Details of the Drug

General Information of Drug (ID: DMY2KX9)

Drug Name

Alendronate

Synonyms

Arendal; Fosamax; ALENDRONATE SODIUM; ALENDRONIC ACID; Acide alendronique; Acido alendronico; Acidum alendronicum; MK 217; Acide alendronique [INN-French]; Acido alendronico [INN-Spanish]; Acidum alendronicum [INN-Latin]; Alendronic acid (INN); Alendronic acid [INN:BAN]; Bisphosphonate, 65; Fosamax (TN); MK-217; Phosphonic acid, (4-amino-1-hydroxybutylidene)bis; (4-Amino-1-hydroxybutylidene)bisphosphonic acid; (4-Amino-1-hydroxybutylidene)diphosphonic acid; (4-amino-1-hydroxy-1-phosphonobutyl)phosphonic acid; (4-amino-1-hydroxybutane-1,1-diyl)bis(phosphonic acid); 4-Amino-1-hydroxybutane-1,1-diphosphonate; 4-Amino-1-hydroxybutane-1,1-diphosphonic Acid; 4-Amino-1-hydroxybutylidene-1,1-bis(phosphonic acid); 4-Amino-1-hydroxybutylidene-1,1-bisphosphonate

Indication

Disease Entry	ICD 11	Status	REF
Osteoporosis	FB83.0	Approved	[1], [2]
Paget's disease	FB85	Approved	[1], [2]

Therapeutic Class

Bone Density Conservation Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 2

Molecular Weight (mw)

249.1

Topological Polar Surface Area (xlogp)

-6.5

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption Tmax: The time to maximum plasma concentration (Tmax) is 4-5 h [3]
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [4]
Clearance: The clearance of drug is 71 mL/min [5]
Elimination: Administration of radiolabeled alendronic acid results in 50% recovery in urine within 72 hours [6]
Half-life: The concentration or amount of drug in body reduced by one-half in 10 years [3]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 2.67766 micromolar/kg/day [7]
Unbound Fraction: The unbound fraction of drug in plasma is 0.22% [8]
Vd: The volume of distribution (Vd) of drug is 28 L [5]

Chemical Identifiers

Formula: C4H13NO7P2
IUPAC Name: (4-amino-1-hydroxy-1-phosphonobutyl)phosphonic acid
Canonical SMILES: C(CC(O)(P(=O)(O)O)P(=O)(O)O)CN
InChI: InChI=1S/C4H13NO7P2/c5-3-1-2-4(6,13(7,8)9)14(10,11)12/h6H,1-3,5H2,(H2,7,8,9)(H2,10,11,12)
InChIKey: OGSPWJRAVKPPFI-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 2088
ChEBI ID: CHEBI:2567
CAS Number: 66376-36-1
DrugBank ID: DB00630
TTD ID: D09KLR
ACDINA ID: D00017

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Geranyltranstransferase (FDPS)	TTIKWV4	FPPS_HUMAN	Modulator	[9]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

ICD Disease Classification

15 Disease of the musculoskeletal system/connective tissue

Disease Class

ICD-11: FA20 Rheumatoid arthritis

The Studied Tissue

Bone marrow

The Studied Disease

Osteoporosis [ICD-11:FA20]

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Geranyltranstransferase (FDPS)	DTT	FDPS	7.06E-03	-0.73	-2.57

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Magnesium Sulfate	DMVEK07	Moderate	Decreased absorption of Alendronate due to formation of complexes caused by Magnesium Sulfate.	Acute pain [MG31]	[17]
Framycetin	DMF8DNE	Moderate	Increased risk of hypocalcemia by the combination of Alendronate and Framycetin.	Alcoholic liver disease [DB94]	[18]
Kanamycin	DM2DMPO	Moderate	Increased risk of hypocalcemia by the combination of Alendronate and Kanamycin.	Bacterial infection [1A00-1C4Z]	[18]
Streptomycin	DME1LQN	Moderate	Increased risk of hypocalcemia by the combination of Alendronate and Streptomycin.	Bacterial infection [1A00-1C4Z]	[18]
Gentamicin	DMKINJO	Moderate	Increased risk of hypocalcemia by the combination of Alendronate and Gentamicin.	Bacterial infection [1A00-1C4Z]	[18]
Netilmicin	DMRD1QK	Moderate	Increased risk of hypocalcemia by the combination of Alendronate and Netilmicin.	Bacterial infection [1A00-1C4Z]	[18]
Tobramycin	DMUI0CH	Moderate	Increased risk of hypocalcemia by the combination of Alendronate and Tobramycin.	Bacterial infection [1A00-1C4Z]	[18]
Phenylbutazone	DMAYL0T	Moderate	Increased risk of nephrotoxicity by the combination of Alendronate and Phenylbutazone.	Chronic pain [MG30]	[19]
Ketoprofen	DMRKXPT	Moderate	Increased risk of nephrotoxicity by the combination of Alendronate and Ketoprofen.	Chronic pain [MG30]	[19]
Ethacrynic acid	DM60QMR	Moderate	Increased risk of hypocalcemia by the combination of Alendronate and Ethacrynic acid.	Essential hypertension [BA00]	[20]
Mefenamic acid	DMK7HFI	Moderate	Increased risk of nephrotoxicity by the combination of Alendronate and Mefenamic acid.	Female pelvic pain [GA34]	[19]
Furosemide	DMMQ8ZG	Moderate	Increased risk of hypocalcemia by the combination of Alendronate and Furosemide.	Heart failure [BD10-BD1Z]	[20]
Bumetanide	DMRV7H0	Moderate	Increased risk of hypocalcemia by the combination of Alendronate and Bumetanide.	Heart failure [BD10-BD1Z]	[20]
Didanosine	DMI2QPE	Moderate	Decreased absorption of Alendronate due to formation of complexes caused by Didanosine.	Human immunodeficiency virus disease [1C60-1C62]	[17]
Etelcalcetide	DMHP9BL	Major	Increased risk of hypocalcemia by the combination of Alendronate and Etelcalcetide.	Hyper-parathyroidism [5A51]	[21]
Quinapril	DMR8H31	Moderate	Decreased absorption of Alendronate due to formation of complexes caused by Quinapril.	Hypertension [BA00-BA04]	[21]
Meclofenamic acid	DM05FXR	Moderate	Increased risk of nephrotoxicity by the combination of Alendronate and Meclofenamic acid.	Inflammatory spondyloarthritis [FA92]	[19]
Iron	DMAP8MV	Moderate	Decreased absorption of Alendronate due to formation of complexes caused by Iron.	Iron deficiency anaemia [3A00]	[17]
Exjade	DMHPRWG	Major	Increased risk of nephrotoxicity by the combination of Alendronate and Exjade.	Mineral absorption/transport disorder [5C64]	[22]
Lanthanum carbonate	DMMJQSH	Moderate	Decreased absorption of Alendronate due to formation of complexes caused by Lanthanum carbonate.	Mineral absorption/transport disorder [5C64]	[23]
Naproxen	DMZ5RGV	Moderate	Increased risk of nephrotoxicity by the combination of Alendronate and Naproxen.	Osteoarthritis [FA00-FA05]	[19]
Aspirin	DM672AH	Moderate	Increased risk of nephrotoxicity by the combination of Alendronate and Aspirin.	Pain [MG30-MG3Z]	[19]
Etodolac	DM6WJO9	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Alendronate and Etodolac.	Pain [MG30-MG3Z]	[19]
Diflunisal	DM7EN8I	Moderate	Increased risk of nephrotoxicity by the combination of Alendronate and Diflunisal.	Pain [MG30-MG3Z]	[19]
Ibuprofen	DM8VCBE	Moderate	Increased risk of nephrotoxicity by the combination of Alendronate and Ibuprofen.	Pain [MG30-MG3Z]	[19]
Choline salicylate	DM8P137	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Alendronate and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[19]
Bromfenac	DMKB79O	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Alendronate and Bromfenac.	Postoperative inflammation [1A00-CA43]	[19]
Salsalate	DM13P4C	Moderate	Increased risk of nephrotoxicity by the combination of Alendronate and Salsalate.	Rheumatoid arthritis [FA20]	[19]
Meloxicam	DM2AR7L	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Alendronate and Meloxicam.	Rheumatoid arthritis [FA20]	[19]
Oxaprozin	DM9UB0P	Moderate	Increased risk of nephrotoxicity by the combination of Alendronate and Oxaprozin.	Rheumatoid arthritis [FA20]	[19]
Flurbiprofen	DMGN4BY	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Alendronate and Flurbiprofen.	Rheumatoid arthritis [FA20]	[19]
Salicyclic acid	DM2F8XZ	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Alendronate and Salicyclic acid.	Seborrhoeic dermatitis [EA81]	[19]
Plazomicin	DMKMBES	Moderate	Increased risk of hypocalcemia by the combination of Alendronate and Plazomicin.	Urinary tract infection [GC08]	[18]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Acesulfame	E00341	36573	Flavoring agent
Kyselina citronova	E00014	311	Acidulant; Antioxidant; Buffering agent; Complexing agent; Flavoring agent
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
Sucralose	E00370	71485	Flavoring agent
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Carbonic acid disodium salt	E00199	10340	Alkalizing agent; Buffering agent; Diluent; Dispersing agent
Carmellose sodium	E00625	Not Available	Disintegrant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Monosodium citrate	E00550	23666341	Acidulant; Antimicrobial preservative; Buffering agent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Sodium bicarbonate	E00424	516892	Alkalizing agent; Diluent
Vinylpyrrolidone	E00668	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Alendronic acid 70 mg tablet	70 mg	Effervescent Oral Tablet	Oral
Alendronic acid 40 mg tablet	40 mg	Oral Tablet	Oral
Alendronic acid 10 mg tablet	10 mg	Oral Tablet	Oral
Alendronic acid 35 mg tablet	35 mg	Oral Tablet	Oral
Alendronic acid 5 mg tablet	5 mg	Oral Tablet	Oral
Alendronic acid 70 mg tablet	70 mg	Oral Tablet	Oral

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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: 3141).
2	Osteonecrosis of the jaw. South Med J. 2008 Feb;101(2):160-5.
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4	BDDCS applied to over 900 drugs
5	An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
6	Lin JH, Chen IW, deLuna FA, Hichens M: Role of calcium in plasma protein binding and renal handling of alendronate in hypo- and hypercalcemic rats. J Pharmacol Exp Ther. 1993 Nov;267(2):670-5.
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	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
9	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
10	Synthesis, chiral high performance liquid chromatographic resolution and enantiospecific activity of a potent new geranylgeranyl transferase inhibitor, 2-hydroxy-3-imidazo[1,2-a]pyridin-3-yl-2-phosphonopropionic acid. J Med Chem. 2010 May 13;53(9):3454-64.
11	Detection of nonsterol isoprenoids by HPLC-MS/MS. Anal Biochem. 2008 Dec 1;383(1):18-24.
12	Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther. 2001 Feb;296(2):235-42.
13	Activity of bisphosphonates against Trypanosoma brucei rhodesiense. J Med Chem. 2002 Jul 4;45(14):2904-14.
14	Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: time-dependent inhibition of hu... J Med Chem. 2008 Apr 10;51(7):2187-95.
15	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
16	The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
17	Product Information. Bonefos (clodronate). Rhone-Poulenc Rorer Canada Inc, Laval, QC.
18	Chang JT, Green L, Beitz J "Renal failure with the use of zoledronic acid." N Engl J Med 349 (2003): 1676-9 discussion 1676-9. [PMID: 14573746]
19	Product Information. Actonel (risedronate). Procter and Gamble Pharmaceuticals, Cincinnati, OH.
20	Product Information. Skelid (tilundronate). Sanofi Winthrop Pharmaceuticals, New York, NY.
21	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
22	Product Information. Exjade (deferasirox). Novartis Pharmaceuticals, East Hanover, NJ.
23	Canadian Pharmacists Association.