Identification | |
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Name | Pamidronate |
Accession Number | DB00282 (APRD01161) |
Type | small molecule |
Description | Pamidronic acid (INN) or pamidronate disodium (USAN), marketed as pamidronate disodium pentahydrate under the brand name Aredia, is a bisphosphonate. [Wikipedia] |
Structure |
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Categories (*) | |
Molecular Weight | 235.0695 |
Groups | approved |
Monoisotopic Weight | 235.001074735 |
Pharmacology | |
Indication | For the treatment of moderate or severe hypercalcemia associated with malignancy |
Mechanism of action | The mechanism of action of pamidronate is inhibition of bone resorption. Pamidronate adsorbs to calcium phosphate (hydroxyapatite) crystals in bone and may directly block dissolution of this mineral component of bone. In vitro studies also suggest that inhibition of osteoclast activity contributes to inhibition of bone resorption. Pamidronate 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 | Plasma concentration rises rapidly upon IV administration. |
Protein binding | Approximately 54% to human serum proteins. |
Biotransformation | Pamidronate is not metabolized and is exclusively eliminated by renal excretion |
Route of elimination | Pamidronate is not metabolized and is exclusively eliminated by renal excretion. |
Toxicity | Side effects include an allergic reaction, kidney problems, seizures, low levels of calcium, magnesium, or phosphorus in the blood |
Affected organisms |
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Interactions | |
Drug Interactions | Not Available |
Food Interactions | Not Available |
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 | 0.6228 |
Hydroxyapatite | |
Name | Hydroxyapatite |
Gene Name | Not Available |
Pharmacological action | yes |
Actions | antagonist |
References |
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DTHybrid score | Not Available |