Pharmacokinetics of pamidronate in patients with bone metastases.
J Natl Cancer Inst
; 84(10): 788-92, 1992 May 20.
Article
in En
| MEDLINE
| ID: mdl-1573666
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bone Neoplasms
/
Diphosphonates
Type of study:
Prognostic_studies
Limits:
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
J Natl Cancer Inst
Year:
1992
Type:
Article
Affiliation country:
Switzerland