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Identification
NameCyclophosphamide
Accession NumberDB00531  (APRD00408)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [PubChem]

Structure
Thumb
Synonyms
(+-)-Cyclophosphamide
(RS)-Cyclophosphamide
2-[Bis(2-chloroethylamino)]-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide
Anhydrous cyclophosphamide
Bis(2-chloroethyl)phosphoramide cyclic propanolamide ester
Ciclofosfamida
Ciclofosfamide
Cyclophosphamid
Cyclophosphamide
Cyclophosphamide anhydrous
Cyclophosphamidum
Cytophosphane
Ledoxina
N,N-Bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide
External Identifiers
  • B 518
  • NSC 26271
  • RCRA Waste Number U058
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cyclophosphamidecapsule25 mg/1oralRoxane Laboratories, Inc.2013-09-16Not applicableUs
Cyclophosphamidecapsule50 mg/1oralAvera Mc Kennan Hospital2015-04-23Not applicableUs
Cyclophosphamidecapsule25 mg/1oralAvera Mc Kennan Hospital2015-08-18Not applicableUs
Cyclophosphamideinjection, powder, lyophilized, for solution2 g/100mLintravenous; oralBaxter Healthcare Corporation1959-11-16Not applicableUs
Cyclophosphamideinjection, powder, lyophilized, for solution1 g/50mLintravenous; oralBaxter Healthcare Corporation1959-11-16Not applicableUs
Cyclophosphamideinjection, powder, lyophilized, for solution500 mg/25mLintravenous; oralBaxter Healthcare Corporation1959-11-16Not applicableUs
Cyclophosphamidecapsule50 mg/1oralRoxane Laboratories, Inc.2013-09-16Not applicableUs
Cytoxan Pws for Inj 1000mg/vialpowder for solution1000 mgintravenousBristol Myers Squibb Canada1990-12-312008-10-17Canada
Cytoxan Pws for Inj 2000mg/vialpowder for solution2000 mgintravenousBristol Myers Squibb Canada1990-12-312008-10-17Canada
Cytoxan Tab 25mgtablet25 mgoralBristol Myers Squibb Canada1977-12-312008-11-21Canada
Cytoxan Tab 50mgtablet50 mgoralBristol Myers Squibb Canada1976-12-312009-01-22Canada
Procytox 1000mg/vialpowder for solution1000 mgintravenousBaxter Corporation2003-11-18Not applicableCanada
Procytox 2000mg/vialpowder for solution2000 mgintravenousBaxter Corporation2003-11-03Not applicableCanada
Procytox 200mg/vialpowder for solution200 mgintravenousBaxter Corporation2000-11-26Not applicableCanada
Procytox 500mg/vialpowder for solution500 mgintravenousBaxter Corporation2000-10-26Not applicableCanada
Procytox Pws 500mgpowder for solution500 mgparenteral (unspecified)Carter Horner Corp.1977-12-312000-11-17Canada
Procytox Tab 25mgtablet25 mgoralCarter Horner Corp.1973-12-312001-05-22Canada
Procytox Tab 25mgtablet25 mgoralBaxter Corporation2000-09-01Not applicableCanada
Procytox Tab 50mgtablet50 mgoralBaxter Corporation2000-08-22Not applicableCanada
Procytox Tablets 50mgtablet50 mgoralCarter Horner Corp.1959-12-312001-05-22Canada
Procytox Vial 1000mgpowder for solution1 gintravenousCarter Horner Corp.1966-12-312001-05-22Canada
Procytox Vial 200mgpowder for solution200 mgintravenousCarter Horner Corp.1959-12-312000-11-26Canada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cyclophosphamideinjection, powder, for solution2 g/100mLintravenous; oralBaxter Healthcare Corporation2008-05-21Not applicableUs
Cyclophosphamideinjection, powder, for solution1 g/50mLintravenous; oralBaxter Healthcare Corporation2008-05-21Not applicableUs
Cyclophosphamidetablet25 mg/1oralRoxane Laboratories, Inc.1999-08-17Not applicableUs
Cyclophosphamideinjection, powder, for solution1 g/50mLintravenous; oralBaxter Healthcare Corporation2008-05-21Not applicableUs
Cyclophosphamideinjection, powder, for solution1 g/50mLintravenous; oralBaxter Healthcare Corporation2008-05-21Not applicableUs
Cyclophosphamideinjection, powder, for solution500 mg/25mLintravenous; oralBaxter Healthcare Corporation2008-05-21Not applicableUs
Cyclophosphamideinjection, powder, for solution500 mg/25mLintravenous; oralBaxter Healthcare Corporation2008-05-21Not applicableUs
Cyclophosphamideinjection, powder, for solution2 g/100mLintravenous; oralSandoz Inc.2014-10-31Not applicableUs
Cyclophosphamideinjection, powder, for solution2 g/100mLintravenous; oralBaxter Healthcare Corporation2008-05-21Not applicableUs
Cyclophosphamideinjection, powder, for solution1 g/50mLintravenous; oralSandoz Inc.2014-10-31Not applicableUs
Cyclophosphamidetablet25 mg/1oralPhysicians Total Care, Inc.1999-08-17Not applicableUs
Cyclophosphamideinjection, powder, for solution1 g/50mLintravenous; oralBaxter Healthcare Corporation2008-05-21Not applicableUs
Cyclophosphamideinjection, powder, for solution500 mg/25mLintravenous; oralSandoz Inc.2014-10-31Not applicableUs
Cyclophosphamidetablet50 mg/1oralPhysicians Total Care, Inc.1999-08-17Not applicableUs
Cyclophosphamideinjection, powder, for solution500 mg/25mLintravenous; oralBaxter Healthcare Corporation2008-05-21Not applicableUs
Cyclophosphamideinjection, powder, for solution500 mg/25mLintravenous; oralBaxter Healthcare Corporation2008-05-21Not applicableUs
Cyclophosphamidetablet50 mg/1oralRoxane Laboratories, Inc.1999-08-17Not applicableUs
Cyclophosphamideinjection, powder, for solution2 g/100mLintravenous; oralBaxter Healthcare Corporation2008-05-21Not applicableUs
Cyclophosphamideinjection, powder, for solution2 g/100mLintravenous; oralBaxter Healthcare Corporation2008-05-21Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
CytoxanBristol-Myers Squibb
EndoxanActavis
NeosarNot Available
ProcytoxBaxter
RevimmuneNot Available
SendoxanBaxter
Brand mixtures
NameLabellerIngredients
Procytox for Injection 2000mg Pws IVCarter Horner Corp.
Salts
Name/CASStructureProperties
Cyclophosphamide monohydrate
6055-19-2
Thumb
  • InChI Key: PWOQRKCAHTVFLB-UHFFFAOYSA-N
  • Monoisotopic Mass: 278.0353848
  • Average Mass: 279.1
DBSALT001814
Categories
UNII6UXW23996M
CAS number50-18-0
WeightAverage: 261.086
Monoisotopic: 260.02481966
Chemical FormulaC7H15Cl2N2O2P
InChI KeyInChIKey=CMSMOCZEIVJLDB-UHFFFAOYSA-N
InChI
InChI=1S/C7H15Cl2N2O2P/c8-2-5-11(6-3-9)14(12)10-4-1-7-13-14/h1-7H2,(H,10,12)
IUPAC Name
2-[bis(2-chloroethyl)amino]-1,3,2λ⁵-oxazaphosphinan-2-one
SMILES
ClCCN(CCCl)P1(=O)NCCCO1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as nitrogen mustard compounds. These are compounds having two beta-haloalkyl groups bound to a nitrogen atom.
KingdomOrganic compounds
Super ClassOrganonitrogen compounds
ClassNitrogen mustard compounds
Sub ClassNot Available
Direct ParentNitrogen mustard compounds
Alternative Parents
Substituents
  • Nitrogen mustard
  • Phosphoric monoester diamide
  • Oxazaphosphinane
  • Organic phosphoric acid derivative
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organochloride
  • Organohalogen compound
  • Alkyl halide
  • Alkyl chloride
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationCyclophosphamide is indicated for the treatment of malignant lymphomas, multiple myeloma, leukemias, mycosis fungoides (advanced disease), neuroblastoma (disseminated disease), adenocarcinoma of the ovary, retinoblastoma, and carcinoma of the breast. It is also indicated for the treatment of biopsy-proven minimal change nephrotic syndrome in pediatric patients.
PharmacodynamicsCyclophosphamide is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.
Mechanism of actionAlkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations.
Related Articles
AbsorptionAfter oral administration, peak concentrations occur at one hour.
Volume of distribution

30-50 L

Protein binding20% of cyclophosphamide is protein bound with no dose dependent changes. Some metabolites are protein bound to an extent greater than 60%.
Metabolism

Metabolism and activation occurs at the liver. 75% of the drug is activated by cytochrome P450 isoforms, CYP2A6, 2B6, 3A4, 3A5, 2C9, 2C18, and 2C19. The CYP2B6 isoform is the enzyme with the highest 4-hydroxylase activity. Cyclophosphamide undergoes activation to eventually form active metabolites, phosphoramide mustard and acrolein. Cyclophosphamide appears to induce its own metabolism which results in an overall increase in clearance, increased formation of 4-hydroxyl metabolites, and shortened t1/2 values following repeated administration.

SubstrateEnzymesProduct
Cyclophosphamide
4-HydroxycyclophosphamideDetails
Cyclophosphamide
Dechloroethyl cyclophosphamideDetails
Cyclophosphamide
ChloroacetaldehydeDetails
4-Hydroxycyclophosphamide
4-KetocyclophosphamideDetails
4-Hydroxycyclophosphamide
Not Available
AldophosphamideDetails
Aldophosphamide
Not Available
CarboxyphosphamideDetails
Aldophosphamide
AlcophosphamideDetails
Aldophosphamide
CarboxyphosphamideDetails
Carboxyphosphamide
Not Available
Nornitrogen mustardDetails
Aldophosphamide
Not Available
AcroleinDetails
Acrolein
Acrylic AcidDetails
Aldophosphamide
Not Available
Phosphoramide MustardDetails
Phosphoramide Mustard
Not Available
Phosphoramide AziridiniumDetails
Route of eliminationCyclophosphamide is eliminated primarily in the form of metabolites. 10-20% is excreted unchanged in the urine and 4% is excreted in the bile following IV administration.
Half life3-12 hours
Clearance

Total body clearance = 63 ± 7.6 L/kg.

ToxicityAdverse reactions reported most often include neutropenia, febrile neutropenia, fever, alopecia, nausea, vomiting, and diarrhea.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Cyclophosphamide Action PathwayDrug actionSMP00447
Cyclophosphamide Metabolism PathwayDrug metabolismSMP00604
SNP Mediated Effects
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeEffectReference(s)
Cytochrome P450 3A4
Gene symbol: CYP3A4
UniProt: P08684
rs2740574 CYP3A4 *1BG AllelleDecreased activation of cyclophosphamide most likely contributing to worse disease free survival in adjuvant chemotherapy for node-positive breast cancer20459744
Cytochrome P450 2B6
Gene symbol: CYP2B6
UniProt: P20813
Not AvailableCYP2B6*1GC AllelleDecreased activation of cyclophosphamide contributing to less adverse reactions (leukocytopenia)17502835
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9722
Blood Brain Barrier+0.971
Caco-2 permeable-0.5451
P-glycoprotein substrateNon-substrate0.71
P-glycoprotein inhibitor INon-inhibitor0.779
P-glycoprotein inhibitor IINon-inhibitor0.9797
Renal organic cation transporterNon-inhibitor0.8125
CYP450 2C9 substrateNon-substrate0.7856
CYP450 2D6 substrateNon-substrate0.5884
CYP450 3A4 substrateSubstrate0.5461
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9232
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.9232
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9737
Ames testAMES toxic0.9146
CarcinogenicityNon-carcinogens0.8727
BiodegradationNot ready biodegradable0.9511
Rat acute toxicity3.3855 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.8419
hERG inhibition (predictor II)Non-inhibitor0.8735
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Baxter healthcare corp
  • Baxter healthcare corp anesthesia and critical care
  • Teva parenteral medicines inc
  • Roxane laboratories inc
Packagers
Dosage forms
FormRouteStrength
Capsuleoral25 mg/1
Capsuleoral50 mg/1
Injection, powder, for solutionintravenous; oral1 g/50mL
Injection, powder, for solutionintravenous; oral2 g/100mL
Injection, powder, for solutionintravenous; oral500 mg/25mL
Injection, powder, lyophilized, for solutionintravenous; oral1 g/50mL
Injection, powder, lyophilized, for solutionintravenous; oral2 g/100mL
Injection, powder, lyophilized, for solutionintravenous; oral500 mg/25mL
Tabletoral25 mg/1
Tabletoral50 mg/1
Powder for solutionintravenous1000 mg
Powder for solutionintravenous2000 mg
Powder for solutionintravenous200 mg
Powder for solutionintravenous500 mg
Powder for solutionintravenous
Powder for solutionparenteral (unspecified)500 mg
Tabletoral25 mg
Tabletoral50 mg
Powder for solutionintravenous1 g
Prices
Unit descriptionCostUnit
Cyclophosphamide 500 mg vial37.76USD vial
Cyclophosphamide 100% powder33.66USD g
Cytoxan 500 mg vial15.25USD vial
Cytoxan 50 mg tablet4.14USD tablet
Cyclophosphamide 50 mg tablet3.92USD tablet
Cytoxan 25 mg tablet2.26USD tablet
Cyclophosphamide 25 mg tablet2.09USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point48-49Arnold, H., Brock, N. and Bourseaux, F.; U S . Patent 3,018,302; January 23,1962; assigned to Asta-Werke A.G. Chemische Fabrik (W. Germany).
water solubilitySoluble. 1-5 g/100 mL at 23 °CNot Available
logP0.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility15.1 mg/mLALOGPS
logP0.76ALOGPS
logP0.097ChemAxon
logS-1.2ALOGPS
pKa (Strongest Acidic)12.78ChemAxon
pKa (Strongest Basic)-0.57ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area41.57 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity58.48 m3·mol-1ChemAxon
Polarizability23.72 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (9.91 KB)
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
MSMass Spectrum (Electron Ionization)splash10-08fr-9470000000-53f4a8ff83c415492e03View in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR13C NMR SpectrumNot Available
References
Synthesis Reference

Riccardo Dalla-Favera, Alessandro Massimo Gianni, “Retroviral vector capable of transducing the aldehyde dehydrogenase-1 gene and making cells resistant to the chemotherapeutic agent cyclophosphamide and its derivatives and analogs.” U.S. Patent US6268138, issued March, 1999.

US6268138
General References
  1. Brock N: The history of the oxazaphosphorine cytostatics. Cancer. 1996 Aug 1;78(3):542-7. [PubMed:8697402 ]
  2. Brock N: Oxazaphosphorine cytostatics: past-present-future. Seventh Cain Memorial Award lecture. Cancer Res. 1989 Jan 1;49(1):1-7. [PubMed:2491747 ]
External Links
ATC CodesL01AA01
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (76.1 KB)
Interactions
Drug Interactions
Drug
AllopurinolThe risk or severity of adverse effects can be increased when Allopurinol is combined with Cyclophosphamide.
AmiodaroneThe risk or severity of adverse effects can be increased when Cyclophosphamide is combined with Amiodarone.
AtazanavirThe risk or severity of adverse effects can be increased when Atazanavir is combined with Cyclophosphamide.
AzathioprineAzathioprine may increase the hepatotoxic activities of Cyclophosphamide.
BatimastatThe risk or severity of adverse effects can be increased when Batimastat is combined with Cyclophosphamide.
BelimumabThe risk or severity of adverse effects can be increased when Belimumab is combined with Cyclophosphamide.
ChlorothiazideThe risk or severity of adverse effects can be increased when Chlorothiazide is combined with Cyclophosphamide.
ChlorthalidoneThe risk or severity of adverse effects can be increased when Chlorthalidone is combined with Cyclophosphamide.
ClozapineThe risk or severity of adverse effects can be increased when Cyclophosphamide is combined with Clozapine.
CyclosporineCyclophosphamide may increase the immunosuppressive activities of Cyclosporine.
DabrafenibThe serum concentration of Cyclophosphamide can be decreased when it is combined with Dabrafenib.
DarunavirThe risk or severity of adverse effects can be increased when Darunavir is combined with Cyclophosphamide.
DaunorubicinCyclophosphamide may increase the cardiotoxic activities of Daunorubicin.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Cyclophosphamide.
DoxorubicinCyclophosphamide may increase the cardiotoxic activities of Doxorubicin.
EpirubicinCyclophosphamide may increase the cardiotoxic activities of Epirubicin.
EtanerceptThe risk or severity of adverse effects can be increased when Etanercept is combined with Cyclophosphamide.
FilgrastimThe risk or severity of adverse effects can be increased when Filgrastim is combined with Cyclophosphamide.
Filgrastim-sndzThe risk or severity of adverse effects can be increased when Filgrastim-sndz is combined with Cyclophosphamide.
FosamprenavirThe risk or severity of adverse effects can be increased when Fosamprenavir is combined with Cyclophosphamide.
HydrochlorothiazideThe risk or severity of adverse effects can be increased when Hydrochlorothiazide is combined with Cyclophosphamide.
IdarubicinCyclophosphamide may increase the cardiotoxic activities of Idarubicin.
IndapamideThe risk or severity of adverse effects can be increased when Indapamide is combined with Cyclophosphamide.
IndinavirThe risk or severity of adverse effects can be increased when Indinavir is combined with Cyclophosphamide.
IsoflurophateThe risk or severity of adverse effects can be increased when Isoflurophate is combined with Cyclophosphamide.
LeflunomideThe risk or severity of adverse effects can be increased when Cyclophosphamide is combined with Leflunomide.
LumacaftorThe serum concentration of Cyclophosphamide can be decreased when it is combined with Lumacaftor.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Cyclophosphamide.
MethyclothiazideThe risk or severity of adverse effects can be increased when Methyclothiazide is combined with Cyclophosphamide.
MetolazoneThe risk or severity of adverse effects can be increased when Metolazone is combined with Cyclophosphamide.
MitoxantroneCyclophosphamide may increase the cardiotoxic activities of Mitoxantrone.
NatalizumabThe risk or severity of adverse effects can be increased when Cyclophosphamide is combined with Natalizumab.
NelfinavirThe risk or severity of adverse effects can be increased when Nelfinavir is combined with Cyclophosphamide.
NevirapineThe metabolism of Cyclophosphamide can be increased when combined with Nevirapine.
PentostatinPentostatin may increase the cardiotoxic activities of Cyclophosphamide.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Cyclophosphamide.
QuazepamThe serum concentration of Cyclophosphamide can be increased when it is combined with Quazepam.
RitonavirThe risk or severity of adverse effects can be increased when Ritonavir is combined with Cyclophosphamide.
RoflumilastRoflumilast may increase the immunosuppressive activities of Cyclophosphamide.
SaquinavirThe risk or severity of adverse effects can be increased when Saquinavir is combined with Cyclophosphamide.
SargramostimThe risk or severity of adverse effects can be increased when Cyclophosphamide is combined with Sargramostim.
SimeprevirThe risk or severity of adverse effects can be increased when Simeprevir is combined with Cyclophosphamide.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Cyclophosphamide.
SuccinylcholineThe serum concentration of Succinylcholine can be increased when it is combined with Cyclophosphamide.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Cyclophosphamide.
TiclopidineThe metabolism of Cyclophosphamide can be decreased when combined with Ticlopidine.
TipranavirThe risk or severity of adverse effects can be increased when Tipranavir is combined with Cyclophosphamide.
TofacitinibCyclophosphamide may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Cyclophosphamide.
TrichlormethiazideThe risk or severity of adverse effects can be increased when Trichlormethiazide is combined with Cyclophosphamide.
Food Interactions
  • Drink liberally- 2 to 3 liters/day.
  • Take with food to reduce irritation.

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
cross-linking/alkylation
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Khan O, Middleton MR: The therapeutic potential of O6-alkylguanine DNA alkyltransferase inhibitors. Expert Opin Investig Drugs. 2007 Oct;16(10):1573-84. [PubMed:17922622 ]
  4. Schmidt E, Tony HP, Brocker EB, Kneitz C: Sun-induced life-threatening lupus nephritis. Ann N Y Acad Sci. 2007 Jun;1108:35-40. [PubMed:17893968 ]
  5. Zhang QH, Wu CF, Duan L, Yang JY: Protective effects of total saponins from stem and leaf of Panax ginseng against cyclophosphamide-induced genotoxicity and apoptosis in mouse bone marrow cells and peripheral lymphocyte cells. Food Chem Toxicol. 2008 Jan;46(1):293-302. Epub 2007 Aug 23. [PubMed:17904265 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinducer
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular Weight:
56277.81 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
  2. Preiss R, Schmidt R, Baumann F, Hanschmann H, Hauss J, Geissler F, Pahlig H, Ratzewiss B: Measurement of 4-hydroxylation of ifosfamide in human liver microsomes using the estimation of free and protein-bound acrolein and codetermination of keto- and carboxyifosfamide. J Cancer Res Clin Oncol. 2002 Jul;128(7):385-92. Epub 2002 Jun 11. [PubMed:12136253 ]
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  4. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinducer
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitorinducer
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
  2. Preiss R, Schmidt R, Baumann F, Hanschmann H, Hauss J, Geissler F, Pahlig H, Ratzewiss B: Measurement of 4-hydroxylation of ifosfamide in human liver microsomes using the estimation of free and protein-bound acrolein and codetermination of keto- and carboxyifosfamide. J Cancer Res Clin Oncol. 2002 Jul;128(7):385-92. Epub 2002 Jun 11. [PubMed:12136253 ]
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.
Gene Name:
CYP2A6
Uniprot ID:
P11509
Molecular Weight:
56501.005 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP2C18
Uniprot ID:
P33260
Molecular Weight:
55710.075 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinducer
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular Weight:
55824.275 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A7
Uniprot ID:
P24462
Molecular Weight:
57525.03 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57108.065 Da
References
  1. Ekhart C, Doodeman VD, Rodenhuis S, Smits PH, Beijnen JH, Huitema AD: 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. Pharmacogenet Genomics. 2008 Jun;18(6):515-23. doi: 10.1097/FPC.0b013e3282fc9766. [PubMed:18496131 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
References
  1. Wang E, Lew K, Barecki M, Casciano CN, Clement RP, Johnson WW: Quantitative distinctions of active site molecular recognition by P-glycoprotein and cytochrome P450 3A4. Chem Res Toxicol. 2001 Dec;14(12):1596-603. [PubMed:11743742 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23