of in vitro drug resistance patterns in epithelial ovarian carcinoma.	2005 Sep	16000215
Real-time dose adjustment of cyclophosphamide in a preparative regimen for hematopoietic cell transplant: a Bayesian pharmacokinetic approach.	2006 Aug 15	16914577
Pharmacogenetics of cyclophosphamide in patients with hematological malignancies.	2006 Jan	16183265
Neutropenia induced in outbred mice by a simplified low-dose cyclophosphamide regimen: characterization and applicability to diverse experimental models of infectious diseases.	2006 Mar 17	16545113
Cyclophosphamide enhances TNF-alpha-induced apoptotic cell death in murine vascular endothelial cell.	2006 Mar 6	16488414
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
New approach to the activation of anti-cancer pro-drugs by metalloporphyrin-based cytochrome P450 mimics in all-aqueous biologically relevant system.	2006 Nov	16965820
Pharmacokinetics of N-2-chloroethylaziridine, a volatile cytotoxic metabolite of cyclophosphamide, in the rat.	2006 Oct	16470409
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
Simultaneous quantification of cyclophosphamide and its active metabolite 4-hydroxycyclophosphamide in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-MS/MS).	2007 Jul 1	17485255
Genetic polymorphisms of CYP2B6 affect the pharmacokinetics/pharmacodynamics of cyclophosphamide in Japanese cancer patients.	2007 Jun	17502835
Mouse mammary tumor virus promoter-containing retroviral promoter conversion vectors for gene-directed enzyme prodrug therapy are functional in vitro and in vivo.	2008	18414588
Epstein-Barr virus renders the infected natural killer cell line, NKL resistant to doxorubicin-induced apoptosis.	2008 Dec 2	18985034
Combined antitumor effect of cyclophosphamide and bromodeoxyuridine in BDF1 mice bearing L1210 ascites tumors.	2008 Jan	18175942
Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance.	2008 Jan 1	18172311
Influence of polymorphisms of drug metabolizing enzymes (CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, GSTA1, GSTP1, ALDH1A1 and ALDH3A1) on the pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide.	2008 Jun	18496131
Targeting Bcl-2 family members with the BH3 mimetic AT-101 markedly enhances the therapeutic effects of chemotherapeutic agents in in vitro and in vivo models of B-cell lymphoma.	2008 Jun 1	18292288
Low-dose metronomic cyclophosphamide treatment mediates ischemia-dependent K-ras mutation in colorectal carcinoma xenografts.	2008 Jun 12	18223682
Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy.	2008 Jun 18	18560594
Pharmacokinetics of cyclophosphamide and thiotepa in a conventional fractionated high-dose regimen compared with a novel simplified unfractionated regimen.	2009 Feb	19155964
Carbamazepine induces bioactivation of cyclophosphamide and thiotepa.	2009 Feb	18437385
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
Does neurokinin-1-receptor antagonist aprepitant diminish the efficacy of cyclophosphamide-based chemotherapy?	2009 Nov	20512296
Cyclophosphamide-metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study.	2010	20459744
Transplacental transfer of anthracyclines, vinblastine, and 4-hydroxy-cyclophosphamide in a baboon model.	2010 Dec	20846713
VEGFR2 heterogeneity and response to anti-angiogenic low dose metronomic cyclophosphamide treatment.	2010 Dec 15	21159176
Fludarabine-based myeloablative regimen as pretransplant conditioning therapy in adult acute leukemia/myelodysplastic syndrome: comparison with oral or intravenous busulfan with cyclophosphamide.	2010 Jun	21120188
Influence of pharmacogenetics on response and toxicity in breast cancer patients treated with doxorubicin and cyclophosphamide.	2010 Mar 16	20179710
In vitro investigation into the potential of a mistletoe extract to alleviate adverse effects of cyclophosphamide.	2010 May-Jun	20486623
Adenoviral delivery of pan-caspase inhibitor p35 enhances bystander killing by P450 gene-directed enzyme prodrug therapy using cyclophosphamide+.	2010 Sep 13	20836875
A day and night difference in the response of the hepatic transcriptome to cyclophosphamide treatment.	2015 Feb	24819615

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 `Fri Dec 15 15:13:25 UTC 2023` Edited by `admin` on `Fri Dec 15 15:13:25 UTC 2023`
Record UNII	6UXW23996M
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CYCLOPHOSPHAMIDE ANHYDROUS

Common Name

English

NSC-26271

Code

English

ANHYDROUS CYCLOPHOSPHAMIDE

Common Name

English

(±)-2-(BIS(2-CHLOROETHYL)AMINO)TETRAHYDRO-2H-1,3,2-OXAZAPHOSPHORINE 2-OXIDE

Systematic Name

English

2H-1,3,2-OXAZAPHOSPHORIN-2-AMINE, N,N-BIS(2-CHLOROETHYL)TETRAHYDRO-, 2-OXIDE

Systematic Name

English

CYCLOPHOSPHAMIDE [HSDB]

Common Name

English

Cyclophosphamide [WHO-DD]

Common Name

English

CYCLOPHOSPHAMIDE LYOPHILIZED

Common Name

English

CYCLOPHOSPHAMIDE ANHYDROUS [MI]

Common Name

English

cyclophosphamide [INN]

Common Name

English

CYCLOPHOSPHAMIDE, ANHYDROUS

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C697