| In vitro circuit stability of 5-fluorouracil and oxaliplatin in support of hyperthermic isolated hepatic perfusion. | |
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MedLine Citation:
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PMID: 20437796 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Over the years, a large number of drugs have been used in isolated perfusion of extremities or organs. To interpret the pharmacokinetics of these drugs correctly, the contributions of tissue or organ clearance and chemical degradation, respectively, to overall drug elimination from the circuit need to be identified. In support of a phase I clinical trial of isolated hepatic perfusion (IHP), delivering 5-fluorouracil (5-FU) and oxaliplatin to patients with colorectal cancer hepatic metastases, we aimed to characterize the stability of 5-FU and oxaliplatin in the IHP circuit. Stability of 5-FU and oxaliplatin was assessed in human blood, lactated Ringer infusion (LRI), and in an in vitro IHP circuit consisting of both blood and LRI. Samples were analyzed with liquid chromatography tandem mass spectrometry (5-FU) and atomic absorption spectrophotometry (oxaliplatin). 5-FU was stable under all tested in vitro conditions, but ultrafilterable platinum concentrations decreased slowly with a half-life of 85 minutes in both IHP perfusate and whole blood. The stability of 5-FU in the media containing blood is likely attributable to saturation of dihydropyrimidine dehydrogenase. The decrease of ultrafilterable platinum in blood-containing media with an 85 minutes half-life is in agreement with previous reports on oxaliplatin biotransformation. Oxaliplatin and 5-FU are sufficiently stable in the circuit for the 1-hour perfusion in ongoing and planned clinical trials. |
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Authors:
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Heidi Colville; Ryan Dzadony; Rebecca Kemp; Stephen Stewart; Herbert J Zeh; David L Bartlett; Julianne Holleran; Kevin Schombert; Juliann E Kosovec; Merrill J Egorin; Jan H Beumer |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: The Journal of extra-corporeal technology Volume: 42 ISSN: 0022-1058 ISO Abbreviation: J Extra Corpor Technol Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-05-04 Completed Date: 2010-06-07 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0267637 Medline TA: J Extra Corpor Technol Country: United States |
Other Details:
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Languages: eng Pagination: 75-9 Citation Subset: T |
Affiliation:
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Shadyside Hospital Perfusion Services, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Combined Chemotherapy Protocols
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chemistry* Blood Chemical Analysis* Drug Stability Fluorouracil / chemistry* Humans Hyperthermia, Induced / methods Liver* Organoplatinum Compounds / chemistry* Perfusion / methods |
| Grant Support | |
ID/Acronym/Agency:
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P30 CA047904-219021/CA/NCI NIH HHS; R21 CA115059/CA/NCI NIH HHS; R21 CA115059-02/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Organoplatinum Compounds; 51-21-8/Fluorouracil; 63121-00-6/oxaliplatin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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