Drug nameZoledronate
DescriptionZoledronate (zoledronic acid, marketed by Novartis under the trade names Zometa and Reclast) is a bisphosphonate. Zometa is used to prevent skeletal fractures in patients with cancers such as multiple myeloma and prostate cancer. It can also be used to treat hypercalcemia of malignancy and can be helpful for treating pain from bone metastases. An annual dose of Zoledronate may also prevent recurring fractures in patients with a previous hip fracture. Zoledronate is a single 5 mg infusion for the treatment of Paget`s disease of bone. In 2007, the FDA also approved Reclast for the treatment of postmenopausal osteoporosis.
DrugBankPrimary Accession Number: DB00399
DIN02242725
TypeApproved, Small Molecule
IndicationFor the treatment of hypercalcemia of malignancy. Also for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. In May of 2007, the drug was approved for treatment of Paget’s Disease.
Mechanism of ActionThe action of zoledronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Zoledronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates such as 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.
AbsorptionPoorly absorbed (oral absorption is about 1% of what intravenous absorption is).
ToxicityThere is no experience of acute overdose. Two patients received zoledronate (32 mg) over 5 minutes in clinical trials. Neither patient experienced any clinical or laboratory toxicity. Overdosage may cause clinically significant hypocalcemia, hypophosphatemia, and hypomagnesemia.
Protein BindingApproximately 22% bound in human plasma, independent of the concentration. However, Canadian product information states binding to human plasma protein is approximately 56%.
Interactions
RXListhttp://www.rxlist.com/cgi/generic/zometa.htm
KEGGdrug: D01968 / compound: Not Available
PubChemcompound: 68740 / substance: 536160
PharmGKBPA10235
Metabolizing Enzymes
NameGeneEntrezIDUniprotSNP
Target
NameGeneEntrezIDSwissprotSNP
Farnesyl pyrophosphate synthetaseFDPS2224FPPS_HUMANrs41314549 rs35362111 rs16836822 rs16836819 rs12407073 rs11556437 rs11556436 rs11556434 rs11556433 rs11556432 rs2229578 rs2148136 rs1050365 rs17456
FilesDB00399.mol | DB00399_622.pdf | pdb_243188801309-0.pdb | sdf_5353878214996-0.sdf |
Smilesisomeric:
OC(CN1C=CN=C1)(P(O)(O)=O)P(O)(O)=O
canonical:
OC(CN1C=CN=C1)(P(O)(O)=O)P(O)(O)=O

© 2010-2020 All rights reserved. King Abdullah University of Science and Technology, All rights reserved