Pamidronic acid

Pamidronic acid or pamidronate disodium or APD (marketed as Aredia among others), is a nitrogen-containing bisphosphonate used to prevent osteoporosis.

Pamidronic acid

Clinical data
Trade names	Aredia, Pamimed, among others
Other names	Pamidronate disodium pentahydrate, pamidronate disodium
AHFS/Drugs.com	International Drug Names
MedlinePlus	a601163
Pregnancy category	AU: B3
Routes of administration	Intravenous
ATC code	M05BA03 (WHO)
Legal status
Legal status	UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	n/a
Protein binding	54%
Metabolism	Nil
Elimination half-life	28 ± 7 hours
Excretion	Renal
Identifiers
IUPAC name (3-amino-1-hydroxypropane-1,1-diyl)bis(phosphonic acid)
CAS Number	40391-99-9^Y
PubChem CID	4674
IUPHAR/BPS	7259
DrugBank	DB00282^Y
ChemSpider	4512^Y
UNII	OYY3447OMC
KEGG	D07281^Y
ChEMBL	ChEMBL834^Y
CompTox Dashboard (EPA)	DTXSID4023414
ECHA InfoCard	100.049.897
Chemical and physical data
Formula	C3H11NO7P2
Molar mass	235.069 g·mol^−1
3D model (JSmol)	Interactive image
SMILES O=P(O)(O)C(O)(CCN)P(=O)(O)O
InChI InChI=1S/C3H11NO7P2/c4-2-1-3(5,12(6,7)8)13(9,10)11/h5H,1-2,4H2,(H2,6,7,8)(H2,9,10,11)^Y Key:WRUUGTRCQOWXEG-UHFFFAOYSA-N^Y
(verify)

It was patented in 1971 and approved for medical use in 1987.^[1]

Medical uses

It is used to prevent bone loss, and treat osteoporosis. It is also used to strengthen bone in Paget's disease, to prevent bone loss due to steroid use, and in certain cancers with high propensity to bone, such as multiple myeloma. Due to its ability to sequester calcium in bone, it is also used to treat high calcium levels. It is also used as an experimental treatment of the bone disorder osteogenesis imperfecta. It has been studied in the treatment of complex regional pain syndrome.^[2]

Administration

Intravenous, usually 90 mg monthly. 30 mg, 60 mg, 90 mg and for hospitals, 120 mg vials are available, mixed with mannitol.

Side effects

Common side effects include bone pain, low calcium levels, nausea, and dizziness. Osteonecrosis of the jaw is a rare complication which has been associated with the use of bisphosphonates, including pamidronate.^[3]

Pamidronate activates human γδ T cells in vitro and in vivo, which may lead to flu-like symptoms upon administration.

Pharmacology

Relative potency^[4]

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

References

1. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 523. ISBN 9783527607495.
2. Kubalek I, Fain O, Paries J, Kettaneh A, Thomas M (December 2001). "Treatment of reflex sympathetic dystrophy with pamidronate: 29 cases". Rheumatology. 40 (12): 1394–1397. doi:10.1093/rheumatology/40.12.1394. PMID 11752511.
3. Zarychanski R, Elphee E, Walton P, Johnston J (January 2006). "Osteonecrosis of the jaw associated with pamidronate therapy". American Journal of Hematology. 81 (1): 73–75. doi:10.1002/ajh.20481. PMID 16369966. S2CID 11830192.
4. Tripathi KD (2013-09-30). Essentials of medical pharmacology (Seventh ed.). New Delhi: Jaypee Brothers Medical Publishers Pvt. Limited. ISBN 9789350259375. OCLC 868299888.