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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
Structure of 4-HYDROXYIFOSFAMIDE

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)

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 ( + / - )

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

Curator's Comment: Ifosfamide crosses the blood-brain barrier and may cause encephalopathy.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
IFEX

Approved Use

Ifosfamide 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 Date

5.9944318E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
200 μM
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
1360 μM × h
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
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
5 h
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
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
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

Funbound

ValueDoseCo-administeredAnalytePopulation
100%
IFOSFAMIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse 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%)
Infection (severe, 33.3%)
Thrombocytopenia (grade 4, 66.7%)
Sources: Page: p.1090
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%)
Febrile neutropenia (grade 5, 33.3%)
Thrombocytopenia (grade 4, 66.7%)
Anemia (grade 4, 66.7%)
Sources: Page: p.6
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)
Renal failure (severe)
Cystitis hemorrhagic (severe)
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
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

Overview

CYP3A4CYP2C9CYP2D6hERG



Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
poor
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
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
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

PubMed

TitleDatePubMed
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
Patents

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
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 Sun Dec 18 04:13:19 UTC 2022
Edited
by admin
on Sun Dec 18 04:13:19 UTC 2022
Record UNII
ARX5AJ985I
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
4-HYDROXYIFOSFAMIDE
Common Name English
ASTA-6569
Brand Name English
NSC-208841
Code English
2H-1,3,2-OXAZAPHOSPHORIN-4-OL, 3-(2-CHLOROETHYL)-2-((2-CHLOROETHYL)AMINO)TETRAHYDRO-, 2-OXIDE
Systematic Name English
4-HYDROXYISOPHOSPHAMIDE
Common Name English
Code System Code Type Description
FDA UNII
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
PRIMARY
DAILYMED
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
PRIMARY
CAS
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
PRIMARY
EPA CompTox
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
PRIMARY
PUBCHEM
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
PRIMARY
NSC
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
PRIMARY
Related Record Type Details
METABOLITE -> PARENT
URINE
PRODRUG -> METABOLITE ACTIVE
labile intermediate
Related Record Type Details
ACTIVE MOIETY