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.
University of Mississippi Medical Center, Jackson, MS, USA.
Sharon
S
Lobert
Christian
C
Puozzo
D000367:Age Factors; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D004347:Drug Interactions; D006801:Humans; D008870:Microtubules / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D050257:Tubulin Modulators / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D014747:Vinblastine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D050257:Tubulin Modulators; C111217:vinflunine; D014747:Vinblastine