Details of the Drug

General Information of Drug (ID: DMU8JGH)

Drug Name

Hydralazine

Synonyms

Apresolin; Apresoline; Apressin; Apressoline; Aprezolin; HLZ; Hidral; Hidralazin; Hidralazina; Hipoftalin; Hydralazin; Hydralazinum; Hydrallazin; Hydrallazine; Hydrazinophthalazine; Hypophthalin; Idralazina; Hidralazina [Spanish]; Idralazina [DCIT]; Idralazina [Italian]; BA 5968; C 5968; Ciba 5968; Praparat 5968; Apresoline (TN); Apressin (pharmaceutical); C-5068; C-5968; Hidral (TN); Hidralazina [INN-Spanish]; Hydralazine (INN); Hydralazine [INN:BAN]; Hydralazinum [INN-Latin]; Hydrazone 1(2H)-phthalazinone; Phthalazin-1-ylhydrazine; [2H-Phthalazin-(1Z)-Ylidene]-Hydrazine Hydrochloride; (1Z)-1(2H)-Phthalazinone hydrazone; (2H)-Phthalazinone hydrazone; 1(2H)-Phthalazinone hydrazone; 1(2H)-Phthalazinone, hydrazone; 1-Hydrazinophthalazine; 1-Phthalazinylhydrazine; 6-Hydralazine

Indication

Disease Entry	ICD 11	Status	REF
Chronic heart failure	BD1Z	Approved	[1]
Hypertension	BA00-BA04	Approved	[2]
Malignant essential hypertension	BA00	Approved	[1]
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Therapeutic Class

Antihypertensive Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

160.18

Logarithm of the Partition Coefficient (xlogp)

0.7

Rotatable Bond Count (rotbonds)

1

Hydrogen Bond Donor Count (hbonddonor)

2

Hydrogen Bond Acceptor Count (hbondacc)

4

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
Clearance: The clearance of drug is 1.77 +/- 0.48 L/h/kg [4]
Elimination: Less than 10% of drug is recovered in the feces and 65-90% is recovered in the urine [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 57 - 241 minutes (in heart failure patients), and 200 minutes (in hypertensive patients) [4]
Metabolism: The drug is metabolized via the glucuronidation [5]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 20.78914 micromolar/kg/day [6]
Unbound Fraction: The unbound fraction of drug in plasma is 0.12% [7]
Vd: The volume of distribution (Vd) of drug is 1.34 +/- 0.79 L/kg [4]
Water Solubility: The ability of drug to dissolve in water is measured as 44.2 mg/mL [3]

Chemical Identifiers

Formula: C8H8N4
IUPAC Name: phthalazin-1-ylhydrazine
Canonical SMILES: C1=CC=C2C(=C1)C=NN=C2NN
InChI: InChI=1S/C8H8N4/c9-11-8-7-4-2-1-3-6(7)5-10-12-8/h1-5H,9H2,(H,11,12)
InChIKey: RPTUSVTUFVMDQK-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 3637
ChEBI ID: CHEBI:5775
CAS Number: 86-54-4
DrugBank ID: DB01275
TTD ID: D0K1XK
VARIDT ID: DR00942
INTEDE ID: DR0813
ACDINA ID: D00311

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Membrane copper amine oxidase (AOC3)	TT7HC21	AOC3_HUMAN	Modulator	[8]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
N-acetyltransferase 1 (NAT1)	DE7OAB3	ARY1_HUMAN	Substrate	[9]
RNA cytidine acetyltransferase (hALP)	DEZV4AP	NAT10_HUMAN	Substrate	[10]
N-acetyltransferase 2 (NAT2)	DER7TA0	ARY2_HUMAN	Substrate	[9]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Adenomatous polyposis coli protein (APC)	OTKV0TIK	APC_HUMAN	Post-Translational Modifications	[11]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Protein Interaction/Cellular Processes	[12]
Arylamine N-acetyltransferase 2 (NAT2)	OTBPDQOY	ARY2_HUMAN	Biotransformations	[13]
Bis(5'-adenosyl)-triphosphatase (FHIT)	OTGWBSLA	FHIT_HUMAN	Gene/Protein Processing	[11]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Gene/Protein Processing	[14]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Gene/Protein Processing	[15]
Cyclin-dependent kinase inhibitor 2A (CDKN2A)	OTN0ZWAE	CDN2A_HUMAN	Post-Translational Modifications	[11]
Death-associated protein kinase 1 (DAPK1)	OTNCNUCO	DAPK1_HUMAN	Gene/Protein Processing	[11]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Gene/Protein Processing	[11]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Gene/Protein Processing	[11]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Chronic heart failure

ICD Disease Classification

BD1Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Membrane copper amine oxidase (AOC3)	DTT	AOC3	8.36E-22	-1.03	-1.54
RNA cytidine acetyltransferase (hALP)	DME	NAT10	1.53E-02	1.17E-01	4.09E-01
N-acetyltransferase 2 (NAT2)	DME	NAT2	7.77E-14	-2.86E-01	-6.87E-01
N-acetyltransferase 1 (NAT1)	DME	NAT1	1.17E-06	2.81E-01	4.42E-01

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Hydralazine

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Penbutolol	DM4ES8F	Minor	Decreased metabolism of Hydralazine caused by Penbutolol mediated interference with first-pass metabolism.	Hypertension [BA00-BA04]	[16]
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Coadministration of a Drug Treating the Disease Different from Hydralazine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Cariprazine	DMJYDVK	Moderate	Additive hypotensive effects by the combination of Hydralazine and Cariprazine.	Bipolar disorder [6A60]	[17]
OPC-34712	DMHG57U	Moderate	Additive hypotensive effects by the combination of Hydralazine and OPC-34712.	Depression [6A70-6A7Z]	[17]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of peripheral neuropathy by the combination of Hydralazine and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[18]
ITI-007	DMUQ1DO	Moderate	Additive hypotensive effects by the combination of Hydralazine and ITI-007.	Insomnia [7A00-7A0Z]	[17]
Ozanimod	DMT6AM2	Moderate	Additive hypotensive effects by the combination of Hydralazine and Ozanimod.	Multiple sclerosis [8A40]	[19]
Rasagiline	DM3WKQ4	Moderate	Additive hypotensive effects by the combination of Hydralazine and Rasagiline.	Parkinsonism [8A00]	[19]
Levomepromazine	DMIKFEL	Moderate	Additive hypotensive effects by the combination of Hydralazine and Levomepromazine.	Psychotic disorder [6A20-6A25]	[17]
Iloperidone	DM6AUFY	Moderate	Additive hypotensive effects by the combination of Hydralazine and Iloperidone.	Schizophrenia [6A20]	[17]
Molindone	DMAH70G	Moderate	Additive hypotensive effects by the combination of Hydralazine and Molindone.	Schizophrenia [6A20]	[17]
Thiothixene	DMDINC4	Moderate	Additive hypotensive effects by the combination of Hydralazine and Thiothixene.	Schizophrenia [6A20]	[17]
Asenapine	DMSQZE2	Moderate	Additive hypotensive effects by the combination of Hydralazine and Asenapine.	Schizophrenia [6A20]	[17]
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⏷ Show the Full List of 11 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
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Stearic acid	E00079	5281	Emulsifying agent; Solubilizing agent; Viscosity-controlling agent; lubricant
Sunset yellow FCF	E00255	17730	Colorant
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Sodium stearoyl lactylate	E00558	23671849	Emulsifying agent
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Vinylpyrrolidone	E00668	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
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⏷ Show the Full List of 11 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Hydralazine 10 mg tablet	10 mg	Oral Tablet	Oral
Hydralazine 100 mg tablet	100 mg	Oral Tablet	Oral
Hydralazine 25 mg tablet	25 mg	Oral Tablet	Oral
Hydralazine 50 mg tablet	50 mg	Oral Tablet	Oral

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References

1	Hydralazine FDA Label
2	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: 7326).
3	BDDCS applied to over 900 drugs
4	Clinical pharmacokinetics and therapeutic use of hydralazine in congestive heart failure. Clin Pharmacokinet. 1989 Feb;16(2):86-9. doi: 10.2165/00003088-198916020-00003.
5	Dubinsky MC: Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety. Clin Gastroenterol Hepatol. 2004 Sep;2(9):731-43.
6	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
7	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
8	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
9	N-acetyltransferase 2 genotype-dependent N-acetylation of hydralazine in human hepatocytes. Drug Metab Dispos. 2017 Dec;45(12):1276-1281.
10	Prizidilol, an antihypertensive with precapillary vasodilator and beta-adrenoceptor blocking actions, in primary hypertension. Clin Pharmacol Ther. 1981 May;29(5):588-93.
11	A phase I study of hydralazine to demethylate and reactivate the expression of tumor suppressor genes. BMC Cancer. 2005 Apr 29;5:44.
12	Albumin Protects Lung Cells against Acrolein Cytotoxicity and Acrolein-Adducted Albumin Increases Heme Oxygenase 1 Transcripts. Chem Res Toxicol. 2020 Jul 20;33(7):1969-1979. doi: 10.1021/acs.chemrestox.0c00146. Epub 2020 Jun 29.
13	Eukaryotic arylamine N-acetyltransferase. Investigation of substrate specificity by high-throughput screening. Biochem Pharmacol. 2005 Jan 15;69(2):347-59. doi: 10.1016/j.bcp.2004.09.014. Epub 2004 Nov 24.
14	High-throughput measurement of the Tp53 response to anticancer drugs and random compounds using a stably integrated Tp53-responsive luciferase reporter. Carcinogenesis. 2002 Jun;23(6):949-57. doi: 10.1093/carcin/23.6.949.
15	Hydralazine inhibits human peritoneal mesothelial cell proliferation and collagen synthesis. Nephrol Dial Transplant. 1996 Nov;11(11):2276-81. doi: 10.1093/oxfordjournals.ndt.a027148.
16	Amemiya M, Tabei K, Furuya H, Sakairi Y, Asano Y "Pharmacokinetics of carteolol in patients with impaired renal function." Eur J Clin Pharmacol 43 (1992): 417-21. [PMID: 1451723]
17	Aronowitz JS, Chakos MH, Safferman AZ, Lieberman JA "Syncope associated with the combination of clozapine and enalapril." J Clin Psychopharmacol 14 (1994): 429-30. [PMID: 7884028]
18	Carrion C, Espinosa E, Herrero A, Garcia B "Possible vincristine-isoniazid interaction." Ann Pharmacother 29 (1995): 201. [PMID: 7756727]
19	Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6. [PMID: 1116424]