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The Pharmacokinetics and Pharmacodynamics of Zoledronic Acid in Cancer Patients with Varying Degrees of Renal Function
Author(s) -
Skerjanec Andrej,
Berenson James,
Hsu ChyiHung,
Major Pierre,
Miller Wilson H.,
Ravera Christina,
Schran Horst,
Seaman John,
Waldmeier Felix
Publication year - 2003
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270002239824
Subject(s) - pharmacokinetics , zoledronic acid , renal function , medicine , n terminal telopeptide , pharmacodynamics , creatinine , urine , bone resorption , urology , endocrinology , renal physiology , pharmacology , chemistry , alkaline phosphatase , osteocalcin , biochemistry , enzyme
An open‐label pharmacokinetic and pharmacodynamic study of zoledronic acid (Zometaθ) was performed in 19 cancer patients with bone metastases and known, varying levels of renal function. Patients were stratified according to creatinine clearance (CL cr ) into different groups of normal (CL cr > 80 mL/min), mildly (CL cr = 50–80 mL/min), or moderately/severely impaired (CL cr = 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 14 C‐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.