Chemistry:Ibandronic acid

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Short description: Chemical compound

Ibandronic acid
Clinical data
Trade namesBoniva, Bonviva, Bondronat, others
AHFS/Drugs.comMonograph
License data
Pregnancy
category
  • AU: B3
Routes of
administration		By mouth, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability0.6%
Protein binding90.9 to 99.5%
(concentration-dependent)
MetabolismNil
Elimination half-life10 to 60 hours
ExcretionKidney
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
Chemical and physical data
FormulaC9H23NO7P2
Molar mass319.231 g·mol−1
3D model (JSmol)
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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.[5]

Ibandronate, or ibandronic acid, is primarily used to prevent and treat postmenopausal osteoporosis in women.[6] Its U.S. brand name is Boniva,[6] and in contrast to most other bisphosphonate drugs, Ibandronate can be administered both orally and intravenously.[7]

It was patented in 1986 by Boehringer Mannheim and approved for medical use in 1996.[8]

Medical uses

Ibandronate is indicated for the treatment and prevention of osteoporosis in post-menopausal women.[9] In May 2003, the US Food and Drug Administration (FDA) approved ibandronate as a daily treatment for post-menopausal osteoporosis. The basis for this approval was a three-year, randomized, double-blind, placebo-controlled trial women with post-menopausal osteoporosis. Each participant also received daily oral doses of calcium and 400IUs [international units] of vitamin D. 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.

Ibandronate is efficacious for the prevention of metastasis-related bone fractures in multiple myeloma, breast cancer, and certain other cancers.[10]

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.[11] 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.[12] The drug also has been associated with osteonecrosis of the jaw, a relatively rare but serious condition.[13]

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.[14]

Relative potency[15]
Bisphosphonate Relative potency
Etidronate 1
Tiludronate 10
Pamidronate 100
Alendronate 100-500
Ibandronate 500-1000
Risedronate 1000
Zoledronate 5000

Absorption

Ibandronate has good oral absorption, for it only takes less than an hour for the drug to reach its peak concentration within the bloodstream.[7] The absorption of the oral tablet can be evaluated by analyzing the following factors of the chemical structure of the active drug Ibandronate: its molecular weight, hydrogen bond acceptors, hydrogen bond donors, and its clogP value. Generally, a medication is predicted to have good oral absorption if the chemical structure of the active ingredient has a molecular weight less than 500g/mol, has less than or equal to ten hydrogen bond acceptors, has less than or equal to five hydrogen bond donors, and its clogP value is less than or equal to five.[16] Ibandronate meets these criteria – its molecular weight is 319.23 g/mol, it has eight hydrogen bond acceptors, five hydrogen bond donors, and its clogP value is in the negative range.[16] It is important, however, to not confuse good oral absorption with bioavailability. Despite the drug’s rapid absorption, Ibandronate has a low bioavailability of 0.63%.[7]

Society and culture

Brand names

Ibandronic acid is sold under the brand names Boncare, Boniva[17], Bondronat, Bonviva, Bandrone, Ibandrix, Adronil, Bondrova, Bonprove, and Fosfonat.

References

  1. ↑ "Bondronat EPAR". 25 June 1996. https://www.ema.europa.eu/en/medicines/human/EPAR/bondronat. 
  2. ↑ "Bonviva EPAR". 23 February 2004. https://www.ema.europa.eu/en/medicines/human/EPAR/bonviva. 
  3. ↑ "Iasibon EPAR". 21 January 2011. https://www.ema.europa.eu/en/medicines/human/EPAR/iasibon. 
  4. ↑ "Ibandronate: the first once-monthly oral bisphosphonate for treatment of postmenopausal osteoporosis". Therapeutics and Clinical Risk Management 2 (1): 3–18. March 2006. PMID 18360577. 
  5. ↑ "National Center for Biotechnology Information (2026). PubChem Compound Summary for CID 23663991, Ibandronate Sodium". https://pubchem.ncbi.nlm.nih.gov/compound/Ibandronate-Sodium.. 
  6. ↑ 6.0 6.1 "Bisphosphonate treatment and dental implants: A systematic review". Medicina Oral, Patologia Oral y Cirugia Bucal 21 (5): e644–e651. September 2016. doi:10.4317/medoral.20920. PMID 27475681. 
  7. ↑ 7.0 7.1 7.2 "Ibandronate: a clinical pharmacological and pharmacokinetic update". Journal of Clinical Pharmacology 44 (9): 951–965. September 2004. doi:10.1177/0091270004267594. PMID 15317823. 
  8. ↑ Analogue-based Drug Discovery. John Wiley & Sons. 2006. pp. 523. ISBN 978-3-527-60749-5. https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA523. 
  9. ↑ "Boniva". The American Society of Health-System Pharmacists. https://www.drugs.com/monograph/boniva.html. 
  10. ↑ "Pathogenesis and bisphosphonate treatment of skeletal events and bone pain in metastatic cancer: focus on ibandronate". Onkologie 35 (6): 380–387. 2012. doi:10.1159/000338947. PMID 22722461. 
  11. ↑ "Information for Healthcare Professionals: Bisphosphonates (marketed as Actonel, Actonel+Ca, Aredia, Boniva, Didronel, Fosamax, Fosamax+D, Reclast, Skelid, and Zometa)". U.S. Food and Drug Administration. https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124165.htm. 
  12. ↑ "Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research". Journal of Bone and Mineral Research 25 (11): 2267–2294. November 2010. doi:10.1002/jbmr.253. PMID 20842676. ; Lay summary in: "JBMR Publishes ASBMR Task Force Report on Atypical Femoral Fractures". Journal of Bone and Mineral Research. 14 September 2010. http://www.asbmr.org/about/pressreleases/detail.aspx?cid=a68f2b70-a117-4094-9f6f-b5993c6a6149. 
  13. ↑ "Osteonecrosis of the jaw (ONJ) and drug treatments for osteoporosis". United Kingdom: The National Osteoporosis Society. https://nos.org.uk/media/1593/k-drug-treatments-for-osteoporosis-osteonecrosis-of-the-jaw-onj-_.pdf. 
  14. ↑ "Cellular and molecular mechanisms of action of bisphosphonates". Cancer 88 (12 Suppl): 2961–2978. June 2000. doi:10.1002/1097-0142(20000615)88:12+<2961::AID-CNCR12>3.0.CO;2-L. PMID 10898340. 
  15. ↑ Essentials of Medical Pharmacology (Seventh ed.). New Delhi: Jaypee Brothers Medical Publisher. 30 September 2013. ISBN 978-93-5025-937-5. OCLC 868299888. 
  16. ↑ 16.0 16.1 "Ibandronate" (in en). PubChem. U.S. National Library of Medicine. https://pubchem.ncbi.nlm.nih.gov/compound/Ibandronate. 
  17. ↑ Townsend, Alain (2020-03). "Vincenzo Cerundolo 1959–2020" (in en). Nature Immunology 21 (3): 243–243. doi:10.1038/s41590-020-0617-5. ISSN 1529-2916. https://www.nature.com/articles/s41590-020-0617-5. 



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