Ibandronic acid

Ibandronic acid is a bisphosphonate medication used in the prevention and treatment of osteoporosis and metastasis-associated skeletal fractures in people with cancer.^[4] It may also be used to treat hypercalcemia (elevated blood calcium levels). It is typically formulated as its sodium salt ibandronate sodium.^{[medical citation needed]}

Ibandronic acid

Clinical data
Trade names	Boniva, Bonviva, Bondronat, others
AHFS/Drugs.com	Monograph
License data	EU EMA: by INN US DailyMed: Ibandronate_sodium US FDA: Ibandronate_sodium
Pregnancy category	AU: B3
Routes of administration	By mouth, intravenous
ATC code	M05BA06 (WHO)
Legal status
Legal status	US: ℞-only EU: Rx-only[1][2][3] In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	0.6%
Protein binding	90.9 to 99.5% (concentration-dependent)
Metabolism	Nil
Elimination half-life	10 to 60 hours
Excretion	Kidney
Identifiers
IUPAC name Hydroxy-[1-hydroxy-3-[methyl(pentyl)amino]-1-phosphonopropyl]phosphinate
CAS Number	114084-78-5 Y
PubChem CID	60852
IUPHAR/BPS	3059
DrugBank	DB00710 N
ChemSpider	54839 Y
UNII	UMD7G2653W
KEGG	D08056 Y as salt: D04486 Y
ChEBI	CHEBI:93770
ChEMBL	ChEMBL997 Y
PDB ligand	BFQ (PDBe, RCSB PDB)
CompTox Dashboard (EPA)	DTXSID5048340
ECHA InfoCard	100.214.537
Chemical and physical data
Formula	C9H23NO7P2
Molar mass	319.231 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=P(O)(O)C(O)(CCN(CCCCC)C)P(=O)(O)O
InChI InChI=1S/C9H23NO7P2/c1-3-4-5-7-10(2)8-6-9(11,18(12,13)14)19(15,16)17/h11H,3-8H2,1-2H3,(H2,12,13,14)(H2,15,16,17) Y Key:MPBVHIBUJCELCL-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

It was patented in 1986 by Boehringer Mannheim and approved for medical use in 1996.^[5]

Medical uses

Ibandronate is indicated for the treatment and prevention of osteoporosis in post-menopausal women.^[6] In May 2003, the US Food and Drug Administration (FDA) approved ibandronate as a daily treatment for post-menopausal osteoporosis.^{[medical citation needed]} The basis for this approval was a three-year, randomized, double-blind, placebo-controlled trial women with post-menopausal osteoporosis.^{[medical citation needed]} Each participant also received daily oral doses of calcium and 400IUs [international units] of vitamin D.^{[medical citation needed]} At the study's conclusion, both doses significantly reduced the occurrence risk of new vertebral fractures by 50–52 percent when compared to the effects of the placebo drug.^{[medical citation needed]}

Ibandronate is efficacious for the prevention of metastasis-related bone fractures in multiple myeloma, breast cancer, and certain other cancers.^[7]

Adverse effects

In 2008, the US Food and Drug Administration (FDA) issued a communication warning of the possibility of severe and sometimes incapacitating bone, joint or muscle pain.^[8] A study conducted by the American Society of Bone and Mineral Research concluded that long-term use of bisphosphonates, including Boniva, may increase the risk of a rare but serious fracture of the femur.^[9] The drug also has been associated with osteonecrosis of the jaw, a relatively rare but serious condition.^[10]

Pharmacology

Mechanism of action

Nitrogen containing bisphosphonates, which include ibandronate, pamidronate and alendronate exert their effects on osteoclasts mainly by inhibiting the synthesis of isoprenoid lipids such as isopentenyl diphosphate (IPP), farnesyl diphosphate (FPP), and geranylgeranyl diphosphate (GGPP) via the mevalonate pathway. These isoprenoids are used in posttranslational modification (prenylation) of small GTPases such as Ras, Rho, and Rac. These prenylated GTPases are necessary for various cellular processes including osteoclast morphology, endosome trafficking, and apoptosis.^[11]

Relative potency^[12]

Bisphosphonate	Relative potency
Etidronate	1
Tiludronate	10
Pamidronate	100
Alendronate	100-500
Ibandronate	500-1000
Risedronate	1000
Zoledronate	5000

Society and culture

Brand names

Ibandronic acid is sold under the brand names Boniva, Bondronat, Bonviva, Bandrone, Ibandrix, Adronil, Bondrova, Bonprove, and Fosfonat.