Fludarabine: pharmacokinetics, mechanisms of action, and rationales for combination therapies.
Knowledge of the pharmacokinetics of a drug is essential to the optimal design of the dose and schedule of chemotherapy protocols. As an extension, an understanding of the mechanism of drug action is necessary to construct the optimal strategy for combination chemotherapy. Nucleoside antimetabolites such as fludarabine are pro-drugs that must enter cells and be phosphorylated to the nucleoside triphosphate before they can elicit biologic activity. Thus, knowledge of the pharmacokinetics of the triphosphate in target cells and an understanding of the mechanisms by which this active form of the drug act are indispensable to the rational design of treatment protocols. This article reviews the essential elements of the pharmacokinetics and mechanisms of action of fludarabine to provide a rationale for combinations of fludarabine with other chemotherapeutic agents and anti-cancer modalities.
Plunkett
W
W
Department of Clinical Investigation, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Gandhi
V
V
Huang
P
P
Robertson
L E
LE
Yang
L Y
LY
Gregoire
V
V
Estey
E
E
Keating
M J
MJ
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
D000970:Antineoplastic Agents; D014740:Vidarabine; C024352:fludarabine