title: The pharmacokinetics and pharmacodynamics of zoledronic acid in cancer patients with varying degrees of renal function.
abstract: An open-label pharmacokinetic and pharmacodynamic study of zoledronic acid (Zometa) was performed in 19 cancer patients with bone metastases and known, varying levels of renal function. Patients were stratified according to creatinine clearance (CLcr) into different groups of normal (CLcr > 80 mL/min), mildly (CLcr = 50-80 mL/min), or moderately/severely impaired (CLcr = 10-50 mL/min) renal function. Three intravenous infusions of 4 mg zoledronic acid were administered at 1-month intervals between doses. Plasma concentrations and amounts excreted in urine were determined in all subjects, and 4 patients were administered 14C-labeled zoledronic acid to assess excretion and distribution of drug in whole blood. In general, the drug was well tolerated by the patients. Mean area under the plasma concentration versus time curve and mean concentration immediately after cessation of drug infusion were lower, and mean amounts excreted in urine over 24 hours from start of infusion were higher in normal subjects than in those with impaired renal function (36% vs. 28% of excreted dose), although the differences were not significant. Furthermore, with repeated doses, there was no evidence of drug accumulation in plasma or changes in drug exposure in any of the groups, nor was there any evidence of changes in renal function status. Serum levels of markers of bone resorption (serum C-telopeptide and N-telopeptide) were noticeably reduced after each dose of zoledronic acid across all three renal groups. It was concluded that in patients with mildly to moderately reduced renal function, dosage adjustment of zoledronic acid is likely not necessary.
authors.affiliation: Department of Clinical Pharmacology, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA.
authors.forename: Andrej
authors.initials: A
authors.lastname: Skerjanec
authors.forename: James
authors.initials: J
authors.lastname: Berenson
authors.forename: ChyiHung
authors.initials: C
authors.lastname: Hsu
authors.forename: Pierre
authors.initials: P
authors.lastname: Major
authors.forename: Wilson H
authors.initials: WH
authors.lastname: Miller
authors.forename: Christina
authors.initials: C
authors.lastname: Ravera
authors.forename: Horst
authors.initials: H
authors.lastname: Schran
authors.forename: John
authors.initials: J
authors.lastname: Seaman
authors.forename: Felix
authors.initials: F
authors.lastname: Waldmeier
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary*; D004164:Diphosphonates / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007677:Kidney Function Tests; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid