Document Detail


Development and validation of a limited sampling strategy for 5-fluorouracil given by bolus intravenous administration.
MedLine Citation:
PMID:  8249045     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A wide range of interindividual variability of 5-fluorouracil (5-FU) pharmacokinetics exists after bolus administration. The degree to which this variability in 5-FU exposure impacts upon the response and toxicity of the drug has not been determined. The area under the concentration time curve (AUC) is a commonly used indicator of exposure, but normally requires the collection of 8-10 timed blood samples after i.v. bolus administration. This presents difficulties if large-scale population samplings are required. This study involved the development and testing of a strategy to estimate AUC from a limited number of blood samples in patients with gastrointestinal and breast cancer. The optimal single time point for AUC estimation was 0.17 h (r2 = 0.954). Addition of the 0.75 h time point significantly improved predictability (r2 = 0.983). Addition of a third or fourth time point did not provide further benefit. These models were then tested separately in a group of women who received a higher dose of 5-FU. The two data points model performed significantly better than the single time point model (r2 = 0.70 and 0.85, respectively). The AUC of standard dose 5-FU after bolus administration can be reliably estimated from two timed samples taken 10 and 45 min after injection.
Authors:
M J Moore; P Bunting; S Yuan; J J Thiessen
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Therapeutic drug monitoring     Volume:  15     ISSN:  0163-4356     ISO Abbreviation:  Ther Drug Monit     Publication Date:  1993 Oct 
Date Detail:
Created Date:  1994-01-06     Completed Date:  1994-01-06     Revised Date:  2006-04-24    
Medline Journal Info:
Nlm Unique ID:  7909660     Medline TA:  Ther Drug Monit     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  394-9     Citation Subset:  IM    
Affiliation:
Department of Medicine, Princess Margaret Hospital, University of Toronto, Canada.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Breast Neoplasms / blood,  drug therapy
Chemotherapy, Adjuvant
Cyclophosphamide / administration & dosage
Female
Fluorouracil / administration & dosage,  blood,  pharmacokinetics*
Humans
Injections, Intravenous
Methotrexate / administration & dosage
Middle Aged
Models, Biological*
Reproducibility of Results
Chemical
Reg. No./Substance:
50-18-0/Cyclophosphamide; 51-21-8/Fluorouracil; 59-05-2/Methotrexate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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