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


CONCLUSIONS
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.
Lichtman
Stuart M
SM
Don Monti Division of Medical Oncology, North Shore University Hospital-NYU School of Medicine, 300 Community Drive, Manhasset, NY 11030, USA. slichtma@suffolk.lib.ny.us
Etcubanas
Erlinda
E
Budman
Daniel R
DR
Eisenberg
Peter
P
Zervos
George
G
D'Amico
Paul
P
O'Mara
Vivian
V
Musgrave
Kimberly
K
Cascella
Peter
P
Melikian
Armen
A
Hinderling
Peter H
PH
Ferrer
Jorge M
JM
Williams
Gary J
GJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D003404:Creatinine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011446:Prospective Studies; D001084:Vidarabine Phosphate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology*
D000964:Antimetabolites, Antineoplastic; D001084:Vidarabine Phosphate; C042382:fludarabine phosphate; D003404:Creatinine