Titre
Pharmacokinetics of pamidronate in patients with bone metastases
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Leyvraz, S.
Auteure/Auteur
Hess, U.
Auteure/Auteur
Flesch, G.
Auteure/Auteur
Bauer, J.
Auteure/Auteur
Hauffe, S.
Auteure/Auteur
Ford, J. M.
Auteure/Auteur
Burckhardt, P.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0027-8874
Statut éditorial
Publié
Date de publication
1992-05
Volume
84
Numéro
10
Première page
788
Dernière page/numéro d’article
92
Notes
Journal Article --- Old month value: May 20
Résumé
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.
Sujets
PID Serval
serval:BIB_69F252EB00C4
PMID
Open Access
Oui
Date de création
2008-01-28T07:32:01.050Z
Date de création dans IRIS
2025-05-20T23:56:42Z
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Nom
REF.pdf
Version du manuscrit
published
Taille
2.23 MB
Format
Adobe PDF
PID Serval
serval:BIB_69F252EB00C4.P001
URN
urn:nbn:ch:serval-BIB_69F252EB00C44
Somme de contrôle
(MD5):5238f01d76e05d0769aa8d5cc0b20b8f