Fludarabine: pharmacokinetics, mechanisms of action, and rationales for combination therapies.

Abstract:

: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.

journal_name

Semin Oncol

journal_title

Seminars in oncology

authors

Plunkett W,Gandhi V,Huang P,Robertson LE,Yang LY,Gregoire V,Estey E,Keating MJ

subject

Has Abstract

pub_date

1993-10-01 00:00:00

pages

2-12

issue

5 Suppl 7

eissn

0093-7754

issn

1532-8708

journal_volume

20

pub_type

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