DB00630 - Alendronate
| Identification | |||||||||||||||||||||||||||||||||||||||||||
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| Name | Alendronate | ||||||||||||||||||||||||||||||||||||||||||
| Accession Number | DB00630 (APRD00561) | ||||||||||||||||||||||||||||||||||||||||||
| Type | small molecule | ||||||||||||||||||||||||||||||||||||||||||
| Description | Alendronate is a nitrogen-containing, second generation bisphosphonate. Bisphosphonates were first used to treat Paget's disease in 1971. This class of medications is comprised of inorganic pyrophosphate analogues that contain non-hydrolyzable P-C-P bonds. Similar to other bisphosphonates, alendronate has a high affinity for bone mineral and is taken up during osteoclast resorption. Alendronate inhibits farnesyl pyrophosphate synthetase, one of the enzymes in the mevalonic acid pathway involved in producing isoprenoid compounds that are essential for post-translational modification of small guanosine triphosphate (GTP)-binding proteins, such as Rho, Ras and Rab. Inhibition of this process interferes with osteoclast function and survival. Alendronate is used for the treatment of osteoporosis and Paget's disease. | ||||||||||||||||||||||||||||||||||||||||||
| Structure |
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| Categories (*) | |||||||||||||||||||||||||||||||||||||||||||
| Molecular Weight | 249.096 | ||||||||||||||||||||||||||||||||||||||||||
| Groups | approved | ||||||||||||||||||||||||||||||||||||||||||
| Monoisotopic Weight | 249.016724799 | ||||||||||||||||||||||||||||||||||||||||||
| Pharmacology | |||||||||||||||||||||||||||||||||||||||||||
| Indication | For the treatment and prevention of osteoporosis in women and Paget's disease of bone in both men and women. | ||||||||||||||||||||||||||||||||||||||||||
| Mechanism of action | The action of Alendronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Alendronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting 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 | Relative to an intravenous (IV) reference dose, the mean oral bioavailability of alendronate in women was 0.7% for doses ranging from 5 to 40 mg when administered after an overnight fast and two hours before a standardized breakfast. Oral bioavailability of the 10 mg tablet in men (0.59%) was similar to that in women (0.78%) when administered after an overnight fast and 2 hours before breakfast. | ||||||||||||||||||||||||||||||||||||||||||
| Protein binding | 78% | ||||||||||||||||||||||||||||||||||||||||||
| Biotransformation | There is no evidence that alendronate is metabolized in humans or animals. | ||||||||||||||||||||||||||||||||||||||||||
| Route of elimination | Following a single IV dose of [14C]alendronate, approximately 50% of the radioactivity was excreted in the urine within 72 hours and little or no radioactivity was recovered in the feces. | ||||||||||||||||||||||||||||||||||||||||||
| Toxicity | Alendronate can damage the esophagus both by toxicity from the medication itself and by nonspecific irritation secondary to contact between the pill and the esophageal mucosa, similar to other cases of "pill esophagitis." | ||||||||||||||||||||||||||||||||||||||||||
| Affected organisms |
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| Interactions | |||||||||||||||||||||||||||||||||||||||||||
| Drug Interactions |
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| Food Interactions |
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Targets
| Farnesyl pyrophosphate synthetase | |
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| Name | Farnesyl pyrophosphate synthetase |
| Gene Name | FDPS |
| Pharmacological action | yes |
| Actions | inhibitor |
| References |
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| DTHybrid score | 1.0718 |
| Hydroxyapatite | |
| Name | Hydroxyapatite |
| Gene Name | Not Available |
| Pharmacological action | yes |
| Actions | antagonist |
| References |
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| DTHybrid score | Not Available |
| Tyrosine-protein phosphatase non-receptor type 4 | |
| Name | Tyrosine-protein phosphatase non-receptor type 4 |
| Gene Name | PTPN4 |
| Pharmacological action | unknown |
| Actions | inhibitor |
| References |
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| DTHybrid score | 1.0504 |
| Receptor-type tyrosine-protein phosphatase S | |
| Name | Receptor-type tyrosine-protein phosphatase S |
| Gene Name | PTPRS |
| Pharmacological action | unknown |
| Actions | inhibitor |
| References |
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| DTHybrid score | 1.5317 |
| Receptor-type tyrosine-protein phosphatase epsilon | |
| Name | Receptor-type tyrosine-protein phosphatase epsilon |
| Gene Name | PTPRE |
| Pharmacological action | unknown |
| Actions | inhibitor |
| References |
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| DTHybrid score | 1.0508 |
| V-type proton ATPase catalytic subunit A | |
| Name | V-type proton ATPase catalytic subunit A |
| Gene Name | ATP6V1A |
| Pharmacological action | unknown |
| Actions | inhibitor |
| References |
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| DTHybrid score | 2.1754 |