Details of the Drug

General Information of Drug (ID: DMOQVU9)

Drug Name

Hydroxyurea

Synonyms

Biosupressin; Droxia; Hidrix; Hidroxicarbamida; Hydrea; Hydreia; Hydroxicarbamidum; Hydroxyaminomethanamide; Hydroxycarbamid; Hydroxycarbamide; Hydroxycarbamidum; Hydroxycarbamine; Hydroxyharnstoff; Hydroxylurea; Hydura; Hydurea; Idrossicarbamide; Litaler; Litalir; Mylocel; NHY; Oncocarbide; Oxyurea; Siklos; Carbamide oxide; Carbamohydroxamic acid; Carbamohydroximic acid; Carbamohydroxyamic acid; Carbamoyl oxime; Carbamyl hydroxamate; Carrbamoyl Oxime; Hydroxyharnstoff [German]; Idrossicarbamide [DCIT]; H 8627; SK 22591; SQ 1089; DRG-0253; Droxia (TM); Droxia (TN); HYDREA (TN); HYDROXY-UREA; Hidroxicarbamida [INN-Spanish]; Hydrea (TM); Hydroxycarbamidum [INN-Latin]; Hydroxyurea (D4); Hydroxyurea (USP); Hydroxyurea [USAN:BAN]; Hydroxyurea(d4); N-Carbamoylhydroxylamine; N-HYDROXY UREA; N-Hydroxymocovina; N-Hydroxymocovina [Czech]; N-Hydroxyurea; Onco-carbide; SQ-1089; Tetratogen: inhibits ribonucleoside diphosphate reductase; Hydroxycarbamide (JAN/INN); N-(Aminocarbonyl) Hydroxyamine; Hydrea, Biosupressin, Cytodrox, Hydroxyurea; S-phase/G-1 interface inhibitor; 1-HYDROXYUREA

Indication

Disease Entry	ICD 11	Status	REF
Chronic myelogenous leukaemia	2A20.0	Approved	[1], [2]

Therapeutic Class

Anticancer Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

76.055

Topological Polar Surface Area (xlogp)

-1.8

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption: The drug is well absorbed from the gastrointestinal tract [3]
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [4]
Bioavailability: 79% of drug becomes completely available to its intended biological destination(s) [5]
Clearance: The drug present in the plasma can be removed from the body at the rate of 1.5 mL/min/kg [6]
Elimination: 80% of drug is excreted from urine in the unchanged form [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 3 - 4 hours [6]
Metabolism: The drug is metabolized via the hepatic [3]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 1502.57324 micromolar/kg/day [7]
Unbound Fraction: The unbound fraction of drug in plasma is 1% [6]
Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.52 L/kg [6]
Water Solubility: The ability of drug to dissolve in water is measured as 50 mg/mL [4]

Chemical Identifiers

Formula: CH4N2O2
IUPAC Name: hydroxyurea
Canonical SMILES: C(=O)(N)NO
InChI: InChI=1S/CH4N2O2/c2-1(4)3-5/h5H,(H3,2,3,4)
InChIKey: VSNHCAURESNICA-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 3657
ChEBI ID: CHEBI:44423
CAS Number: 127-07-1
DrugBank ID: DB01005
TTD ID: D07CWD
VARIDT ID: DR01177
ACDINA ID: D00317

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Ribonucleoside-diphosphate reductase M2 (RRM2)	TTBWDI0	RIR2_HUMAN	Modulator	[8]

------------------------------------------------------------------------------------

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[9]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[9]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[9]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[10]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Chronic myelogenous leukaemia

ICD Disease Classification

2A20.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Ribonucleoside-diphosphate reductase M2 (RRM2)	DTT	RRM2	1.66E-04	2.66	1.68
P-glycoprotein 1 (ABCB1)	DTP	P-GP	2.74E-01	-2.19E-01	-3.03E-01
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTP	OATP1A2	2.63E-02	-2.27E-01	-1.21E+00
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DTP	OATP1B3	2.10E-05	-2.39E-02	-3.15E-02
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DTP	OATP1B1	9.07E-02	-9.94E-02	-5.12E-01

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Hydroxyurea

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive myelosuppressive effects by the combination of Hydroxyurea and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[47]
-----------

Coadministration of a Drug Treating the Disease Different from Hydroxyurea (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Roflumilast	DMPGHY8	Moderate	Additive immunosuppressive effects by the combination of Hydroxyurea and Roflumilast.	Asthma [CA23]	[48]
Ofloxacin	DM0VQN3	Minor	Decreased absorption of Hydroxyurea due to intestinal mucosa variation caused by Ofloxacin.	Bacterial infection [1A00-1C4Z]	[49]
Sparfloxacin	DMB4HCT	Minor	Decreased absorption of Hydroxyurea due to intestinal mucosa variation caused by Sparfloxacin.	Bacterial infection [1A00-1C4Z]	[49]
Gemifloxacin	DMHT34O	Minor	Decreased absorption of Hydroxyurea due to intestinal mucosa variation caused by Gemifloxacin.	Bacterial infection [1A00-1C4Z]	[49]
Norfloxacin	DMIZ6W2	Minor	Decreased absorption of Hydroxyurea due to intestinal mucosa variation caused by Norfloxacin.	Bacterial infection [1A00-1C4Z]	[49]
ABT-492	DMJFD2I	Minor	Decreased absorption of Hydroxyurea due to intestinal mucosa variation caused by ABT-492.	Bacterial infection [1A00-1C4Z]	[49]
Levofloxacin	DMS60RB	Minor	Decreased absorption of Hydroxyurea due to intestinal mucosa variation caused by Levofloxacin.	Bacterial infection [1A00-1C4Z]	[49]
Sulfinpyrazone	DMEV954	Moderate	Antagonize the effect of Hydroxyurea when combined with Sulfinpyrazone.	Gout [FA25]	[50]
Teriflunomide	DMQ2FKJ	Major	Additive myelosuppressive effects by the combination of Hydroxyurea and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[51]
Probenecid	DMMFWOJ	Moderate	Antagonize the effect of Hydroxyurea when combined with Probenecid.	Inborn purine/pyrimidine/nucleotide metabolism error [5C55]	[50]
Denosumab	DMNI0KO	Moderate	Additive myelosuppressive effects by the combination of Hydroxyurea and Denosumab.	Low bone mass disorder [FB83]	[52]
Thalidomide	DM70BU5	Major	Additive thrombogenic effects by the combination of Hydroxyurea and Thalidomide.	Multiple myeloma [2A83]	[53]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Hydroxyurea and Tecfidera.	Multiple sclerosis [8A40]	[54]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Hydroxyurea and Siponimod.	Multiple sclerosis [8A40]	[50]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of Hydroxyurea and Fingolimod.	Multiple sclerosis [8A40]	[55]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Hydroxyurea and Ozanimod.	Multiple sclerosis [8A40]	[48]
Gatifloxacin	DMSL679	Minor	Decreased absorption of Hydroxyurea due to intestinal mucosa variation caused by Gatifloxacin.	Respiratory infection [CA07-CA4Z]	[49]
Canakinumab	DM8HLO5	Moderate	Additive immunosuppressive effects by the combination of Hydroxyurea and Canakinumab.	Rheumatoid arthritis [FA20]	[56]
Golimumab	DMHZV7X	Major	Additive immunosuppressive effects by the combination of Hydroxyurea and Golimumab.	Rheumatoid arthritis [FA20]	[57]
Leflunomide	DMR8ONJ	Major	Additive immunosuppressive effects by the combination of Hydroxyurea and Leflunomide.	Rheumatoid arthritis [FA20]	[51]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Hydroxyurea when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[58]
Valganciclovir	DMS2IUH	Moderate	Additive myelosuppressive effects by the combination of Hydroxyurea and Valganciclovir.	Virus infection [1A24-1D9Z]	[50]
-----------


⏷ Show the Full List of 22 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Allura red AC dye	E00338	33258	Colorant
Benzyl alcohol	E00010	244	Antimicrobial preservative; Solvent
Butylparaben	E00142	7184	Antimicrobial preservative
D&C red no. 28	E00491	6097185	Colorant
D&C red no. 33	E00261	19116	Colorant
FD&C blue no. 1	E00263	19700	Colorant
FD&C blue no. 2	E00446	2723854	Colorant
Kyselina citronova	E00014	311	Acidulant; Antioxidant; Buffering agent; Complexing agent; Flavoring agent
methylparaben	E00149	7456	Antimicrobial preservative
Propylparaben sodium	E00567	23679044	Antimicrobial preservative
Quinoline yellow WS	E00309	24671	Colorant
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Carboxymethylcellulose sodium	E00621	Not Available	Adsorbent; Binding agent; Disintegrant; Emulsifying agent; Suspending agent; Viscosity-controlling agent
Citric acid monohydrate	E00271	22230	Acidulant; Antioxidant; Buffering agent; Complexing agent; Flavoring agent
Edetate calcium disodium	E00487	6093170	Complexing agent
Eisenoxyd	E00585	56841934	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Sodium propionate	E00445	2723816	Antimicrobial preservative
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
--------------------


⏷ Show the Full List of 24 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Hydroxyurea 500 mg capsule	500 mg	Oral Capsule	Oral
Hydroxyurea 300 mg capsule	300 mg	Oral Capsule	Oral
Hydroxyurea 400 mg capsule	400 mg	Oral Capsule	Oral
Hydroxyurea 200 mg capsule	200 mg	Oral Capsule	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6822).
2	Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of psori... J Am Acad Dermatol. 2009 Sep;61(3):451-85.
3	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
4	BDDCS applied to over 900 drugs
5	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
6	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
7	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
8	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
9	Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters. Exp Hematol. 2011 Apr;39(4):446-56.
10	Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
11	Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
12	MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
13	Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
14	Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
15	Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
16	Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
17	Preclinical Mouse Models To Study Human OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions in Vivo. Mol Pharm. 2015 Dec 7;12(12):4259-69.
18	Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
19	Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
20	Identification of drugs and drug metabolites as substrates of multidrug resistance protein 2 (MRP2) using triple-transfected MDCK-OATP1B1-UGT1A1-MRP2 cells. Br J Pharmacol. 2012 Mar;165(6):1836-1847.
21	The effect of SLCO1B115 on the disposition of pravastatin and pitavastatin is substrate dependent: the contribution of transporting activity changes by SLCO1B115. Pharmacogenet Genomics. 2008 May;18(5):424-33.
22	Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol. 2007 Dec;63(12):1161-9.
23	Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism. Clin Chim Acta. 2009 Jul;405(1-2):49-52.
24	FDA Drug Development and Drug Interactions
25	Interaction of methotrexate with organic-anion transporting polypeptide 1A2 and its genetic variants. J Pharmacol Exp Ther. 2006 Aug;318(2):521-9.
26	Localization of organic anion transporting polypeptide 4 (Oatp4) in rat liver and comparison of its substrate specificity with Oatp1, Oatp2 and Oatp3. Pflugers Arch. 2001 Nov;443(2):188-95.
27	Environmental and genetic factors affecting transport of imatinib by OATP1A2. Clin Pharmacol Ther. 2011 Jun;89(6):816-20.
28	Influence of the flavonoids apigenin, kaempferol, and quercetin on the function of organic anion transporting polypeptides 1A2 and 2B1. Biochem Pharmacol. 2010 Dec 1;80(11):1746-53.
29	Transporter-mediated influx and efflux mechanisms of pitavastatin, a new inhibitor of HMG-CoA reductase. J Pharm Pharmacol. 2005 Oct;57(10):1305-11.
30	Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology. 2006 May;130(6):1793-806.
31	Human organic anion-transporting polypeptide OATP-A (SLC21A3) acts in concert with P-glycoprotein and multidrug resistance protein 2 in the vectorial transport of Saquinavir in Hep G2 cells. Mol Pharm. 2004 Jan 12;1(1):49-56.
32	Uptake of enalapril and expression of organic anion transporting polypeptide 1 in zonal, isolated rat hepatocytes. Drug Metab Dispos. 2000 Jul;28(7):801-6.
33	Molecular and functional characterization of an organic anion transporting polypeptide cloned from human liver. Gastroenterology. 1995 Oct;109(4):1274-82.
34	Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner. Endocrinology. 2001 May;142(5):2005-12.
35	LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology. 2001 Jun;120(7):1689-99.
36	Effect of pregnane X receptor ligands on transport mediated by human OATP1B1 and OATP1B3. Eur J Pharmacol. 2008 Apr 14;584(1):57-65.
37	Influence of non-steroidal anti-inflammatory drugs on organic anion transporting polypeptide (OATP) 1B1- and OATP1B3-mediated drug transport. Drug Metab Dispos. 2011 Jun;39(6):1047-53.
38	Relevance of conserved lysine and arginine residues in transmembrane helices for the transport activity of organic anion transporting polypeptide 1B3. Br J Pharmacol. 2010 Feb 1;159(3):698-708.
39	Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009 Oct;158(3):693-705.
40	Cellular pharmacology of gemcitabine. Ann Oncol. 2006 May;17 Suppl 5:v7-12.
41	PAN-811 inhibits oxidative stress-induced cell death of human Alzheimer's disease-derived and age-matched olfactory neuroepithelial cells via suppression of intracellular reactive oxygen species. J Alzheimers Dis. 2009;17(3):611-9.
42	Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
43	Phase I study of oral gemcitabine prodrug (LY2334737) in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2013 Jun;71(6):1645-55.
44	Gallium maltolate is a promising chemotherapeutic agent for the treatment of hepatocellular carcinoma. Anticancer Res. 2006 May-Jun;26(3A):1739-43.
45	Tezacitabine Hoechst Marion Roussel.Curr Opin Investig Drugs.2000 Sep;1(1):135-40.
46	Phase I and pharmacokinetic study of the oral tris-(8-quinolinolato)gallium(III) complex (FFC11, KP46) in patients with solid tumors - a study of the CESAR Central European Society for Anticancer Drug Research - EWIV. J Clin Oncol (Meeting Abstracts) June 2005 vol. 23 no. 16_suppl 3205.
47	Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
48	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
49	Johnson EJ, MacGowan AP, Potter MN, et al "Reduced absorption of oral ciprofloxacin after chemotherapy for haematological malignancy." J Antimicrob Chemother 25 (1990): 837-42. [PMID: 2373666]
50	Cerner Multum, Inc. "Australian Product Information.".
51	Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
52	Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
53	Bennett CL, Nebeker JR, Samore MH, et al "The Research on Adverse Drug Events and Reports (RADAR) project." JAMA 293 (2005): 2131-40. [PMID: 15870417]
54	Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
55	Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
56	Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
57	Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
58	CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]