The pharmacokinetics and pharmacodynamics of fludarabine phosphate in patients with renal impairment: a prospective dose adjustment study.

Abstract

UNLABELLED:

A significant number of chronic lymphocytic leukemia, follicular non-Hodgkin's lymphoma and Waldenström's macroglobulinemia patients, treated with fludarabine phosphate (fludarabine), are elderly with diminished renal function. Since the kidney eliminates approximately 60% of fludarabine's primary metabolite (F-ara-A), dose modification is necessary for all patients with impaired renal function including elderly patients. In this study, 22 patients with varying levels of renal function received a single intravenous dose of fludarabine (25 mg/m3), followed one week later by five (one per day) doses that were adjusted according to three predefined creatinine clearance (CLcr) levels. Relationships between renal function and F-ara-A clearance, F-ara-A exposure and F-ara-A--related toxicities were examined. The results demonstrate that total F-ara-A clearance correlated with CLcr and that F-ara-A exposure levels and patient toxicity profiles were similar across treatment groups.

IN CONCLUSION:

The CLcr-based fludarabine dose adjustments used in this study provided reasonably equivalent F-ara-A exposure with acceptable safety in patients with varying degrees of renal function.

• Authors: Stuart M Lichtman, Erlinda Etcubanas, Daniel R Budman, Peter Eisenberg, George Zervos, Paul D'Amico, Vivian O'Mara, Kimberly Musgrave, Peter Cascella, Armen Melikian, Peter H Hinderling, Jorge M Ferrer, Gary J Williams
• Journal: Cancer investigation (Cancer Invest) Vol. 20 Issue 7-8 Pg. 904-13 ( 2002) ISSN: 0735-7907 [Print] England
• PMID: 12449721 (Publication Type: Comparative Study, Journal Article, Multicenter Study)

Chemical References

• Antimetabolites, Antineoplastic
• Vidarabine Phosphate
• fludarabine phosphate
• Creatinine

Topics

• Adult
• Aged
• Aged, 80 and over
• Antimetabolites, Antineoplastic (pharmacokinetics, pharmacology)
• Area Under Curve
• Creatinine (metabolism)
• Dose-Response Relationship, Drug
• Female
• Humans
• Injections, Intravenous
• Kidney Failure, Chronic (metabolism)
• Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy, metabolism)
• Lymphoma, Non-Hodgkin (drug therapy, metabolism)
• Male
• Metabolic Clearance Rate
• Middle Aged
• Prospective Studies
• Vidarabine Phosphate (analogs & derivatives, pharmacokinetics, pharmacology)