DT-Web

DB00710 - Ibandronate


Identification
Name Ibandronate
Accession Number DB00710 (APRD00231, DB04635)
Type small molecule
Description Ibandronate is a nitrogen-containing bisphosphonate in the same class as alendronate and risedronate. Ibandronate inhibits osteoclast-mediated bone resorption. All of the bisphosphonates prevent the breakdown of bone by bone cells called osteoclasts. In persons who are at high risk for osteoporosis, bisphosphonates not only result in increased amounts of bone and bone strength, they also reduce the risk of hip fractures and other bone fractures.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 319.2289
Groups approved
Monoisotopic Weight 319.094975119
Pharmacology
Indication For the treatment and prevention of osteoporosis in postmenopausal women.
Mechanism of action The action of ibandronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting farnesyl pyrophosphate (FPP) synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.
Absorption Poorly absorbed (mean bioavailability following a 2.5 mg oral dose is about 0.6% compared to intravenous dosing). Absorption is impaired by any kind of food or drink other than plain water.
Protein binding 90.9 to 99.5% over an ibandronate concentration range of 2 to 10 ng/mL
Biotransformation No evidence of ibandronate being metabolized in humans.
Route of elimination Ibandronate is eliminated by renal excretion. Unabsorbed ibandronate is eliminated unchanged in the feces.
Toxicity LD50 = 811 mg/kg (rat, oral), side effects include bronchitis, pneumonia and urinary tract infections.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Aluminium Formation of non absorbable complexes
Calcium Formation of non-absorbable complexes
Calcium Acetate Calcium Salts may decrease the serum concentration of Bisphosphonate Derivatives such as ibandronate. Avoid administration of oral calcium supplements within 60 minutes after oral ibandronate.
Calcium Chloride Calcium salts may decrease the serum concentration of bisphosphonate derivatives. Avoid administration of oral calcium supplements within 60 minutes after oral ibandronate.
Iron Formation of non absorbable complexes
Iron Dextran Formation of non-absorbable complexes
Magnesium Formation of non-absorbable complexes
Magnesium oxide Formation of non absorbable complexes
Sucralfate Formation of non absorbable complexes
Food Interactions
  • Take on an empty stomach. All foods markedly reduce (up to 90%) ibandronate bioavailabilty. Take with plain water (not mineralized) at least 1 hour before any food. Bioavailability and effect on bone density are both impaired if the patient eats or drinks in less than 1 hour after taking this product. Drink a large glass of water and stay in an upright position for at least 60 minutes after taking this product.

Targets


Farnesyl pyrophosphate synthetase
Name Farnesyl pyrophosphate synthetase
Gene Name FDPS
Pharmacological action yes
Actions inhibitor
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Chapurlat RD, Delmas PD: Drug insight: Bisphosphonates for postmenopausal osteoporosis. Nat Clin Pract Endocrinol Metab. 2006 Apr;2(4):211-9; quiz following 238. - Pubmed
  • Dunford JE, Thompson K, Coxon FP, Luckman SP, Hahn FM, Poulter CD, Ebetino FH, Rogers MJ: 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. - Pubmed
  • Rondeau JM, Bitsch F, Bourgier E, Geiser M, Hemmig R, Kroemer M, Lehmann S, Ramage P, Rieffel S, Strauss A, Green JR, Jahnke W: Structural basis for the exceptional in vivo efficacy of bisphosphonate drugs. ChemMedChem. 2006 Feb;1(2):267-73. - Pubmed
DTHybrid score 0.6228
Hydroxyapatite
Name Hydroxyapatite
Gene Name Not Available
Pharmacological action yes
Actions antagonist
References
  • Jahnke W, Henry C: An in vitro assay to measure targeted drug delivery to bone mineral. ChemMedChem. 2010 May 3;5(5):770-6. - Pubmed
  • Nancollas GH, Tang R, Phipps RJ, Henneman Z, Gulde S, Wu W, Mangood A, Russell RG, Ebetino FH: Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone. 2006 May;38(5):617-27. Epub 2005 Jul 20. - Pubmed
DTHybrid score Not Available

Predictions


Id Partner name Gene Name Score
6058 Geranylgeranyl pyrophosphate synthetase GGPS1 0.1179
6548 4-hydroxy-3-methylbut-2-enyl diphosphate reductase ispH 0.097
6547 Isopentenyl-diphosphate Delta-isomerase 1 IDI1 0.0696
6647 Geranyltranstransferase (Farnesyldiphosphate synthase) ispA 0.0522
6596 Short-chain Z-isoprenyl diphosphate synthetase Rv1086 0.0423
5744 Undecaprenyl pyrophosphate synthetase uppS 0.0421
2756 Geranyltranstransferase ispA 0.042
6056 Receptor-type tyrosine-protein phosphatase epsilon PTPRE 0.0369
1376 Tyrosine-protein phosphatase non-receptor type 4 PTPN4 0.0369
6576 Geranylgeranyl transferase type-2 subunit beta RABGGTB 0.0365
6575 Geranylgeranyl transferase type-2 subunit alpha RABGGTA 0.0365
290 Prostaglandin G/H synthase 2 PTGS2 0.0349
4284 Pentaerythritol tetranitrate reductase onr 0.0348
6055 Receptor-type tyrosine-protein phosphatase S PTPRS 0.0322
4128 Protein farnesyltransferase subunit beta FNTB 0.0305
6057 V-type proton ATPase catalytic subunit A ATP6V1A 0.0301
4129 Protein farnesyltransferase/geranylgeranyltransferase type I alpha subunit FNTA 0.0299
3188 IspD/ispF bifunctional enzyme [Includes: 2-C-methyl-D-erythritol 4- phosphate cytidylyltransferase ispDF 0.0259
862 Multidrug resistance-associated protein 1 ABCC1 0.024
1994 Geranylgeranyl transferase type-1 subunit beta PGGT1B 0.0237
6540 Prenyltransferase Not Available 0.0224
2383 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase ispF 0.0208
2937 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase ispF 0.0208
4620 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase ispF 0.0208
6594 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase ispF 0.0208
6609 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase ispF 0.0208
6646 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase ispF 0.0208
6595 Lantibiotic nisin-Z nisZ 0.0189
6574 GTPase KRas KRAS 0.0151
↑