| Preclinical evaluation of novel, all-in-one formulations of 5-fluorouracil and folinic acid with reduced toxicity profiles. | |
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MedLine Citation:
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PMID: 20881836 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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5-Fluorouracil (5-FU) in combination with its synergistic biomodulator folinic acid maintains a pivotal position in cancer chemotherapy. However, clinical limitations such as phlebitis and catheter blockages persist with the administration of these drugs in combination, and are associated with reduced efficacy and/or quality of life for patients. We have reported earlier on the novel, all-in-one, pH neutral, parenteral 5-FU and folinic acid formulations (termed Fluorodex) incorporating β-cyclodextrins. Fluorodex maintains potency while overcoming the accepted incompatibility of 5-FU and folinic acid. We carried out toxicological, pharmacokinetic and biodistribution, and efficacy evaluations of Fluorodex compared with 5-FU:folinic acid using several administration routes and schedules in two rodent models. These were compared with the dose-matched sequential administration of 5-FU:folinic acid. Fluorodex showed bioequivalence to 5-FU:folinic acid as assessed by the tissue distribution and pharmacokinetic studies of 5-FU, but was generally better tolerated as determined by weight loss, hematological, and other clinical parameters. Compared with 5-FU:folinic acid, Fluorodex was also associated with reduced phlebitis using a rabbit ear vein model. Furthermore, using human carcinoma tumor models in mice, Fluorodex resulted in equivalent or improved efficacy profiles compared with 5-FU:folinic acid. In conclusion, these novel, all-in-one formulations represent a superior injectable form of 5-FU that allows codelivery of folinic acid. This should translate into improved patient tolerability with potential for enhanced efficacy. |
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Authors:
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Tamantha K Stutchbury; Kara L Vine; Julie M Locke; Jeremy S Chrisp; John B Bremner; Philip R Clingan; Marie Ranson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Anti-cancer drugs Volume: 22 ISSN: 1473-5741 ISO Abbreviation: Anticancer Drugs Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-11-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9100823 Medline TA: Anticancer Drugs Country: England |
Other Details:
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Languages: eng Pagination: 24-34 Citation Subset: IM |
Affiliation:
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School of Biological Sciences, Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW 2522, Australia. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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