Details
Stereochemistry | UNKNOWN |
Molecular Formula | C7H15Cl2N2O3P |
Molecular Weight | 277.085 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC1CCOP(=O)(NCCCl)N1CCCl
InChI
InChIKey=JHUJMHKRHQPBRG-UHFFFAOYSA-N
InChI=1S/C7H15Cl2N2O3P/c8-2-4-10-15(13)11(5-3-9)7(12)1-6-14-15/h7,12H,1-6H2,(H,10,13)
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 | ( + / - ) |
DescriptionSources: http://www.ncbi.nlm.nih.gov/pubmed/?term=17464949
Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=17464949
Ifosfamide (IF) is a widely used antitumor prodrug. It is in the oxazaphosphorine class of alkylating agents, and it is effective against solid tumors. Ifosfamide mechanism of crosslinking DNA plays a major role in preventing cancer cells from proliferating. Ifosfamide is approved by FDA for the treatment of germ cell testicular cancer.
CNS Activity
Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3253870/
Curator's Comment: Ifosfamide crosses the blood-brain barrier and may cause encephalopathy.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2311221 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | IFEX Approved UseIfosfamide injection, used in combination with certain other approved antineoplastic agents, is indicated for third line chemotherapy of germ cell testicular cancer. It should be used in combination with a prophylactic agent for hemorrhagic cystitis, such as mesna. Launch Date5.9944318E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
200 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1795004 |
1.5 g/m² single, oral dose: 1.5 g/m² route of administration: Oral experiment type: SINGLE co-administered: |
IFOSFAMIDE blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
203 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1795004 |
1.5 g/m² single, intravenous dose: 1.5 g/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
IFOSFAMIDE blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1360 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1795004 |
1.5 g/m² single, oral dose: 1.5 g/m² route of administration: Oral experiment type: SINGLE co-administered: |
IFOSFAMIDE blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
1520 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1795004 |
1.5 g/m² single, intravenous dose: 1.5 g/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
IFOSFAMIDE blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
7.54 mM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8339288 |
3 g/m² 1 times / day multiple, intravenous dose: 3 g/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IFOSFAMIDE blood | Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1795004 |
1.5 g/m² single, oral dose: 1.5 g/m² route of administration: Oral experiment type: SINGLE co-administered: |
IFOSFAMIDE blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
5.6 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1795004 |
1.5 g/m² single, intravenous dose: 1.5 g/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
IFOSFAMIDE blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
2.12 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8339288 |
3 g/m² 1 times / day multiple, intravenous dose: 3 g/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
IFOSFAMIDE blood | Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
100% |
IFOSFAMIDE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
18 g/m2 1 times / day multiple, intravenous (total) MTD Dose: 18 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 18 g/m2, 1 times / day Sources: Page: p.1090 |
unhealthy, 45 n = 6 Health Status: unhealthy Condition: Sarcoma Age Group: 45 Sex: M+F Population Size: 6 Sources: Page: p.1090 |
DLT: Neutropenia, Infection... Dose limiting toxicities: Neutropenia (grade 4, 83.3%) Sources: Page: p.1090Infection (severe, 33.3%) Thrombocytopenia (grade 4, 66.7%) |
2.25 g/m2 1 times / day multiple, intravenous MTD Dose: 2.25 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 2.25 g/m2, 1 times / day Co-administed with:: doxorubicin, i.v(45 mg/m2) Sources: Page: p.6 |
unhealthy, 45 n = 3 Health Status: unhealthy Condition: Breast cancer Age Group: 45 Sex: F Population Size: 3 Sources: Page: p.6 |
DLT: Neutropenia, Febrile neutropenia... Dose limiting toxicities: Neutropenia (grade 4, 66.7%) Sources: Page: p.6Febrile neutropenia (grade 5, 33.3%) Thrombocytopenia (grade 4, 66.7%) Anemia (grade 4, 66.7%) |
1.2 g/m2 1 times / day multiple, intravenous Recommended Dose: 1.2 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 1.2 g/m2, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Testicular cancer Sources: Page: p.1 |
Disc. AE: Nephrotoxicity, Renal failure... AEs leading to discontinuation/dose reduction: Nephrotoxicity (severe) Sources: Page: p.1Renal failure (severe) Cystitis hemorrhagic (severe) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Thrombocytopenia | grade 4, 66.7% DLT |
18 g/m2 1 times / day multiple, intravenous (total) MTD Dose: 18 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 18 g/m2, 1 times / day Sources: Page: p.1090 |
unhealthy, 45 n = 6 Health Status: unhealthy Condition: Sarcoma Age Group: 45 Sex: M+F Population Size: 6 Sources: Page: p.1090 |
Neutropenia | grade 4, 83.3% DLT |
18 g/m2 1 times / day multiple, intravenous (total) MTD Dose: 18 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 18 g/m2, 1 times / day Sources: Page: p.1090 |
unhealthy, 45 n = 6 Health Status: unhealthy Condition: Sarcoma Age Group: 45 Sex: M+F Population Size: 6 Sources: Page: p.1090 |
Infection | severe, 33.3% DLT |
18 g/m2 1 times / day multiple, intravenous (total) MTD Dose: 18 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 18 g/m2, 1 times / day Sources: Page: p.1090 |
unhealthy, 45 n = 6 Health Status: unhealthy Condition: Sarcoma Age Group: 45 Sex: M+F Population Size: 6 Sources: Page: p.1090 |
Anemia | grade 4, 66.7% DLT |
2.25 g/m2 1 times / day multiple, intravenous MTD Dose: 2.25 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 2.25 g/m2, 1 times / day Co-administed with:: doxorubicin, i.v(45 mg/m2) Sources: Page: p.6 |
unhealthy, 45 n = 3 Health Status: unhealthy Condition: Breast cancer Age Group: 45 Sex: F Population Size: 3 Sources: Page: p.6 |
Neutropenia | grade 4, 66.7% DLT |
2.25 g/m2 1 times / day multiple, intravenous MTD Dose: 2.25 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 2.25 g/m2, 1 times / day Co-administed with:: doxorubicin, i.v(45 mg/m2) Sources: Page: p.6 |
unhealthy, 45 n = 3 Health Status: unhealthy Condition: Breast cancer Age Group: 45 Sex: F Population Size: 3 Sources: Page: p.6 |
Thrombocytopenia | grade 4, 66.7% DLT |
2.25 g/m2 1 times / day multiple, intravenous MTD Dose: 2.25 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 2.25 g/m2, 1 times / day Co-administed with:: doxorubicin, i.v(45 mg/m2) Sources: Page: p.6 |
unhealthy, 45 n = 3 Health Status: unhealthy Condition: Breast cancer Age Group: 45 Sex: F Population Size: 3 Sources: Page: p.6 |
Febrile neutropenia | grade 5, 33.3% DLT, Disc. AE |
2.25 g/m2 1 times / day multiple, intravenous MTD Dose: 2.25 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 2.25 g/m2, 1 times / day Co-administed with:: doxorubicin, i.v(45 mg/m2) Sources: Page: p.6 |
unhealthy, 45 n = 3 Health Status: unhealthy Condition: Breast cancer Age Group: 45 Sex: F Population Size: 3 Sources: Page: p.6 |
Cystitis hemorrhagic | severe Disc. AE |
1.2 g/m2 1 times / day multiple, intravenous Recommended Dose: 1.2 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 1.2 g/m2, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Testicular cancer Sources: Page: p.1 |
Nephrotoxicity | severe Disc. AE |
1.2 g/m2 1 times / day multiple, intravenous Recommended Dose: 1.2 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 1.2 g/m2, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Testicular cancer Sources: Page: p.1 |
Renal failure | severe Disc. AE |
1.2 g/m2 1 times / day multiple, intravenous Recommended Dose: 1.2 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 1.2 g/m2, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Testicular cancer Sources: Page: p.1 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/9157990/ |
yes | |||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
no | ||||
poor | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
Page: 28.0 |
yes | no (co-administration study) Comment: Coadministration of ifosfamide with ketoconazole or rifampin did not produce changes inthe pharmacokinetics of the parent or metabolites that may result in an increased benefit of ifosfamidetherapy. (https://pubmed.ncbi.nlm.nih.gov/11503007/) Page: 28.0 |
||
Page: 28.0 |
yes | no (co-administration study) Comment: Coadministration of ifosfamide with ketoconazole or rifampin did not produce changes inthe pharmacokinetics of the parent or metabolites that may result in an increased benefit of ifosfamidetherapy. (https://pubmed.ncbi.nlm.nih.gov/11503007/) Page: 28.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Vinorelbine-based regimens as salvage treatment in patients with advanced non-small cell lung cancer: two parallel multicenter phase II trials. | 2001 |
|
The efficacy of combination chemotherapy including intraperitoneal cisplatinum and mitoxantrone with intravenous ifosfamide in patients with FIGO stage I C ovarian carcinoma. | 2001 |
|
Malignant mixed mullerian tumor of the ovary: report of four cases. | 2001 |
|
Carnitine protects mitochondria and removes toxic acyls from xenobiotics. | 2001 |
|
Paclitaxel by 72-hour continuous infusion followed by bolus intravenous ifosfamide or epirubicin: results of two phase I studies. | 2001 |
|
Comparison of double and triple high-dose chemotherapy with autologous blood stem cell transplantation in patients with metastatic breast cancer. | 2001 |
|
Thymic malignancies. | 2001 |
|
Salvage chemotherapy in relapsed germ cell tumors. | 2001 Apr |
|
Treatment of patients with metastatic germ cell tumors relapsing after high-dose chemotherapy. | 2001 Apr |
|
A three-drug regimen (gemcitabine, ifosfamide and cisplatin) for advanced non-small-cell lung cancer. | 2001 Apr |
|
Phase II study of paclitaxel, ifosfamide, and carboplatin in patients with recurrent or metastatic head and neck squamous cell carcinoma. | 2001 Apr 1 |
|
The current status of docetaxel for advanced non-small cell lung cancer. | 2001 Feb |
|
Phase II study of a high-dose ifosfamide-based chemotherapy regimen with growth factor rescue in recurrent aggressive NHL. High response rates and limited toxicity, but limited impact on long-term survival. | 2001 Feb |
|
PBPC mobilization with paclitaxel, ifosfamide, and G-CSF with or without amifostine: results of a prospective randomized trial. | 2001 Feb |
|
A comparison of methods of loco-regional chemotherapy combined with systemic chemotherapy as neo-adjuvant treatment of osteosarcoma of the extremity. | 2001 Feb |
|
Neoadjuvant chemotherapy for high grade osteosarcoma of the extremities: long-term results for patients treated according to the Rizzoli IOR/OS-3b protocol. | 2001 Feb |
|
Absence of major peripheral neuropathy in a phase II trial of ifosfamide with vinorelbine in patients with ovarian cancer previously treated with platinum and paclitaxel. | 2001 Feb |
|
Treatment of mandibular malignant fibrous histiocytoma during pregnancy. | 2001 Feb |
|
[Is it useful to perform a (67)gallium scintigraphy in the follow-up of patients with gastric lymphoma?]. | 2001 Feb |
|
Combination chemotherapy in patients with malignant pleural effusions from non-small cell lung cancer : cisplatin, ifosfamide, and irinotecan with recombinant human granulocyte colony-stimulating factor support. | 2001 Feb |
|
Adult Gaucher disease in association with primary malignant bone tumors. | 2001 Feb 1 |
|
A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model. | 2001 Feb 1 |
|
Use of hematopoietic progenitors in whole blood to support dose-dense chemotherapy: a randomized phase II trial in small-cell lung cancer patients. | 2001 Feb 1 |
|
A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplantation. | 2001 Feb 2 |
|
The prognostic value of etoposide area under the curve (AUC) at first chemotherapy cycle in small cell lung cancer patients: a multicenter study of the groupe Lyon-Saint-Etienne d'Oncologie Thoracique (GLOT). | 2001 Feb-Mar |
|
[Prostatic angiosarcoma: report of a new case]. | 2001 Jan |
|
Clinical pharmacokinetics and pharmacodynamics of ifosfamide and its metabolites. | 2001 Jan |
|
Malignant rhabdoid tumour of the uterine cervix. | 2001 Jan |
|
A phase I clinical, pharmacological, and biological trial of interleukin 6 plus granulocyte-colony stimulating factor after ifosfamide, carboplatin, and etoposide in children with recurrent/refractory solid tumors: enhanced hematological responses but a high incidence of grade III/IV constitutional toxicities. | 2001 Jan |
|
Should we always choose a nonparametric test when comparing two apparently nonnormal distributions? | 2001 Jan |
|
Diffuse brachial plexopathy after interscalene blockade in a patient receiving cisplatin chemotherapy: the pharmacologic double crush syndrome. | 2001 Jan |
|
Carboplatin/ifosfamide window therapy for osteosarcoma: results of the St Jude Children's Research Hospital OS-91 trial. | 2001 Jan 1 |
|
Phase II study of paclitaxel, ifosfamide, and cisplatin as second-line treatment in relapsed small-cell lung cancer. | 2001 Jan 1 |
|
Salvage treatment with paclitaxel, ifosfamide, and cisplatin plus high-dose carboplatin, etoposide, and thiotepa followed by autologous stem-cell rescue in patients with relapsed or refractory germ cell cancer. | 2001 Jan 1 |
|
Long-term stent implantation in a case of relapsing intrathoracic Ewing-sarcoma. | 2001 Jan 15 |
|
A randomised phase II study on neo-adjuvant chemotherapy for 'high-risk' adult soft-tissue sarcoma. | 2001 Jun |
|
Importance of surgery as salvage treatment after high dose chemotherapy failure in germ cell tumors. | 2001 Jun |
|
Immunoglobulin D myeloma presenting as an extraosseous soft tissue tumor. | 2001 Mar |
|
[Surgical treatment of non-small cell lung cancer with mediastinal node invasion. A retrospective study]. | 2001 Mar |
|
Primary breast tumor levels of suspected molecular determinants of cellular sensitivity to cyclophosphamide, ifosfamide, and certain other anticancer agents as predictors of paired metastatic tumor levels of these determinants. Rational individualization of cancer chemotherapeutic regimens. | 2001 Mar |
|
A phase II study of dose-intense ifosfamide plus epirubicin with hematopoietic growth factors for the treatment of patients with advanced soft tissue sarcomas; a novel sequential schedule. | 2001 Mar |
|
Intrasellar rhabdomyosarcoma: case report. | 2001 Mar |
|
[A case of primary malignant hemangiopericytoma of the lung with marked response to combination chemotherapy with cisplatin, ifosfamide and gemcitabine]. | 2001 Mar |
|
Phase I trial of ifosfamide and 24-h infusional paclitaxel in pelvic malignancies: a Gynecologic Oncology Group study. | 2001 Mar |
|
Metastatic osteosarcoma to the liver after treatment for synovial sarcoma: a case report. | 2001 Mar |
|
Tumor oxygenation after radiotherapy, chemotherapy, and/or hyperthermia predicts tumor free survival. | 2001 Mar 15 |
|
Histologic response of high-grade nonmetastatic osteosarcoma of the extremity to chemotherapy, | 2001 May |
|
Haemoperfusion combined with haemodialysis in ifosfamide intoxication. | 2001 May |
|
Topoisomerase IIalpha and other drug resistance markers in advanced non-small cell lung cancer. | 2001 May |
|
Microencapsulated cell-mediated treatment of inoperable pancreatic carcinoma. | 2001 May 19 |
Sample Use Guides
30-min infusion at a dose of 1.2 grams per m2 per day for 5 consecutive days
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1968886/
Human testicular germ cell tumour lines H 12.1 and 2102 EP were treated with ifosfamide at 50 mg kg-1 day-1.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sun Dec 18 04:13:19 UTC 2022
by
admin
on
Sun Dec 18 04:13:19 UTC 2022
|
Record UNII |
ARX5AJ985I
|
Record Status |
Validated (UNII)
|
Record Version |
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-
Download
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ARX5AJ985I
Created by
admin on Sun Dec 18 04:13:19 UTC 2022 , Edited by admin on Sun Dec 18 04:13:19 UTC 2022
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ARX5AJ985I
Created by
admin on Sun Dec 18 04:13:19 UTC 2022 , Edited by admin on Sun Dec 18 04:13:19 UTC 2022
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50892-10-9
Created by
admin on Sun Dec 18 04:13:19 UTC 2022 , Edited by admin on Sun Dec 18 04:13:19 UTC 2022
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DTXSID90308749
Created by
admin on Sun Dec 18 04:13:19 UTC 2022 , Edited by admin on Sun Dec 18 04:13:19 UTC 2022
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308171
Created by
admin on Sun Dec 18 04:13:19 UTC 2022 , Edited by admin on Sun Dec 18 04:13:19 UTC 2022
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208841
Created by
admin on Sun Dec 18 04:13:19 UTC 2022 , Edited by admin on Sun Dec 18 04:13:19 UTC 2022
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Related Record | Type | Details | ||
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METABOLITE -> PARENT |
URINE
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PRODRUG -> METABOLITE ACTIVE |
labile intermediate
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Related Record | Type | Details | ||
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ACTIVE MOIETY |