Pharmacokinetics, Metabolites, and Preclinical Safety of Vinflunine
The novel microtubule inhibitor, vinflunine, has a unique mechanism of action that differs from other members of the vinca alkaloid class in terms of tubulin-binding affinity, microtubule dynamics, spiral formation, and intracellular accumulation. Vinflunine has shown significant activity in vivo, which involves its antimitotic, antiangiogenic, and antivascular properties. The promising preclinical activity of vinflunine has warranted further investigation in the clinical setting. This review explores the distinct interaction of vinflunine with its intracellular targets to gain insight into its mechanism of action and safety profile. The pharmacokinetic properties and metabolism of vinflunine in animals and in human subjects are also discussed, together with an analysis of potential drug-drug interactions and the influence of age, liver dysfunction, or renal dysfunction on the overall activity of vinflunine.
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Dr Lobert has received consulting fees from Bristol-Myers Squibb and has received research support from Pierre Fabre Oncologie. Dr Puozzo is an employee of the Institut de Recherche Pierre Fabre, a private pharmaceutical company supporting the development of vinflunine.
PII: S0093-7754(08)00020-1
doi:10.1053/j.seminoncol.2008.01.007
© 2008 Elsevier Inc. All rights reserved.
