Pharmacokinetics of pamidronate in patients with bone metastases

Details

Ressource 1Download: serval:BIB_69F252EB00C4.P001 (2282.88 [Ko])
State: Public
Version: author
License: Not specified
It was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
Serval ID
serval:BIB_69F252EB00C4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Pharmacokinetics of pamidronate in patients with bone metastases
Journal
Journal of the National Cancer Institute
Author(s)
Leyvraz  S., Hess  U., Flesch  G., Bauer  J., Hauffe  S., Ford  J. M., Burckhardt  P.
ISSN
0027-8874 (Print)
Publication state
Published
Issued date
05/1992
Volume
84
Number
10
Pages
788-92
Notes
Journal Article --- Old month value: May 20
Abstract
BACKGROUND: Pamidronate is a second-generation bisphosphonate used in the treatment of tumor-induced hypercalcemia and in the management of bone metastases from breast cancer, myeloma, or prostate cancer. The pharmacokinetics of pamidronate is unknown in cancer patients. PURPOSE: To determine the influence of the rate of administration and of bone metabolism, we studied the pharmacokinetics of pamidronate at three different infusion rates in 37 patients with bone metastases. METHODS: Three groups of 11-14 patients were given 60 mg pamidronate as an intravenous infusion over a period of 1, 4, or 24 hours. Urine samples were collected in the three groups of patients. Plasma samples were obtained only in the 1-hour infusion group. The assay of pamidronate in plasma and urine was performed by high-performance liquid chromatography with fluorescence detection after the derivatization of pamidronate with fluorescamine. RESULTS: The body retention (BR) at 0-24 hours of pamidronate represented 60%-70% of the administered dose and was not significantly modified by the infusion rate. In particular, the BR at 0-24 hours was not reduced at the fastest infusion rate. Among patients, a threefold variability in BR at 0-24 hours occurred, which was related directly to the number of bone metastases and, to some extent, to creatinine clearance. At 60 mg/hour, the plasma kinetics followed a multiexponential course characterized by a short distribution phase. The mean (+/- SD) half-life of the distribution phase was 0.8 hour (+/- 0.3), the mean (+/- SD) of the area under the curve for drug concentration in plasma x time at 0-24 hours was 22.0 +/- 8.8 mumol/L x hours, and the mean (+/- SD) of the maximum plasma concentration was 9.7 mumol/L (+/- 3.2). Pharmacokinetic variables remained unchanged after repeated infusions applied to four patients. Clinically, the three infusion rates were equally well tolerated without significant toxicity. CONCLUSIONS: The 1-hour infusion rate could be proposed as kinetically appropriate for the administration of pamidronate to patients with metastatic bone diseases.
Keywords
Aged Aged, 80 and over Bone Neoplasms/blood/*metabolism/*secondary/urine Diphosphonates/administration & dosage/blood/*pharmacokinetics/urine Female Humans Male Middle Aged
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 8:32
Last modification date
01/10/2019 6:18
Usage data