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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

1988
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
346 μM
3 g/m² single, intravenous
dose: 3 g/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
IFOSFAMIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
200 μM
1.5 g/m² single, oral
dose: 1.5 g/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
IFOSFAMIDE plasma
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 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2197 mM × h
3 g/m² single, intravenous
dose: 3 g/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
IFOSFAMIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1360 μM × h
1.5 g/m² single, oral
dose: 1.5 g/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
IFOSFAMIDE plasma
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 plasma
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 plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
4.33 h
3 g/m² single, intravenous
dose: 3 g/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
IFOSFAMIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
5 h
1.5 g/m² single, oral
dose: 1.5 g/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
IFOSFAMIDE plasma
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 plasma
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 plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
100%
unknown
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
MTD
Dose: 18 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 18 g/m2, 1 times / day
Sources:
unhealthy, 45
Health Status: unhealthy
Age Group: 45
Sex: M+F
Sources:
DLT: Neutropenia, Infection...
Dose limiting toxicities:
Neutropenia (grade 4, 83.3%)
Infection (severe, 33.3%)
Thrombocytopenia (grade 4, 66.7%)
Sources:
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
Sources:
unhealthy, 45
Health Status: unhealthy
Age Group: 45
Sex: F
Sources:
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:
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:
unhealthy
Disc. AE: Nephrotoxicity, Renal failure...
AEs leading to
discontinuation/dose reduction:
Nephrotoxicity (severe)
Renal failure (severe)
Cystitis hemorrhagic (severe)
Sources:
AEs

AEs

AESignificanceDosePopulation
Thrombocytopenia grade 4, 66.7%
DLT
18 g/m2 1 times / day multiple, intravenous
MTD
Dose: 18 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 18 g/m2, 1 times / day
Sources:
unhealthy, 45
Health Status: unhealthy
Age Group: 45
Sex: M+F
Sources:
Neutropenia grade 4, 83.3%
DLT
18 g/m2 1 times / day multiple, intravenous
MTD
Dose: 18 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 18 g/m2, 1 times / day
Sources:
unhealthy, 45
Health Status: unhealthy
Age Group: 45
Sex: M+F
Sources:
Infection severe, 33.3%
DLT
18 g/m2 1 times / day multiple, intravenous
MTD
Dose: 18 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 18 g/m2, 1 times / day
Sources:
unhealthy, 45
Health Status: unhealthy
Age Group: 45
Sex: M+F
Sources:
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
Sources:
unhealthy, 45
Health Status: unhealthy
Age Group: 45
Sex: F
Sources:
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
Sources:
unhealthy, 45
Health Status: unhealthy
Age Group: 45
Sex: F
Sources:
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
Sources:
unhealthy, 45
Health Status: unhealthy
Age Group: 45
Sex: F
Sources:
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
Sources:
unhealthy, 45
Health Status: unhealthy
Age Group: 45
Sex: F
Sources:
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:
unhealthy
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:
unhealthy
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:
unhealthy
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
Intratumoral injection of encapsulated cells producing an oxazaphosphorine activating cytochrome P450 for targeted chemotherapy.
1998
Prospective evaluation of high-dose ifosfamide-related nephrotoxicity in young adult patients with recurrent osteosarcoma previously treated with cisplatin, methotrexate and standard-dose ifosfamide.
1999 Jan
Injection of encapsulated cells producing an ifosfamide-activating cytochrome P450 for targeted chemotherapy to pancreatic tumors.
1999 Jun 30
Development of ifosfamide-induced nephrotoxicity: prospective follow-up in 75 patients.
1999 Mar
Risk factors for long-term outcome of ifosfamide-induced nephrotoxicity in children.
1999 May
Methylene blue in the treatment and prevention of ifosfamide-induced encephalopathy: report of 12 cases and a review of the literature.
2000 Jan
Subacute central nervous system degeneration in a child: an unusual manifestation of ifosfamide intoxication.
2000 Jul
Distinctive potentiating effects of cisplatin and/or ifosfamide combined with etoposide in human small cell lung carcinoma xenografts.
2000 May
Two episodes of ifosfamide-related neurotoxicity in the same patient following different schedules and doses of the drug. A case report.
2000 Nov-Dec
A phase II study of weekly alternating chemotherapy in extensive-stage small cell lung cancer.
2001
Comparison of double and triple high-dose chemotherapy with autologous blood stem cell transplantation in patients with metastatic breast cancer.
2001
[Post-operative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: results of German prospective randomised trial HIT'91].
2001 Apr
[Pigmented villonodular synovitis: apropos of 3 cases].
2001 Apr
The current status of docetaxel for advanced non-small cell lung cancer.
2001 Feb
Sustained response of sarcomatoid renal-cell carcinoma to MAID chemotherapy: case report and review of the literature.
2001 Feb
Selective use of whole-lung irradiation for patients with Ewing sarcoma family tumors and pulmonary metastases at the time of diagnosis.
2001 Feb
[Is it useful to perform a (67)gallium scintigraphy in the follow-up of patients with gastric lymphoma?].
2001 Feb
Adult Gaucher disease in association with primary malignant bone tumors.
2001 Feb 1
[Prostatic angiosarcoma: report of a new case].
2001 Jan
Anticancer drug-induced kidney disorders.
2001 Jan
Should we always choose a nonparametric test when comparing two apparently nonnormal distributions?
2001 Jan
Docetaxel and ifosfamide as second line treatment for patients with advanced or metastatic urothelial cancer after failure of platinum chemotherapy: a phase 2 study.
2001 Jan
Carboplatin/ifosfamide window therapy for osteosarcoma: results of the St Jude Children's Research Hospital OS-91 trial.
2001 Jan 1
A randomized trial of amifostine as a cytoprotective agent in patients receiving chemotherapy for small cell lung cancer.
2001 Jan 5
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
Gemcitabine for the treatment of non-small-cell lung cancer.
2001 Mar
Intrasellar rhabdomyosarcoma: case report.
2001 Mar
Topoisomerase IIalpha and other drug resistance markers in advanced non-small cell lung cancer.
2001 May
A novel alkylating agent, glufosfamide, enhances the activity of gemcitabine in vitro and in vivo.
2007 Aug
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 Mon Mar 31 23:05:48 GMT 2025
Edited
by admin
on Mon Mar 31 23:05:48 GMT 2025
Record UNII
ARX5AJ985I
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ASTA-6569
Preferred Name English
4-HYDROXYIFOSFAMIDE
Common 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 Mon Mar 31 23:05:48 GMT 2025 , Edited by admin on Mon Mar 31 23:05:48 GMT 2025
PRIMARY
CAS
50892-10-9
Created by admin on Mon Mar 31 23:05:48 GMT 2025 , Edited by admin on Mon Mar 31 23:05:48 GMT 2025
PRIMARY
EPA CompTox
DTXSID90308749
Created by admin on Mon Mar 31 23:05:48 GMT 2025 , Edited by admin on Mon Mar 31 23:05:48 GMT 2025
PRIMARY
PUBCHEM
308171
Created by admin on Mon Mar 31 23:05:48 GMT 2025 , Edited by admin on Mon Mar 31 23:05:48 GMT 2025
PRIMARY
NSC
208841
Created by admin on Mon Mar 31 23:05:48 GMT 2025 , Edited by admin on Mon Mar 31 23:05:48 GMT 2025
PRIMARY
Related Record Type Details
PRODRUG -> METABOLITE ACTIVE
METABOLITE -> PARENT
URINE
PRODRUG -> METABOLITE ACTIVE
Related Record Type Details
ACTIVE MOIETY