ALENDRONIC ACID

Details

Stereochemistry	ACHIRAL
Molecular Formula	C4H13NO7P2
Molecular Weight	249.0962
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C(CC(O)(P(=O)(O)O)P(=O)(O)O)CN

InChI

InChIKey=OGSPWJRAVKPPFI-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020560s069,021575s025lbl.pdf

Alendronic acid is a bisphosphonate drug used for osteoporosis, osteogenesis imperfecta, and several other bone diseases. It is marketed alone as well as in combination with vitamin D. Alendronate inhibits osteoclast-mediated bone-resorption. Like all bisphosphonates, it is chemically related to inorganic pyrophosphate, the endogenous regulator of bone turnover. But while pyrophosphate inhibits both osteoclastic bone resorption and the mineralization of the bone newly formed by osteoblasts, alendronate specifically inhibits bone resorption without any effect on mineralization at pharmacologically achievable doses. Its inhibition of bone-resorption is dose-dependent and approximately 1,000 times stronger than the equimolar effect of the first bisphosphonate drug, etidronate. Under therapy, normal bone tissue develops, and alendronate is deposited in the bone-matrix in a pharmacologically inactive form. For optimal action, enough calcium and vitamin D are needed in the body in order to promote normal bone development. Hypocalcemia should, therefore, be corrected before starting therapy. Treatment of post-menopausal women and people with osteogenesis imperfecta over the age of 22 with alendronic acid has demonstrated normalization of the rate of bone turnover, significant increase in BMD (bone mineral density) of the spine, hip, wrist and total body, and significant reductions in the risk of vertebral (spine) fractures, wrist fractures, hip fractures, and all non-vertebral fractures. In the Fracture Intervention Trial, the women with the highest risk of fracture (by virtue of pre-existing vertebral fractures) were treated with Fosamax 5 mg/day for two years followed by 10 mg/day for the third year. This resulted in approximately 50% reductions in fractures of the spine, hip, and wrist compared with the control group taking placebos. Both groups also took calcium and vitamin D.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Farnesyl diphosphate synthase 28 Target ID: CHEMBL1782 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18327899	Inhibitor 7701		260.0 nM [IC50]
Geranylgeranyl pyrophosphate synthetase 18 Target ID: CHEMBL4769 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18800762	Inhibitor 7701		436.52 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Osteoporosis 96 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020560s069,021575s025lbl.pdf	Primary	Approved 7997	FOSAMAX Approved Use INDICATIONS AND USAGE. FOSAMAX is a bisphosphonate indicated for: Treatment and prevention of osteoporosis in postmenopausal women (1.1, 1.2) Treatment to increase bone mass in men with osteoporosis (1.3) Treatment of glucocorticoid-induced osteoporosis (1.4) Treatment of Paget's disease of bone (1.5) Important limitations of use: The optimal duration of use has not been determined. The need for continued therapy should be re-evaluated on a periodic basis. (1.6) Launch Date 9.3381119E11
Glucocorticoid-induced osteoporosis 11 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020560s069,021575s025lbl.pdf	Primary	Approved 7997	FOSAMAX Approved Use INDICATIONS AND USAGE. FOSAMAX is a bisphosphonate indicated for: Treatment and prevention of osteoporosis in postmenopausal women (1.1, 1.2) Treatment to increase bone mass in men with osteoporosis (1.3) Treatment of glucocorticoid-induced osteoporosis (1.4) Treatment of Paget's disease of bone (1.5) Important limitations of use: The optimal duration of use has not been determined. The need for continued therapy should be re-evaluated on a periodic basis. (1.6) Launch Date 9.3381119E11
Paget's disease 16 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020560s069,021575s025lbl.pdf	Primary	Approved 7997	FOSAMAX Approved Use INDICATIONS AND USAGE. FOSAMAX is a bisphosphonate indicated for: Treatment and prevention of osteoporosis in postmenopausal women (1.1, 1.2) Treatment to increase bone mass in men with osteoporosis (1.3) Treatment of glucocorticoid-induced osteoporosis (1.4) Treatment of Paget's disease of bone (1.5) Important limitations of use: The optimal duration of use has not been determined. The need for continued therapy should be re-evaluated on a periodic basis. (1.6) Launch Date 9.3381119E11

C_max

Value	Dose	Co-administered	Analyte	Population
56.62 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28744102	70 mg single, oral dose: 70 mg route of administration: Oral experiment type: SINGLE co-administered:		ALENDRONATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
155.53 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28744102	70 mg single, oral dose: 70 mg route of administration: Oral experiment type: SINGLE co-administered:		ALENDRONATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.73 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28744102	70 mg single, oral dose: 70 mg route of administration: Oral experiment type: SINGLE co-administered:		ALENDRONATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:2567	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2567
ChemicalBook	CB3380835	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3380835
ZINC	ZINC000003801919	http://zinc15.docking.org/substances/ZINC000003801919
eMolecules	901346	https://www.emolecules.com/cgi-bin/more?vid=901346

PubMed

Title	Date	PubMed
Long-term therapy for postmenopausal osteoporosis: stronger bones but weaker arteries.	1999 Jul 27	10447376
Ocular inflammation associated with alendronate therapy.	1999 Jun	10369603
[Pain relief with alendronate therapy in a breast cancer patient with bone metastasis].	2000 Apr	10791010
Apoptosis of osteoclast-like cells induced by alendronate is related to Fas gene expression.	2000 Aug	11314515
Alendronate is a specific, nanomolar inhibitor of farnesyl diphosphate synthase.	2000 Jan 1	10620343
A peptide prodrug approach for improving bisphosphonate oral absorption.	2000 Oct 5	11020278
Initiation of osteoporosis treatment after bone mineral density testing.	2001	11444079
Alendronate: an update of its use in osteoporosis.	2001	11434454
A slow outward current and a hypoosmolality induced anion conductance in embryonic chicken osteoclasts.	2001	11396841
Hyposecretion of the adrenal androgen dehydroepiandrosterone sulfate and its relation to clinical variables in inflammatory arthritis.	2001	11299059
Fractures after long-term alendronate therapy.	2001 Apr	11297626
Risk of ulcer soars with combination of arthritis drugs.	2001 Apr	11290669
Analgesic effect of bisphosphonates in mice.	2001 Apr	11275384
Effect of alendronate on bone mineral density in male idiopathic osteoporosis.	2001 Aug	11474478
Clinical and radiological improvement of periodontal disease in patients with type 2 diabetes mellitus treated with alendronate: a randomized, placebo-controlled trial.	2001 Feb	11288794
Alendronate in rheumatoid arthritis patients treated with methotrexate and glucocorticoids.	2001 Feb	11269535
Osteoporosis therapies for rheumatoid arthritis patients: minimizing gastrointestinal side effects.	2001 Feb	11182029
[Diagnosis of primary Sjogren's syndrome].	2001 Feb 20	11301610
Prevention of bone loss in kidney graft recipients.	2001 Feb-Mar	11267228
Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo-controlled extension trial.	2001 Jan	11212161
Once-a-week alendronate for postmenopausal osteoporosis is as effective as once-daily dosing.	2001 Jan	11196334
Phosphate ions mediate chondrocyte apoptosis through a plasma membrane transporter mechanism.	2001 Jan	11165936
[Bisphosphonate treatment prevents hip fractures in 70-79 year old women with osteoporotic vertebral fractures].	2001 Jul 14	11484428
New possibilities for diagnosis and treatment of osteoporosis.	2001 Jul-Aug	11563832
Prevalence and determinants of osteoporosis drug prescription among patients with high exposure to glucocorticoid drugs.	2001 Jun	11439733
Osteoporosis.	2001 Jun	11402788
Osteoporosis in men.	2001 Jun 15	11430449
Estimating probability of non-response to treatment using mixture distributions.	2001 Jun 30	11406838
Excretion of sweat and urine pyridinoline crosslinks in healthy controls and subjects with established metabolic bone disease.	2001 Mar	11350019
Prevention of corticosteroid induced osteoporosis in inpatients recently discharged from a tertiary teaching hospital.	2001 Mar	11296960
Evidence-based medicine: putting theory into practice.	2001 Mar	11291467
Managing menopause after breast cancer: balancing risks and benefits.	2001 Mar	11263852
Osteoporosis. Efficacy and safety of a bisphosphonate dosed once weekly.	2001 Mar	11252758
Effect of alendronate and MK-677 (a growth hormone secretagogue), individually and in combination, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women.	2001 Mar	11238495
Labelling of Re-ABP with 188Re for bone pain palliation.	2001 Mar	11214878
Once-a-week alendronate (Fosamax).	2001 Mar 19	11257718
[Esophagitis associated with use of alendronate in 5 postmenopausic patients].	2001 May	11471319
Why do older women discontinue hormone replacement therapy?	2001 May	11445025
Bones and Crohn's: should we treat Crohn's disease patients with alendronate?	2001 May	11383592
Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles.	2001 May	11344052
Absolute vs. relative numbers in evaluating drug therapy.	2001 May 15	11388707
Prevention of bone loss and fracture after lung transplantation: a pilot study.	2001 Oct 15	11602851
Comparison of calcitonin, alendronate and fluorophosphate effects on ovariectomized rat bone.	2001 Sep	11669503
Bisphosphonate therapy for Paget's disease in a patient with hypoparathyroidism: profound hypocalcemia, rapid response, and prolonged remission.	2001 Sep	11547843
Regression to the mean: what does it mean? Using bone density results to monitor treatment of osteoporosis.	2001 Spring	11309514
What is the impact of osteoporosis education and bone mineral density testing for postmenopausal women in a managed care setting?	2001 Summer	11256875

Patents

Sample Use Guides

In Vivo Use Guide

Treatment of Osteoporosis in Postmenopausal Women: one 70 mg tablet once weekly Prevention of Osteoporosis in Postmenopausal Women: one 35 mg tablet once weekly Treatment to Increase Bone Mass in Men with Osteoporosis: one 70 mg tablet once weekly

Route of Administration: Oral

In Vitro Use Guide

IGROV-1 ovarian carcinoma cells were stained with PKH26 (Sigma-Aldrich) according to the manufacturer’s instructions and then incubated with the indicated AA (Alendronic acid ) for 24 h. After washing, 1 3 106 target cells and 1 3 106 ex vivo expanded gd T cells were cocultured at 37°C/5% CO2 for 4 h and then stained with Annexin VFITC (BD Pharmingen)

Name

Type

Language

ALENDRONIC ACID

Official Name

English

ALENDRONIC ACID [EMA EPAR]

Common Name

English

P,P'-(4-AMINO-1-HYDROXYBUTYLIDENE)BISPHOSPHONIC ACID

Systematic Name

English

.ALPHA.-HYDROXY-.DELTA.-AMINOBUTYLIDENEDIPHOSPHONIC ACID

Systematic Name

English

ABDP

Common Name

English

ALENDRONIC ACID [WHO-DD]

Common Name

English

ALENDRONATE [VANDF]

Common Name

English

(4-AMINO-1-HYDROXYBUTYLIDENE)DIPHOSPHONIC ACID

Systematic Name

English

PHOSPHONIC ACID, (4-AMINO-1-HYDROXYBUTYLIDENE)BIS-

Common Name

English

ALENDRONIC ACID [INN]

Common Name

English

PHOSPHONIC ACID, P,P'-(4-AMINO-1-HYDROXYBUTYLIDENE)BIS-

Common Name

English

4-AMINO-1-HYDROXYBUTANE-1,1-DIPHOSPHONIC ACID

Systematic Name

English

ALENDRONATE [MART.]

Common Name

English

(4-AMINO-1-HYDROXYBUTANE-1,1-DIYL)BIS(PHOSPHONIC ACID)

Systematic Name

English

ALENDRONIC ACID [MI]

Common Name

English

ALENDRONATE

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

166603