title: Zoledronic acid: a new parenteral bisphosphonate.
abstract: BACKGROUND
  Inhibition of bone resorption using bisphosphonates is an important step in palliation of complications of advanced cancer, such as hypercalcemia and metastatic bone disease.
  
  
  OBJECTIVE
  The goal of this article was to describe the pharmacologic properties of zoledronic acid (zoledronate) and discuss findings from preclinical and clinical studies of its use in skeletal disorders.
  
  
  METHODS
  Relevant English-language literature was identified using the terms zoledronic acid, zoledronate, Zometa, and 118072-93-8 through searches of MEDLINE (1966-June 2003) and International Pharmaceutical Abstracts (1970-June 2003), and abstract proceedings from the American Society of Clinical Oncology (1997-2002).
  
  
  RESULTS
  Zoledronic acid is a nitrogen-containing bisphosphonate that inhibits bone resorption. It is indicated for the treatment of hypercalcemia of malignancy and for the treatment of patients with multiple myeloma or documented metastasis from solid tumors, in conjunction with standard antineoplastic therapy. The recommended dosage is 4 mg via IV over >or= 15 minutes every 3 or 4 weeks. Compared with pamidronate 90 mg, zoledronic acid 4 and 8 mg provided a higher complete response rate for hypercalcemia of malignancy by day 10 (88.4% and 86.7% vs 69.7%; P = 0.002 and P = 0.015) and longer duration of action (median time to relapse, 30 and 40 days vs 17 days; P = 0.001 and P = 0.007). In patients with breast cancer or multiple myeloma, zoledronic acid was as effective as pamidronate in delaying time to a first skeletal-related event (373 days vs 363 days). In patients with hormone-refractory prostate cancer and bone metastases, zoledronic acid 4 mg reduced the proportion of patients who experienced a skeletal-related event (33% vs 44% with placebo; P = 0.021) or a skeletal fracture (13% vs 22% with placebo; P = 0.015). In patients with bone metastases from solid tumors, zoledronic acid delayed the median time to a first skeletal-related event (230 days vs 163 days with placebo; P = 0.023). Common adverse events include fever, nausea, constipation, fatigue, and bone pain.
  
  
  CONCLUSIONS
  Zoledronic acid is an effective and generally well-tolerated treatment for hypercalcemia of malignancy and skeletal complications of metastatic bone disease.
authors.affiliation: Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Li
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Davis
mesh_terms: D000818:Animals; D001851:Bone Diseases, Metabolic / Q000188:drug therapy; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D002986:Clinical Trials as Topic; D004164:Diphosphonates / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D006207:Half-Life; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy / Q000209:etiology; D007093:Imidazoles / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D008657:Metabolic Clearance Rate; D009369:Neoplasms / Q000150:complications; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid